Solving the muon g -2 anomaly in deflected anomaly mediated SUSY breaking with messenger-matter interactions

NASA Astrophysics Data System (ADS)

Wang, Fei; Wang, Wenyu; Yang, Jin Min

2017-10-01

We propose to introduce general messenger-matter interactions in the deflected anomaly mediated supersymmetry (SUSY) breaking (AMSB) scenario to explain the gμ-2 anomaly. Scenarios with complete or incomplete grand unified theory (GUT) multiplet messengers are discussed, respectively. The introduction of incomplete GUT mulitiplets can be advantageous in various aspects. We found that the gμ-2 anomaly can be solved in both scenarios under current constraints including the gluino mass bounds, while the scenarios with incomplete GUT representation messengers are more favored by the gμ-2 data. We also found that the gluino is upper bounded by about 2.5 TeV (2.0 TeV) in scenario A and 3.0 TeV (2.7 TeV) in scenario B if the generalized deflected AMSB scenarios are used to fully account for the gμ-2 anomaly at 3 σ (2 σ ) level. Such a gluino should be accessible in the future LHC searches. Dark matter (DM) constraints, including DM relic density and direct detection bounds, favor scenario B with incomplete GUT multiplets. Much of the allowed parameter space for scenario B could be covered by the future DM direct detection experiments.

Interindividual Variability in Metabolism of [6]-Shogaol by Gut Microbiota.

PubMed

Wang, Pei; Wang, Ronghui; Zhu, Yingdong; Sang, Shengmin

2017-11-08

[6]-Shogaol (6S), one of the major bioactive components in dry ginger, is attracting considerable attention because of its wide spectrum of biological activities, but its metabolic fate is still not fully understood. In the present study, the microbial metabolism of 6S was examined for the first time in in vitro batch fecal fermentation system and in mice. Two major microbial metabolites were detected and identified as 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9) and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11). Our results indicated that reductions of the double bond and the ketone group are the major metabolic pathways of 6S by the human gut microbiota. We also observed the interindividual variability in the metabolism of M11 to M9 by human gut microbiota. In addition, we demonstrated that the glucuronidated form of 6S and its metabolites could be rapidly deconjugated by human gut microbiota and in mice, which can be regarded as a reactive process taking place in the intestinal tract. To our knowledge, this is the first report involving the identification of the microbial metabolites of 6S in an in vitro fermentation system, and the first demonstration of the critical role of gut microbiota in producing the bioactive free form of 6S and its metabolites in the intestinal tract in mice.

SU(6) GUT breaking on a projective plane

NASA Astrophysics Data System (ADS)

Anandakrishnan, Archana; Raby, Stuart

2013-03-01

We consider a 6-dimensional supersymmetric SU(6) gauge theory and compactify two extra-dimensions on a multiply-connected manifold with non-trivial topology. The SU(6) is broken down to the Standard Model gauge groups in two steps by an orbifold projection, followed by a Wilson line. The Higgs doublets of the low energy electroweak theory come from a chiral adjoint of SU(6). We thus have gauge-Higgs unification. The three families of the Standard Model can either be located in the 6D bulk or at 4D N=1 supersymmetric fixed points. We calculate the Kaluza-Klein spectrum of states arising as a result of the orbifolding. We also calculate the threshold corrections to the coupling constants due to this tower of states at the lowest compactification scale. We study the regions of parameter space of this model where the threshold corrections are consistent with low energy physics. We find that the couplings receive only logarithmic corrections at all scales. This feature can be attributed to the large N=2 6D SUSY of the underlying model.

Roadmap of left-right models based on GUTs

NASA Astrophysics Data System (ADS)

Chakrabortty, Joydeep; Maji, Rinku; Patra, Sunando Kumar; Srivastava, Tripurari; Mohanty, Subhendra

2018-05-01

We perform a detailed study of the grand unified theories S O (10 ) and E (6 ) with left-right intermediate gauge symmetries of the form S U (N )L⊗S U (N )R⊗G . Proton decay lifetime constrains the unification scale to be ≳1016 GeV and, as discussed in this paper, unwanted cosmological relics can be evaded if the intermediate symmetry scale is ≳1012 GeV . With these conditions, we study the renormalization group evolution of the gauge couplings and do a comparative analysis of all possible left-right models where unification can occur. Both the D-parity conserved and broken scenarios as well as the supersymmetric (SUSY) and nonsupersymmetric (non-SUSY) versions are considered. In addition to the fermion and scalar representations at each stage of the symmetry breaking, contributing to the β functions, we list the intermediate left-right groups that successfully meet these requirements. We make use of the dimension-5 kinetic mixing effective operators for achieving unification and large intermediate scale. A significant result in the supersymmetric case is that to achieve successful unification for some breaking patterns, the scale of SUSY breaking needs to be at least a few TeV. In some of these cases, the intermediate scale can be as low as ˜1012 GeV , for the SUSY scale to be ˜30 TeV . This has important consequences in the collider searches for SUSY particles and phenomenology of the lightest neutralino as dark matter.

SLAM, a Mathematica interface for SUSY spectrum generators

NASA Astrophysics Data System (ADS)

Marquard, Peter; Zerf, Nikolai

2014-03-01

We present and publish a Mathematica package, which can be used to automatically obtain any numerical MSSM input parameter from SUSY spectrum generators, which follow the SLHA standard, like SPheno, SOFTSUSY, SuSeFLAV or Suspect. The package enables a very comfortable way of numerical evaluations within the MSSM using Mathematica. It implements easy to use predefined high scale and low scale scenarios like mSUGRA or mhmax and if needed enables the user to directly specify the input required by the spectrum generators. In addition it supports an automatic saving and loading of SUSY spectra to and from a SQL data base, avoiding the rerun of a spectrum generator for a known spectrum. Catalogue identifier: AERX_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AERX_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 4387 No. of bytes in distributed program, including test data, etc.: 37748 Distribution format: tar.gz Programming language: Mathematica. Computer: Any computer where Mathematica version 6 or higher is running providing bash and sed. Operating system: Linux. Classification: 11.1. External routines: A SUSY spectrum generator such as SPheno, SOFTSUSY, SuSeFLAV or SUSPECT Nature of problem: Interfacing published spectrum generators for automated creation, saving and loading of SUSY particle spectra. Solution method: SLAM automatically writes/reads SLHA spectrum generator input/output and is able to save/load generated data in/from a data base. Restrictions: No general restrictions, specific restrictions are given in the manuscript. Running time: A single spectrum calculation takes much less than one second on a modern PC.

Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition.

PubMed

Mamantopoulos, Michail; Ronchi, Francesca; Van Hauwermeiren, Filip; Vieira-Silva, Sara; Yilmaz, Bahtiyar; Martens, Liesbet; Saeys, Yvan; Drexler, Stefan K; Yazdi, Amir S; Raes, Jeroen; Lamkanfi, Mohamed; McCoy, Kathy D; Wullaert, Andy

2017-08-15

The gut microbiota regulate susceptibility to multiple human diseases. The Nlrp6-ASC inflammasome is widely regarded as a hallmark host innate immune axis that shapes the gut microbiota composition. This notion stems from studies reporting dysbiosis in mice lacking these inflammasome components when compared with non-littermate wild-type animals. Here, we describe microbial analyses in inflammasome-deficient mice while minimizing non-genetic confounders using littermate-controlled Nlrp6-deficient mice and ex-germ-free littermate-controlled ASC-deficient mice that were all allowed to shape their gut microbiota naturally after birth. Careful microbial phylogenetic analyses of these cohorts failed to reveal regulation of the gut microbiota composition by the Nlrp6- and ASC-dependent inflammasomes. Our results obtained in two geographically separated animal facilities dismiss a generalizable impact of Nlrp6- and ASC-dependent inflammasomes on the composition of the commensal gut microbiota and highlight the necessity for littermate-controlled experimental design in assessing the influence of host immunity on gut microbial ecology. Copyright © 2017 Elsevier Inc. All rights reserved.

Towards a complete A4 × SU(5) SUSY GUT

NASA Astrophysics Data System (ADS)

Björkeroth, Fredrik; de Anda, Francisco J.; de Medeiros Varzielas, Ivo; King, Stephen F.

2015-06-01

We propose a renormalisable model based on A 4 family symmetry with an SU(5) grand unified theory (GUT) which leads to the minimal supersymmetric standard model (MSSM) with a ℤ9 × ℤ6 symmetry provides the fermion mass hierarchy in both the quark and lepton sectors, while ℤ {4/ R } symmetry is broken to ℤ {2/ R }, identified as usual R-parity. Proton decay is highly sup-pressed by these symmetries. The strong CP problem is solved in a similar way to the Nelson-Barr mechanism. We discuss both the A 4 and SU(5) symmetry breaking sectors, including doublet-triplet splitting, Higgs mixing and the origin of the μ term. The model provides an excellent fit (better than one sigma) to all quark and lepton (including neu-trino) masses and mixing with spontaneous CP violation. With the A 4 vacuum alignments, (0, 1, 1) and (1, 3, 1), the model predicts the entire PMNS mixing matrix with no free pa-rameters, up to a relative phase, selected to be 2π/3 from a choice of the nine complex roots of unity, which is identified as the leptogenesis phase. The model predicts a normal neutrino mass hierarchy with leptonic angles θ{13/ ι } ≈ 8.7∘, θ{12/ ι } ≈ 34∘, θ{23/ ι } ≈ 46∘ and an oscillation phase δ ι ≈ - 87∘.

Gut microbiome and innate immune response patterns in IgE-associated eczema.

PubMed

West, C E; Rydén, P; Lundin, D; Engstrand, L; Tulic, M K; Prescott, S L

2015-09-01

Gut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling. We examined gut microbiome development in the first year of life in relation to innate immune responses and onset of IgE-associated eczema over the first 2.5 years in predisposed children due to maternal atopy [www.anzctr.org.au, trial ID ACTRN12606000280505]. Microbial composition and diversity were analysed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1 week, 1 month and 12 months in infants (n = 10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5 years of age (n = 10). Microbiome data at 1 week and 1 month were analysed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6 months of age. The relative abundance of Gram-positive Ruminococcaceae was lower at 1 week of age in infants developing IgE-associated eczema, compared with controls (P = 0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL-6 (-0.567, P = 0.042) and TNF-α (-0.597, P = 0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4-induced TNF-α (rs = -0.629, P = 0.024). This relationship persisted at 1 month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Proteobacteria phylum) and TLR4-induced TNF-α (rs = -0.697, P = 0.038) and Enterobacteriaceae and IL-6 (rs = -0.709, P = 0.035). Mothers whose infants developed IgE-associated eczema had lower α-diversity of Bacteroidetes (P = 0.04) although this was not seen later in their infants. At 1 year, α-diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (P = 0.002). Our findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated

Coupled Boltzmann computation of mixed axion neutralino dark matter in the SUSY DFSZ axion model

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Lessa, Andre; Serce, Hasan

2014-10-01

The supersymmetrized DFSZ axion model is highly motivated not only because it offers solutions to both the gauge hierarchy and strong CP problems, but also because it provides a solution to the SUSY μ-problem which naturally allows for a Little Hierarchy. We compute the expected mixed axion-neutralino dark matter abundance for the SUSY DFSZ axion model in two benchmark cases—a natural SUSY model with a standard neutralino underabundance (SUA) and an mSUGRA/CMSSM model with a standard overabundance (SOA). Our computation implements coupled Boltzmann equations which track the radiation density along with neutralino, axion, axion CO (produced via coherent oscillations), saxion, saxion CO, axino and gravitino densities. In the SUSY DFSZ model, axions, axinos and saxions go through the process of freeze-in—in contrast to freeze-out or out-of-equilibrium production as in the SUSY KSVZ model—resulting in thermal yields which are largely independent of the re-heat temperature. We find the SUA case with suppressed saxion-axion couplings (ξ=0) only admits solutions for PQ breaking scale falesssim 6× 1012 GeV where the bulk of parameter space tends to be axion-dominated. For SUA with allowed saxion-axion couplings (ξ =1), then fa values up to ~ 1014 GeV are allowed. For the SOA case, almost all of SUSY DFSZ parameter space is disallowed by a combination of overproduction of dark matter, overproduction of dark radiation or violation of BBN constraints. An exception occurs at very large fa~ 1015-1016 GeV where large entropy dilution from CO-produced saxions leads to allowed models.

SUSI 62 A Robust and Safe Parachute Uav with Long Flight Time and Good Payload

NASA Astrophysics Data System (ADS)

Thamm, H. P.

2011-09-01

In many research areas in the geo-sciences (erosion, land use, land cover change, etc.) or applications (e.g. forest management, mining, land management etc.) there is a demand for remote sensing images of a very high spatial and temporal resolution. Due to the high costs of classic aerial photo campaigns, the use of a UAV is a promising option for obtaining the desired remote sensed information at the time it is needed. However, the UAV must be easy to operate, safe, robust and should have a high payload and long flight time. For that purpose, the parachute UAV SUSI 62 was developed. It consists of a steel frame with a powerful 62 cm3 2- stroke engine and a parachute wing. The frame can be easily disassembled for transportation or to replace parts. On the frame there is a gimbal mounted sensor carrier where different sensors, standard SLR cameras and/or multi-spectral and thermal sensors can be mounted. Due to the design of the parachute, the SUSI 62 is very easy to control. Two different parachute sizes are available for different wind speed conditions. The SUSI 62 has a payload of up to 8 kg providing options to use different sensors at the same time or to extend flight duration. The SUSI 62 needs a runway of between 10 m and 50 m, depending on the wind conditions. The maximum flight speed is approximately 50 km/h. It can be operated in a wind speed of up to 6 m/s. The design of the system utilising a parachute UAV makes it comparatively safe as a failure of the electronics or the remote control only results in the UAV coming to the ground at a slow speed. The video signal from the camera, the GPS coordinates and other flight parameters are transmitted to the ground station in real time. An autopilot is available, which guarantees that the area of investigation is covered at the desired resolution and overlap. The robustly designed SUSI 62 has been used successfully in Europe, Africa and Australia for scientific projects and also for agricultural, forestry and

The Potential Link between Gut Microbiota and IgE-Mediated Food Allergy in Early Life

PubMed Central

Molloy, John; Allen, Katrina; Collier, Fiona; Tang, Mimi L. K.; Ward, Alister C.; Vuillermin, Peter

2013-01-01

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field. PMID:24351744

GUT Model Hierarchies from Intersecting Branes

NASA Astrophysics Data System (ADS)

Kokorelis, Christos

2002-08-01

By employing D6-branes intersecting at angles in D = 4 type I strings, we construct the first examples of three generation string GUT models (PS-A class), that contain at low energy exactly the standard model spectrum with no extra matter and/or extra gauge group factors. They are based on the group SU(4)C × SU(2)L × SU(2)R. The models are non-supersymmetric, even though SUSY is unbroken in the bulk. Baryon number is gauged and its anomalies are cancelled through a generalized Green-Schwarz mechanism. We also discuss models (PS-B class) which at low energy have the standard model augmented by an anomaly free U(1) symmetry and show that multibrane wrappings correspond to a trivial redefinition of the surviving global U(1) at low energies. There are no colour triplet couplings to mediate proton decay and proton is stable. The models are compatible with a low string scale of energy less that 650 GeV and are directly testable at present or future accelerators as they predict the existence of light left handed weak fermion doublets at energies between 90 and 246 GeV. The neutrinos get a mass through an unconventional see-saw mechanism. The mass relation me = md at the GUT scale is recovered. Imposing supersymmetry at particular intersections generates non-zero Majorana masses for right handed neutrinos as well providing the necessary singlets needed to break the surviving anomaly free U(1), thus suggesting a gauge symmetry breaking method that can be applied in general left-right symmetric models.

Prospects for Higgs coupling measurements in SUSY with radiatively-driven naturalness

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Nagata, Natsumi; Serce, Hasan

2015-08-01

In the post-LHC8 world—where a Standard Model-like Higgs boson has been established but there is no sign of supersymmetry (SUSY)—the detailed profiling of the Higgs boson properties has emerged as an important road towards discovery of new physics. We present calculations of the expected deviations in Higgs boson couplings κτ ,b, κt, κW ,Z, κg and κγ versus the naturalness measure ΔEW . Low values of ΔEW˜10 - 30 give rise to a natural little hierarchy characterized by light Higgsinos with a mass of μ ˜mZ while top squarks are highly mixed but lie in the several TeV range. For such models with radiatively driven naturalness, one expects the Higgs boson h to look very SM-like although deviations can occur. The more promising road to SUSY discovery requires direct Higgsino pair production at a high energy e+e- collider operating with the center-of-mass energy √{s }>2 μ ˜√{2 ΔEW }mZ.

An inclusive SUSY approach to position dependent mass systems

NASA Astrophysics Data System (ADS)

Karthiga, S.; Chithiika Ruby, V.; Senthilvelan, M.

2018-06-01

The supersymmetry (SUSY) formalism for a position dependent mass problem with a more general ordering is yet to be formulated. In this paper, we present an unified SUSY approach for PDM problems of any ordering. Highlighting all non-Hermitian Hamiltonians of PDM problems are of quasi-Hermitian nature, the SUSY operators of these problems are constructed using similarity transformation. The methodology that we propose here is applicable for even more general cases where the kinetic energy term is represented by linear combination of infinite number of possible orderings. We illustrate the method with an example, namely Mathews-Lakshmanan (ML) oscillator. Our results show that the latter system is shape invariant for all possible orderings. We derive eigenvalues and eigenvectors of this nonlinear oscillator for all possible orderings including Hermitian and non-Hermitian ones.

Using experimental data to test and improve SUSY theories

NASA Astrophysics Data System (ADS)

Wang, Ting

There are several pieces of evidence that our world is described by a supersymmetric extension of the Standard Model. In this thesis, I assume this is the case and study how to use experimental data to test and improve supersymmetric standard models. Several experimental signatures and their implications are covered in this thesis: the result of the branching ratio of b → sgamma is used to put constraints on SUSY models; the measured time-dependent CP asymmetry in the B → φKS process is used to test unification scale models; the excess of positrons from cosmic rays helps us to test the property of the Lightest Supersymmetric Particle and the Cold Dark Matter production mechanisms; the LEP higgs search results are used to classify SUSY models; SUSY signatures at the Tevatron are used to distinguish different unification scale models; by considering the mu problem, SUSY theories are improved. Due to the large unknown parameter space, all of the above inputs should be used to partially reconstruct the soft Lagrangian, which is the central part of the model. Combining the results from these analysis, a significant amount of knowledge about the underlying theory has been learned. In the next several years, there will be more data coming. The methods and results in this thesis will be useful for dealing with future data.

Cornering natural SUSY at LHC Run II and beyond

NASA Astrophysics Data System (ADS)

Buckley, Matthew R.; Feld, David; Macaluso, Sebastian; Monteux, Angelo; Shih, David

2017-08-01

We derive the latest constraints on various simplified models of natural SUSY with light higgsinos, stops and gluinos, using a detailed and comprehensive reinterpretation of the most recent 13 TeV ATLAS and CMS searches with ˜ 15 fb-1 of data. We discuss the implications of these constraints for fine-tuning of the electroweak scale. While the most "vanilla" version of SUSY (the MSSM with R-parity and flavor-degenerate sfermions) with 10% fine-tuning is ruled out by the current constraints, models with decoupled valence squarks or reduced missing energy can still be fully natural. However, in all of these models, the mediation scale must be extremely low ( <100 TeV). We conclude by considering the prospects for the high-luminosity LHC era, where we expect the current limits on particle masses to improve by up to ˜ 1 TeV, and discuss further model-building directions for natural SUSY that are motivated by this work.

Cornering natural SUSY at LHC Run II and beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buckley, Matthew R.; Feld, David; Macaluso, Sebastian

We derive the latest constraints on various simplified models of natural SUSY with light higgsinos, stops and gluinos, using a detailed and comprehensive reinterpretation of the most recent 13 TeV ATLAS and CMS searches with ~ 15 fb -1 of data. We discuss the implications of these constraints for fine-tuning of the electroweak scale. While the most “vanilla” version of SUSY (the MSSM with R-parity and flavor-degenerate sfermions) with 10% fine-tuning is ruled out by the current constraints, models with decoupled valence squarks or reduced missing energy can still be fully natural. However, in all of these models, the mediationmore » scale must be extremely low (<100 TeV). We conclude by considering the prospects for the high-luminosity LHC era, where we expect the current limits on particle masses to improve by up to ~ 1 TeV, and discuss further model-building directions for natural SUSY that are motivated by this work.« less

Cornering natural SUSY at LHC Run II and beyond

DOE PAGES

Buckley, Matthew R.; Feld, David; Macaluso, Sebastian; ...

2017-08-25

We derive the latest constraints on various simplified models of natural SUSY with light higgsinos, stops and gluinos, using a detailed and comprehensive reinterpretation of the most recent 13 TeV ATLAS and CMS searches with ~ 15 fb -1 of data. We discuss the implications of these constraints for fine-tuning of the electroweak scale. While the most “vanilla” version of SUSY (the MSSM with R-parity and flavor-degenerate sfermions) with 10% fine-tuning is ruled out by the current constraints, models with decoupled valence squarks or reduced missing energy can still be fully natural. However, in all of these models, the mediationmore » scale must be extremely low (<100 TeV). We conclude by considering the prospects for the high-luminosity LHC era, where we expect the current limits on particle masses to improve by up to ~ 1 TeV, and discuss further model-building directions for natural SUSY that are motivated by this work.« less

Dark matter as ultralight axion-like particle in E6 × U(1)X GUT with QCD axion

NASA Astrophysics Data System (ADS)

Corianò, Claudio; Frampton, Paul H.

2018-07-01

Axion-like fields are naturally generated by a mechanism of anomaly cancellation of one or more anomalous gauge abelian symmetries at the Planck scale, emerging as duals of a two-form from the massless bosonic sector of string theory. This suggests an analogy of the Green-Schwarz mechanism of anomaly cancellation, at field theory level, which results in one or more Stueckelberg pseudoscalars. In the case of a single Stueckelberg pseudoscalar b, vacuum misalignments at phase transitions in the early Universe at the GUT scale provide a small mass - due to instanton suppression of the periodic potential - for a component of b, denoted as χ and termed the "axi-Higgs", which is a physical axion-like particle. The coupling of the axi-Higgs to the gauge sector via Wess-Zumino terms is suppressed by the Planck mass, which guarantees its decoupling, while its angle of misalignment is related to MGUT. We build a gauged E6 × U (1) model with anomalous U (1). It contains both an automatic invisible QCD axion and an ultra-light axi-Higgs. The invisible axion present in the model solves the strong CP problem and has mass in the conventional range while the axi-Higgs, which can act as dark matter, is sufficiently light (10-22 eV eV) to solve short-distance problems which confront other cold dark matter candidates.

Little SUSY hierarchy in mixed modulus-anomaly mediation

NASA Astrophysics Data System (ADS)

Choi, Kiwoon; Jeong, Kwang Sik; Kobayashi, Tatsuo; Okumura, Ken-ichi

2006-02-01

Motivated by the KKLT string compactification involving a supersymmetry-breaking uplifting potential, we examine 4D effective supergravity with a generic form of uplifting potential, focusing on the possibility that the resulting mixed modulus-anomaly mediated soft terms realize the little hierarchy between the Higgs boson masses mH and the sparticle masses mSUSY. It is noted that for some type of uplifting potential, the anomaly-mediated contribution to mH2 at MGUT can cancel the subsequent renormalization group evolution of mH2 down to TeV scale, thereby the model can naturally realize the little hierarchy mH2 ∼mSUSY2 / 8π2 which is desirable for the lightest Higgs boson mass to satisfy the experimental bound. In such models, the other Higgs mass parameters μ and B can have the desirable size μ ∼ B ∼mH without severe fine-tuning of parameters, although the gravitino is much heavier than the Higgs boson. Those models for the little hierarchy avoid naturally the dangerous SUSY flavor and CP violations, and predict nearly degenerate low energy gaugino masses, pure Higgsino LSP, and also a specific relation between the stop and gaugino masses.

The point of E 8 in F-theory GUTs

NASA Astrophysics Data System (ADS)

Heckman, Jonathan J.; Tavanfar, Alireza; Vafa, Cumrun

2010-08-01

We show that in F-theory GUTs, a natural explanation of flavor hierarchies in the quark and lepton sector requires a single point of E 8 enhancement in the internal geometry, from which all Yukawa couplings originate. The monodromy group acting on the seven-brane configuration plays a key role in this analysis. Moreover, the E 8 structure automatically leads to the existence of the additional fields and interactions needed for minimal gauge mediated supersymmetry breaking, and almost nothing else. Surprisingly, we find that in all but one Dirac neutrino scenario the messenger fields in the gauge mediated supersymmetry breaking sector transform as vector-like pairs in the 10 oplus overline {10} of SU(5). We also classify dark matter candidates available from this enhancement point, and rule out both annihilating and decaying dark matter scenarios as explanations for the recent experiments PAMELA, ATIC and FERMI. In F-theory GUT models, a 10-100 MeV mass gravitino remains as the prime candidate for dark matter, thus suggesting an astrophysical origin for recent experimental signals.

Prospects for axion detection in natural SUSY with mixed axion-higgsino dark matter: back to invisible?

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Serce, Hasan

2017-06-01

Under the expectation that nature is natural, we extend the Standard Model to include SUSY to stabilize the electroweak sector and PQ symmetry to stabilize the QCD sector. Then natural SUSY arises from a Kim-Nilles solution to the SUSY μ problem which allows for a little hierarchy where μ~ fa2/MP~ 100-300 GeV while the SUSY particle mass scale mSUSY~ 1-10 TeV gg μ. Dark matter then consists of two particles: a higgsino-like WIMP and a SUSY DFSZ axion. The range of allowed axion mass values ma depends on the mixed axion-higgsino relic density. The range of ma is actually restricted in this case by limits on WIMPs from direct and indirect detection experiments. We plot the expected axion detection rate at microwave cavity experiments. The axion-photon-photon coupling is severely diminished by charged higgsino contributions to the anomalous coupling. In this case, the axion may retreat, at least temporarily, back into the regime of near invisibility. From our results, we urge new ideas for techniques which probe both deeper and more broadly into axion coupling versus axion mass parameter space.

Holographic entanglement entropy and entanglement thermodynamics of 'black' non-susy D3 brane

NASA Astrophysics Data System (ADS)

Bhattacharya, Aranya; Roy, Shibaji

2018-06-01

Like BPS D3 brane, the non-supersymmetric (non-susy) D3 brane of type IIB string theory is also known to have a decoupling limit and leads to a non-supersymmetric AdS/CFT correspondence. The throat geometry in this case represents a QFT which is neither conformal nor supersymmetric. The 'black' version of the non-susy D3 brane in the decoupling limit describes a QFT at finite temperature. Here we first compute the entanglement entropy for small subsystem of such QFT from the decoupled geometry of 'black' non-susy D3 brane using holographic technique. Then we study the entanglement thermodynamics for the weakly excited states of this QFT from the asymptotically AdS geometry of the decoupled 'black' non-susy D3 brane. We observe that for small subsystem this background indeed satisfies a first law like relation with a universal (entanglement) temperature inversely proportional to the size of the subsystem and an (entanglement) pressure normal to the entangling surface. Finally we show how the entanglement entropy makes a cross-over to the thermal entropy at high temperature.

Physics of the gut: How polymers dynamically structure the gut environment

NASA Astrophysics Data System (ADS)

Preska Steinberg, Asher; Datta, Sujit; Bogatyrev, Said; Ismagilov, Rustem

While the gut microbiome and biological regulation of the gut environment is being exhaustively studied by the microbiology community, little is known about the rich physics that governs the macro- and microstructure of the gut environment. The mammalian gut abounds in soft materials; ranging from soluble polymers (e.g. dietary fibers, therapeutic polymers and mucins) to colloidal matter (e.g. bacteria, viruses and nanoparticles carrying drugs). We have found experimentally that soluble polymers can dynamically re-structure the colonic mucus hydrogel by modulating its degree of swelling. We implemented a mean-field Flory-Huggins model to reveal that these polymer-mucus interactions can be captured using a simple, first principles thermodynamics model. In this model, the amount of deswelling increases with polymer concentration and size. We then used these physical principles to make predictions about how different polymer solutions affect the structure of mucus. Lastly, we explore applying this framework and similar physical principles to a variety of biological problems in the gut.

General structure of democratic mass matrix of quark sector in E6 model

NASA Astrophysics Data System (ADS)

Ciftci, R.; ćiftci, A. K.

2016-03-01

An extension of the Standard Model (SM) fermion sector, which is inspired by the E6 Grand Unified Theory (GUT) model, might be a good candidate to explain a number of unanswered questions in SM. Existence of the isosinglet quarks might explain great mass difference of bottom and top quarks. Also, democracy on mass matrix elements is a natural approach in SM. In this study, we have given general structure of Democratic Mass Matrix (DMM) of quark sector in E6 model.

The BSM-AI project: SUSY-AI-generalizing LHC limits on supersymmetry with machine learning

NASA Astrophysics Data System (ADS)

Caron, Sascha; Kim, Jong Soo; Rolbiecki, Krzysztof; de Austri, Roberto Ruiz; Stienen, Bob

2017-04-01

A key research question at the Large Hadron Collider is the test of models of new physics. Testing if a particular parameter set of such a model is excluded by LHC data is a challenge: it requires time consuming generation of scattering events, simulation of the detector response, event reconstruction, cross section calculations and analysis code to test against several hundred signal regions defined by the ATLAS and CMS experiments. In the BSM-AI project we approach this challenge with a new idea. A machine learning tool is devised to predict within a fraction of a millisecond if a model is excluded or not directly from the model parameters. A first example is SUSY-AI, trained on the phenomenological supersymmetric standard model (pMSSM). About 300, 000 pMSSM model sets - each tested against 200 signal regions by ATLAS - have been used to train and validate SUSY-AI. The code is currently able to reproduce the ATLAS exclusion regions in 19 dimensions with an accuracy of at least 93%. It has been validated further within the constrained MSSM and the minimal natural supersymmetric model, again showing high accuracy. SUSY-AI and its future BSM derivatives will help to solve the problem of recasting LHC results for any model of new physics. SUSY-AI can be downloaded from http://susyai.hepforge.org/. An on-line interface to the program for quick testing purposes can be found at http://www.susy-ai.org/.

Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist

PubMed Central

Spaulding, Caitlin N.; Klein, Roger D.; Ruer, Ségolène; Kau, Andrew L.; Schreiber, Henry L.; Cusumano, Zachary T.; Dodson, Karen W.; Pinkner, Jerome S.; Fremont, Daved H.; Janetka, James W.; Remaut, Han; Gordon, Jeffrey I.; Hultgren, Scott J.

2017-01-01

Summary Urinary tract infections (UTI) caused by uropathogenic E. coli (UPEC) affect 150 million people annually1,2. Despite effective antibiotic therapy, 30–50% of patients experience recurrent UTI (rUTI)1. Additionally, the growing prevelance of UPEC resistant to last-line antibiotic treatments, and more recently carbapenems and colistin, make UTIs a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections3–5. UPEC strains establish reservoirs in the gut from which they are shed in the feces, can colonize the peri-urethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTI6. UPEC isolates encode up to 16 distinct chaperone-usher pathway (CUP) pili and each pilus type likely enables colonization of a habitat in the host or environment7. For example, the type 1 pilus adhesin, FimH, binds mannose on the bladder surface, mediating bladder colonization. However, little is known regarding the mechanisms underlying UPEC persistence in the gut5. Using a mouse model, we found that F17-like and type 1 pili promote intestinal colonization and show distinct binding to epithelial cells distributed along colonic crypts. Phylogenomic and structural analyses reveal that F17-like pili are closely related to pilus types carried by intestinal pathogens, but are restricted to extra-intestinal pathogenic E. coli. Moreover, we show that targeting FimH with a high-affinity inhibitor, mannoside M4284, reduces intestinal colonization of genetically diverse UPEC isolates, while simultaneously treating UTI, without significantly disrupting the the structural configuration of the gut microbiota. By selectively depleting the intestinal UPEC reservoir, mannosides could significantly reduce the rate of UTI and rUTI. PMID:28614296

6-Mercaptopurine reduces macrophage activation and gut epithelium proliferation through inhibition of GTPase Rac1.

PubMed

Marinković, Goran; Hamers, Anouk A J; de Vries, Carlie J M; de Waard, Vivian

2014-09-01

Inflammatory bowel disease is characterized by chronic intestinal inflammation. Azathioprine and its metabolite 6-mercaptopurine (6-MP) are effective immunosuppressive drugs that are widely used in patients with inflammatory bowel disease. However, established understanding of their immunosuppressive mechanism is limited. Azathioprine and 6-MP have been shown to affect small GTPase Rac1 in T cells and endothelial cells, whereas the effect on macrophages and gut epithelial cells is unknown. Macrophages (RAW cells) and gut epithelial cells (Caco-2 cells) were activated by cytokines and the effect on Rac1 signaling was assessed in the presence or absence of 6-MP. Rac1 is activated in macrophages and epithelial cells, and treatment with 6-MP resulted in Rac1 inhibition. In macrophages, interferon-γ induced downstream signaling through c-Jun-N-terminal Kinase (JNK) resulting in inducible nitric oxide synthase (iNOS) expression. iNOS expression was reduced by 6-MP in a Rac1-dependent manner. In epithelial cells, 6-MP efficiently inhibited tumor necrosis factor-α-induced expression of the chemokines CCL2 and interleukin-8, although only interleukin-8 expression was inhibited in a Rac1-dependent manner. In addition, activation of the transcription factor STAT3 was suppressed in a Rac1-dependent fashion by 6-MP, resulting in reduced proliferation of the epithelial cells due to diminished cyclin D1 expression. These data demonstrate that 6-MP affects macrophages and gut epithelial cells beneficially, in addition to T cells and endothelial cells. Furthermore, mechanistic insight is provided to support development of Rac1-specific inhibitors for clinical use in inflammatory bowel disease.

Early-life gut microbiome composition and milk allergy resolution

PubMed Central

Bunyavanich, Supinda; Shen, Nan; Grishin, Alexander; Wood, Robert; Burks, Wesley; Dawson, Peter; Jones, Stacie M.; Leung, Donald; Sampson, Hugh; Sicherer, Scott; Clemente, Jose C.

2016-01-01

Background Gut microbiota may play a role in the natural history of cow’s milk allergy Objective To examine the association between early life gut microbiota and the resolution of cow’s milk allergy Methods We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy (CoFAR) observational study of food allergy. Fecal samples were collected at age 3–16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using QIIME (Quantitative Insights into Microbial Ecology), PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), and STAMP (Statistical Analysis of Metagenomic Profiles). Results Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3–6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = 0.047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η2 = 0.43, ANOVA P = 0.034). Conclusions Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy. PMID:27292825

General structure of democratic mass matrix of quark sector in E{sub 6} model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ciftci, R., E-mail: rciftci@cern.ch; Çiftci, A. K., E-mail: abbas.kenan.ciftci@cern.ch

2016-03-25

An extension of the Standard Model (SM) fermion sector, which is inspired by the E{sub 6} Grand Unified Theory (GUT) model, might be a good candidate to explain a number of unanswered questions in SM. Existence of the isosinglet quarks might explain great mass difference of bottom and top quarks. Also, democracy on mass matrix elements is a natural approach in SM. In this study, we have given general structure of Democratic Mass Matrix (DMM) of quark sector in E6 model.

High-frequency spectral ultrasound imaging (SUSI) visualizes early post-traumatic heterotopic ossification (HO) in a mouse model.

PubMed

Ranganathan, Kavitha; Hong, Xiaowei; Cholok, David; Habbouche, Joe; Priest, Caitlin; Breuler, Christopher; Chung, Michael; Li, John; Kaura, Arminder; Hsieh, Hsiao Hsin Sung; Butts, Jonathan; Ucer, Serra; Schwartz, Ean; Buchman, Steven R; Stegemann, Jan P; Deng, Cheri X; Levi, Benjamin

2018-04-01

Early treatment of heterotopic ossification (HO) is currently limited by delayed diagnosis due to limited visualization at early time points. In this study, we validate the use of spectral ultrasound imaging (SUSI) in an animal model to detect HO as early as one week after burn tenotomy. Concurrent SUSI, micro CT, and histology at 1, 2, 4, and 9weeks post-injury were used to follow the progression of HO after an Achilles tenotomy and 30% total body surface area burn (n=3-5 limbs per time point). To compare the use of SUSI in different types of injury models, mice (n=5 per group) underwent either burn/tenotomy or skin incision injury and were imaged using a 55MHz probe on VisualSonics VEVO 770 system at one week post injury to evaluate the ability of SUSI to distinguish between edema and HO. Average acoustic concentration (AAC) and average scatterer diameter (ASD) were calculated for each ultrasound image frame. Micro CT was used to calculate the total volume of HO. Histology was used to confirm bone formation. Using SUSI, HO was visualized as early as 1week after injury. HO was visualized earliest by 4weeks after injury by micro CT. The average acoustic concentration of HO was 33% more than that of the control limb (n=5). Spectroscopic foci of HO present at 1week that persisted throughout all time points correlated with the HO present at 9weeks on micro CT imaging. SUSI visualizes HO as early as one week after injury in an animal model. SUSI represents a new imaging modality with promise for early diagnosis of HO. Copyright © 2018 Elsevier Inc. All rights reserved.

Higgs mass corrections in the SUSY B - L model with inverse seesaw

NASA Astrophysics Data System (ADS)

Elsayed, A.; Khalil, S.; Moretti, S.

2012-08-01

In the context of the Supersymmetric (SUSY) B - L (Baryon minus Lepton number) model with inverse seesaw mechanism, we calculate the one-loop radiative corrections due to right-handed (s)neutrinos to the mass of the lightest Higgs boson when the latter is Standard Model (SM)-like. We show that such effects can be as large as O (100) GeV, thereby giving an absolute upper limit on such a mass around 180 GeV. The importance of this result from a phenomenological point of view is twofold. On the one hand, this enhancement greatly reconciles theory and experiment, by alleviating the so-called 'little hierarchy problem' of the minimal SUSY realization, whereby the current experimental limit on the SM-like Higgs mass is very near its absolute upper limit predicted theoretically, of 130 GeV. On the other hand, a SM-like Higgs boson with mass below 180 GeV is still well within the reach of the Large Hadron Collider (LHC), so that the SUSY realization discussed here is just as testable as the minimal version.

Gravity waves and the LHC: towards high-scale inflation with low-energy SUSY

NASA Astrophysics Data System (ADS)

He, Temple; Kachru, Shamit; Westphal, Alexander

2010-06-01

It has been argued that rather generic features of string-inspired inflationary theories with low-energy supersymmetry (SUSY) make it difficult to achieve inflation with a Hubble scale H > m 3/2, where m 3/2 is the gravitino mass in the SUSY-breaking vacuum state. We present a class of string-inspired supergravity realizations of chaotic inflation where a simple, dynamical mechanism yields hierarchically small scales of post-inflationary supersymmetry breaking. Within these toy models we can easily achieve small ratios between m 3/2 and the Hubble scale of inflation. This is possible because the expectation value of the superpotential < W> relaxes from large to small values during the course of inflation. However, our toy models do not provide a reasonable fit to cosmological data if one sets the SUSY-breaking scale to m 3/2 ≤ TeV. Our work is a small step towards relieving the apparent tension between high-scale inflation and low-scale supersymmetry breaking in string compactifications.

Early-life gut microbiome composition and milk allergy resolution.

PubMed

Bunyavanich, Supinda; Shen, Nan; Grishin, Alexander; Wood, Robert; Burks, Wesley; Dawson, Peter; Jones, Stacie M; Leung, Donald Y M; Sampson, Hugh; Sicherer, Scott; Clemente, Jose C

2016-10-01

Gut microbiota may play a role in the natural history of cow's milk allergy. We sought to examine the association between early-life gut microbiota and the resolution of cow's milk allergy. We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η 2  = 0.43; ANOVA P = .034). Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Multiverse dark matter: SUSY or axions

NASA Astrophysics Data System (ADS)

D'Eramo, Francesco; Hall, Lawrence J.; Pappadopulo, Duccio

2014-11-01

The observed values of the cosmological constant and the abundance of Dark Matter (DM) can be successfully understood, using certain measures, by imposing the anthropic requirement that density perturbations go non-linear and virialize to form halos. This requires a probability distribution favoring low amounts of DM, i.e. low values of the PQ scale f for the QCD axion and low values of the superpartner mass scale for LSP thermal relics. In theories with independent scanning of multiple DM components, there is a high probability for DM to be dominated by a single component. For example, with independent scanning of f and , TeV-scale LSP DM and an axion solution to the strong CP problem are unlikely to coexist. With thermal LSP DM, the scheme allows an understanding of a Little SUSY Hierarchy with multi-TeV superpartners. Alternatively, with axion DM, PQ breaking before (after) inflation leads to f typically below (below) the projected range of the current ADMX experiment of f = (3 - 30) × 1011 GeV, providing strong motivation to develop experimental techniques for probing lower f.

Probiotics, gut microbiota and health.

PubMed

Butel, M-J

2014-01-01

The human gut is a huge complex ecosystem where microbiota, nutrients, and host cells interact extensively, a process crucial for the gut homeostasis and host development with a real partnership. The various bacterial communities that make up the gut microbiota have many functions including metabolic, barrier effect, and trophic functions. Hence, any dysbiosis could have negative consequences in terms of health and many diseases have been associated to impairment of the gut microbiota. These close relationships between gut microbiota, health, and disease, have led to great interest in using probiotics (i.e. live micro-organisms), or prebiotics (i.e. non-digestible substrates) to positively modulate the gut microbiota to prevent or treat some diseases. This review focuses on probiotics, their mechanisms of action, safety, and major health benefits. Health benefits remain to be proven in some indications, and further studies on the best strain(s), dose, and algorithm of administration to be used are needed. Nevertheless, probiotic administration seems to have a great potential in terms of health that justifies more research. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Comparative Gut Microbiota of 59 Neotropical Bird Species

PubMed Central

Hird, Sarah M.; Sánchez, César; Carstens, Bryan C.; Brumfield, Robb T.

2015-01-01

The gut microbiota of vertebrates are essential to host health. Most non-model vertebrates, however, lack even a basic description of natural gut microbiota biodiversity. Here, we sampled 116 intestines from 59 Neotropical bird species and used the V6 region of the 16S rRNA molecule as a microbial fingerprint (average coverage per bird ~80,000 reads). A core microbiota of Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria was identified, as well as several gut-associated genera. We tested 18 categorical variables associated with each bird for significant correlation to the gut microbiota; host taxonomic categories were most frequently significant and explained the most variation. Ecological variables (e.g., diet, foraging stratum) were also frequently significant but explained less variation. Little evidence was found for a significant influence of geographic space. Finally, we suggest that microbial sampling during field collection of organisms would propel biological understanding of evolutionary history and ecological significance of host-associated microbiota. PMID:26733954

Mixed axion/neutralino dark matter in the SUSY DFSZ axion model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Kyu Jung; Baer, Howard; Chun, Eung Jin, E-mail: bae@nhn.ou.edu, E-mail: baer@nhn.ou.edu, E-mail: ejchun@kias.re.kr

2013-12-01

We examine mixed axion/neutralino cold dark matter production in the SUSY DFSZ axion model where an axion superfield couples to Higgs superfields. We calculate a wide array of axino and saxion decay modes along with their decay temperatures, and thermal and non-thermal production rates. For a SUSY benchmark model with a standard underabundance (SUA) of Higgsino-like dark matter (DM), we find for the PQ scale f{sub a}∼<10{sup 12} GeV that the DM abundance is mainly comprised of axions as the saxion/axino decay occurs before the standard neutralino freeze-out and thus its abundance remains suppressed. For 10{sup 12}∼10{sup 14} GeV, bothmore » neutralino dark matter and dark radiation are typically overproduced. For judicious parameter choices, these can be suppressed and the combined neutralino/axion abundance brought into accord with measured values. A SUSY benchmark model with a standard overabundance (SOA) of bino DM is also examined and typically remains excluded due at least to too great a neutralino DM abundance for f{sub a}∼<10{sup 15} GeV. For f{sub a}∼>10{sup 15} GeV and lower saxion masses, large entropy production from saxion decay can dilute all relics and the SOA model can be allowed by all constraints.« less

CoMiniGut-a small volume in vitro colon model for the screening of gut microbial fermentation processes.

PubMed

Wiese, Maria; Khakimov, Bekzod; Nielsen, Sebastian; Sørensen, Helena; van den Berg, Frans; Nielsen, Dennis Sandris

2018-01-01

Driven by the growing recognition of the influence of the gut microbiota (GM) on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v). We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs) were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative abundance of

Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.

PubMed

Geurts, L; Neyrinck, A M; Delzenne, N M; Knauf, C; Cani, P D

2014-03-01

Crosstalk between organs is crucial for controlling numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Several pathological conditions, such as obesity and type 2 diabetes, are characterised by a loss of or excessive inter-organ communication that contributes to the development of disease. Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis). Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance. Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia. Recently, we hypothesised that specific metabolic dysregulations occurring at the level of numerous organs (e.g. gut, adipose tissue, muscles, liver and brain) rely from gut microbiota modifications. In this review, we discuss the mechanisms linking gut permeability, adipose tissue metabolism, and glucose homeostasis, and recent findings that show interactions between the gut microbiota, the endocannabinoid system and the apelinergic system. These specific systems are discussed in the context of the gut-to-peripheral organ axis (intestine, adipose tissue and brain) and impacts on metabolic regulation. In the present review, we also briefly describe the impact of a variety of non-digestible nutrients (i.e. inulin-type fructans, arabinoxylans, chitin glucans and polyphenols). Their effects on the composition of the gut microbiota and

Gut microbiota and liver diseases

PubMed Central

Minemura, Masami; Shimizu, Yukihiro

2015-01-01

Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

Clostridium perfringens Type E Virulence Traits Involved in Gut Colonization

PubMed Central

Redondo, Leandro M.; Carrasco, Juan M. Díaz; Redondo, Enzo A.; Delgado, Fernando; Miyakawa, Mariano E. Fernández

2015-01-01

Clostridium perfringens type E disease in ruminants has been characterized by hemorrhagic enteritis or sudden death. Although type E isolates are defined by the production of alpha and iota toxin, little is known about the pathogenesis of C. perfringens type E infections. Thus far, the role of iota toxin as a virulence factor is unknown. In this report, iota toxin showed positive effects on adherence and colonization of C. perfringens type E while having negative effect on the adherence of type A cells. In-vitro and in-vivo models suggest that toxinotype E would be particularly adapted to exploit the changes induced by iota toxin in the surface of epithelial cells. In addition, type E strains produce metabolites that affected the growth of potential intra-specific competitors. These results suggest that the alteration of the enterocyte morphology induced by iota toxin concomitantly with the specific increase of type E cell adhesion and the strong intra-specific growth inhibition of other strains could be competitive traits inherent to type E isolates that improve its fitness within the bovine gut environment. PMID:25799452

Simultaneous gut colonisation and infection by ESBL-producing Escherichia coli in hospitalised patients.

PubMed

Asir, Johny; Nair, Shashikala; Devi, Sheela; Prashanth, Kenchappa; Saranathan, Rajagopalan; Kanungo, Reba

2015-01-01

Extended spectrum betalactamase (ESBL)-producing organisms are a major cause of hospital-acquired infections. ESBL-producing Escherichia coli (E. coli) have been recovered from the hospital environment. These drug-resistant organisms have also been found to be present in humans as commensals. The present investigation intended to isolate ESBL-producing E. coli from the gut of already infected patients; to date, only a few studies have shown evidence of the gut microflora as a major source of infection. This study aimed to detect the presence of ESBL genes in E.coli that are isolated from the gut of patients who have already been infected with the same organism. A total of 70 non-repetitive faecal samples were collected from in-patients of our hospital. These in-patients were clinically diagnosed and were culture-positive for ESBL-producing E. coli either from blood, urine, or pus. Standard microbiological methods were used to detect ESBL from clinical and gut isolates. Genes coding for major betalactamase enzymes such as bla CTX-M , bla TEM, and bla SHV were investigated by polymerase chain reaction (PCR). ESBL-producing E. coli was isolated from 15 (21 per cent) faecal samples of the 70 samples that were cultured. PCR revealed that out of these 15 isolates, the bla CTX-M gene was found in 13 (86.6 per cent) isolates, the bla TEM was present in 11 (73.3 per cent) isolates, and bla SHV only in eight (53.3 per cent) isolates. All 15 clinical and gut isolates had similar phenotypic characters and eight of the 15 patients had similar pattern of genes (bla TEM, bla CTX-M, and bla SHV) in their clinical and gut isolates. Strains with multiple betalactamase genes that colonise the gut of hospitalised patients are a potential threat and it may be a potential source of infection.

Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

PubMed Central

Mikkelsen, Kristian H.; Frost, Morten; Bahl, Martin I.; Licht, Tine R.; Jensen, Ulrich S.; Rosenberg, Jacob; Pedersen, Oluf; Hansen, Torben; Rehfeld, Jens F.; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.

2015-01-01

Objective The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Methods Meal tests with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Results Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. Conclusion As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. Trial Registration clinicaltrials.gov NCT01633762 PMID:26562532

FAST TRACK COMMUNICATION: SUSY transformations with complex factorization constants: application to spectral singularities

NASA Astrophysics Data System (ADS)

Samsonov, Boris F.

2010-10-01

Supersymmetric (SUSY) transformation operators with complex factorization constants are analyzed as operators acting in the Hilbert space of functions square integrable on the positive semiaxis. The obtained results are applied to Hamiltonians possessing spectral singularities which are non-Hermitian SUSY partners of self-adjoint operators. A new regularization procedure for the resolution of the identity operator in terms of a continuous biorthonormal set of the non-Hermitian Hamiltonian eigenfunctions is proposed. It is also argued that if the binorm of continuous spectrum eigenfunctions is interpreted in the same way as the norm of similar functions in the usual Hermitian case, then one can state that the function corresponding to a spectral singularity has zero binorm.

A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0653 TITLE: A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS...Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...compare the gut microbiome of subjects with RMS and PPMS. Major Task 1: To seek and obtain HRPO approval Major Task 2: Identification and

The hyperbolic step potential: Anti-bound states, SUSY partners and Wigner time delays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gadella, M.; Kuru, Ş.; Negro, J., E-mail: jnegro@fta.uva.es

We study the scattering produced by a one dimensional hyperbolic step potential, which is exactly solvable and shows an unusual interest because of its asymmetric character. The analytic continuation of the scattering matrix in the momentum representation has a branch cut and an infinite number of simple poles on the negative imaginary axis which are related with the so called anti-bound states. This model does not show resonances. Using the wave functions of the anti-bound states, we obtain supersymmetric (SUSY) partners which are the series of Rosen–Morse II potentials. We have computed the Wigner reflection and transmission time delays formore » the hyperbolic step and such SUSY partners. Our results show that the more bound states a partner Hamiltonian has the smaller is the time delay. We also have evaluated time delays for the hyperbolic step potential in the classical case and have obtained striking similitudes with the quantum case. - Highlights: • The scattering matrix of hyperbolic step potential is studied. • The scattering matrix has a branch cut and an infinite number of poles. • The poles are associated to anti-bound states. • Susy partners using antibound states are computed. • Wigner time delays for the hyperbolic step and partner potentials are compared.« less

Developmental and gut-related changes to microbiomes of the cultured juvenile spiny lobster Panulirus ornatus.

PubMed

Ooi, Mei C; Goulden, Evan F; Smith, Gregory G; Nowak, Barbara F; Bridle, Andrew R

2017-12-01

With recent technologies making it possible for commercial scale closed life-cycle aquaculture production of spiny lobster (Panulirus ornatus) comes a strong impetus to further understand aspects of lobster health. The gut microbiome plays a crucial role in host health, affecting growth, digestion, immune responses and pathogen resistance. Herein we characterise and compare gut microbiomes across different developmental stages (6-7 days post-emergence [dpe], 52 dpe and 13 months post-emergence [mpe]) and gut regions (foregut, midgut and hindgut) of cultured P. ornatus juveniles. Gut samples were analysed using 16S rRNA next-generation sequencing. Core gut microbiomes of P. ornatus comprised the phyla Tenericutes and Proteobacteria. Within class Gammaproteobacteria, families Pseudoalteromonadaceae and Vibrionaceae were dominant members across the majority of the gut microbiomes. Characterisation of bacterial communities from 13 mpe lobsters indicated that the hindgut microbiome was more diverse and compositionally dissimilar to the foregut and midgut. The bacterial composition of the hindgut was more similar among younger juveniles (6-7 dpe and 52 dpe) compared to 13 mpe lobsters. This is the first study to explore gut microbiomes of spiny lobster juveniles. We demonstrate that the composition of the gut microbiome was shaped by gut region, whereas the structure of the hindgut microbiome was influenced by developmental stage. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Should We Care that Johnny Can't Catch and Susie Can't Skip? What Should We Do about It?

ERIC Educational Resources Information Center

Whitall, Jill; Clark, Jane E.

2011-01-01

Physical and sport educators care that Johnny and Susie cannot move as well as their peers. They try their best to improve their skill levels because they value participation and skillfulness in sport and physical activity. However, many times there is a deeper problem as to why Johnny or Susie cannot move as well as their peers. Physical and…

On inflation, cosmological constant, and SUSY breaking

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linde, Andrei

2016-11-02

We consider a broad class of inflationary models of two unconstrained chiral superfields, the stabilizer S and the inflaton Φ, which can describe inflationary models with nearly arbitrary potentials. These models include, in particular, the recently introduced theories of cosmological attractors, which provide an excellent fit to the latest Planck data. We show that by adding to the superpotential of the fields S and Φ a small term depending on a nilpotent chiral superfield P one can break SUSY and introduce a small cosmological constant without affecting main predictions of the original inflationary scenario.

Diminution of the gut resistome after a gut microbiota-targeted dietary intervention in obese children.

PubMed

Wu, Guojun; Zhang, Chenhong; Wang, Jing; Zhang, Feng; Wang, Ruirui; Shen, Jian; Wang, Linghua; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping; Zhang, Menghui

2016-04-05

The gut microbiome represents an important reservoir of antibiotic resistance genes (ARGs). Effective methods are urgently needed for managing the gut resistome to fight against the antibiotic resistance threat. In this study, we show that a gut microbiota-targeted dietary intervention, which shifts the dominant fermentation of gut bacteria from protein to carbohydrate, significantly diminished the gut resistome and alleviated metabolic syndrome in obese children. Of the non-redundant metagenomic gene catalog of ~2 × 10(6) microbial genes, 399 ARGs were identified in 131 gene types and conferred resistance to 47 antibiotics. Both the richness and diversity of the gut resistome were significantly reduced after the intervention. A total of 201 of the 399 ARGs were carried in 120 co-abundance gene groups (CAGs) directly binned from the gene catalog across both pre-and post-intervention samples. The intervention significantly reduced several CAGs in Klebsiella, Enterobacter and Escherichia, which were the major hubs for multiple resistance gene types. Thus, dietary intervention may become a potentially effective method for diminishing the gut resistome.

Gut-derived commensal bacterial products inhibit liver dendritic cell maturation by stimulating hepatic interleukin-6/signal transducer and activator of transcription 3 activity.

PubMed

Lunz, John G; Specht, Susan M; Murase, Noriko; Isse, Kumiko; Demetris, Anthony J

2007-12-01

Intraorgan dendritic cells (DCs) monitor the environment and help translate triggers of innate immunity into adaptive immune responses. Liver-based DCs are continually exposed, via gut-derived portal venous blood, to potential antigens and bacterial products that can trigger innate immunity. However, somehow the liver avoids a state of perpetual inflammation and protects central immune organs from overstimulation. In this study, we tested the hypothesis that hepatic interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) activity increases the activation/maturation threshold of hepatic DCs toward innate immune signals. The results show that the liver nuclear STAT3 activity is significantly higher than that of other organs and is IL-6-dependent. Hepatic DCs in normal IL-6 wild-type (IL-6(+/+)) mice are phenotypically and functionally less mature than DCs from IL-6-deficient (IL-6(-/-)) or STAT3-inhibited IL-6(+/+) mice, as determined by surface marker expression, proinflammatory cytokine secretion, and allogeneic T-cell stimulation. IL-6(+/+) liver DCs produce IL-6 in response to exposure to lipopolysaccharide (LPS) and cytidine phosphate guanosine oligonucleotides (CpG) but are resistant to maturation compared with IL-6(-/-) liver DCs. Conversely, exogenous IL-6 inhibits LPS-induced IL-6(-/-) liver DC maturation. IL-6/STAT3 signaling influences the liver DC expression of toll-like receptor 9 and IL-1 receptor associated kinase-M. The depletion of gut commensal bacteria in IL-6(+/+) mice with oral antibiotics decreased portal blood endotoxin levels, lowered the expression of IL-6 and phospho-STAT3, and significantly increased liver DC maturation. Gut-derived bacterial products, by stimulating hepatic IL-6/STAT3 signaling, inhibit hepatic DC activation/maturation and thereby elevate the threshold needed for translating triggers of innate immunity into adaptive immune responses. Manipulating gut bacteria may therefore be an effective strategy

Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health.

PubMed

Jost, Ted; Lacroix, Christophe; Braegger, Christian; Chassard, Christophe

2015-07-01

Neonatal gut microbiota establishment represents a crucial stage for gut maturation, metabolic and immunologic programming, and consequently short- and long-term health status. Human milk beneficially influences this process due to its dynamic profile of age-adapted nutrients and bioactive components and by providing commensal maternal bacteria to the neonatal gut. These include Lactobacillus spp., as well as obligate anaerobes such as Bifidobacterium spp., which may originate from the maternal gut via an enteromammary pathway as a novel form of mother-neonate communication. Additionally, human milk harbors a broad range of oligosaccharides that promote the growth and activity of specific bacterial populations, in particular, Bifidobacterium and Bacteroides spp. This review focuses on the diversity and origin of human milk bacteria, as well as on milk oligosaccharides that influence neonatal gut microbiota establishment. This knowledge can be used to develop infant formulae that more closely mimic nature's model and sustain a healthy gut microbiota. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comments on SUSY Inflation Models on the Brane

NASA Astrophysics Data System (ADS)

Lee, Lu-Yun; Cheung, Kingman; Lin, Chia-Min

In this paper we consider a class of inflation models on the brane where the dominant part of the inflaton scalar potential does not depend on the inflaton field value during inflation. In particular, we consider supernatural inflation, its hilltop version, A-term inflation, and supersymmetric (SUSY) D- and F-term hybrid inflation on the brane. We show that the parameter space can be broadened, the inflation scale generally can be lowered, and still possible to have the spectral index ns = 0.96.

Escherichia coli Probiotic Strain ED1a in Pigs Has a Limited Impact on the Gut Carriage of Extended-Spectrum-β-Lactamase-Producing E. coli

PubMed Central

Mourand, G.; Paboeuf, F.; Fleury, M. A.; Jouy, E.; Bougeard, S.; Denamur, E.

2016-01-01

ABSTRACT Four trials were conducted to evaluate the impact of Escherichia coli probiotic strain ED1a administration to pigs on the gut carriage or survival in manure of extended-spectrum-β-lactamase-producing E. coli. Groups of pigs were orally inoculated with strain E. coli M63 carrying the blaCTX-M-1 gene (n = 84) or used as a control (n = 26). In the first two trials, 24 of 40 E. coli M63-inoculated pigs were given E. coli ED1a orally for 6 days starting 8 days after oral inoculation. In the third trial, 10 E. coli M63-inoculated pigs were given either E. coli ED1a or probiotic E. coli Nissle 1917 for 5 days. In the fourth trial, E. coli ED1a was given to a sow and its 12 piglets, and these 12 piglets plus 12 piglets that had not received E. coli ED1a were then inoculated with E. coli M63. Fecal shedding of cefotaxime-resistant Enterobacteriaceae (CTX-RE) was studied by culture, and blaCTX-M-1 genes were quantified by PCR. The persistence of CTX-RE in manure samples from inoculated pigs or manure samples inoculated in vitro with E. coli M63 with or without probiotics was studied. The results showed that E. coli M63 and ED1a were good gut colonizers. The reduction in the level of fecal excretion of CTX-RE in E. coli ED1a-treated pigs compared to that in nontreated pigs was usually less than 1 log10 CFU and was mainly observed during the probiotic administration period. The results obtained with E. coli Nissle 1917 did not differ significantly from those obtained with E. coli ED1a. CTX-RE survival did not differ significantly in manure samples with or without probiotic treatment. In conclusion, under our experimental conditions, E. coli ED1a and E. coli Nissle 1917 could not durably prevent CTX-RE colonization of the pig gut. PMID:27795372

Escherichia coli Probiotic Strain ED1a in Pigs Has a Limited Impact on the Gut Carriage of Extended-Spectrum-β-Lactamase-Producing E. coli.

PubMed

Mourand, G; Paboeuf, F; Fleury, M A; Jouy, E; Bougeard, S; Denamur, E; Kempf, I

2017-01-01

Four trials were conducted to evaluate the impact of Escherichia coli probiotic strain ED1a administration to pigs on the gut carriage or survival in manure of extended-spectrum-β-lactamase-producing E. coli Groups of pigs were orally inoculated with strain E. coli M63 carrying the bla CTX-M-1 gene (n = 84) or used as a control (n = 26). In the first two trials, 24 of 40 E. coli M63-inoculated pigs were given E. coli ED1a orally for 6 days starting 8 days after oral inoculation. In the third trial, 10 E. coli M63-inoculated pigs were given either E. coli ED1a or probiotic E. coli Nissle 1917 for 5 days. In the fourth trial, E. coli ED1a was given to a sow and its 12 piglets, and these 12 piglets plus 12 piglets that had not received E. coli ED1a were then inoculated with E. coli M63. Fecal shedding of cefotaxime-resistant Enterobacteriaceae (CTX-RE) was studied by culture, and bla CTX-M-1 genes were quantified by PCR. The persistence of CTX-RE in manure samples from inoculated pigs or manure samples inoculated in vitro with E. coli M63 with or without probiotics was studied. The results showed that E. coli M63 and ED1a were good gut colonizers. The reduction in the level of fecal excretion of CTX-RE in E. coli ED1a-treated pigs compared to that in nontreated pigs was usually less than 1 log 10 CFU and was mainly observed during the probiotic administration period. The results obtained with E. coli Nissle 1917 did not differ significantly from those obtained with E. coli ED1a. CTX-RE survival did not differ significantly in manure samples with or without probiotic treatment. In conclusion, under our experimental conditions, E. coli ED1a and E. coli Nissle 1917 could not durably prevent CTX-RE colonization of the pig gut. Copyright © 2016 American Society for Microbiology.

Regulation of Lactobacillus casei Sorbitol Utilization Genes Requires DNA-Binding Transcriptional Activator GutR and the Conserved Protein GutM▿

PubMed Central

Alcántara, Cristina; Sarmiento-Rubiano, Luz Adriana; Monedero, Vicente; Deutscher, Josef; Pérez-Martínez, Gaspar; Yebra, María J.

2008-01-01

Sequence analysis of the five genes (gutRMCBA) downstream from the previously described sorbitol-6-phosphate dehydrogenase-encoding Lactobacillus casei gutF gene revealed that they constitute a sorbitol (glucitol) utilization operon. The gutRM genes encode putative regulators, while the gutCBA genes encode the EIIC, EIIBC, and EIIA proteins of a phosphoenolpyruvate-dependent sorbitol phosphotransferase system (PTSGut). The gut operon is transcribed as a polycistronic gutFRMCBA messenger, the expression of which is induced by sorbitol and repressed by glucose. gutR encodes a transcriptional regulator with two PTS-regulated domains, a galactitol-specific EIIB-like domain (EIIBGat domain) and a mannitol/fructose-specific EIIA-like domain (EIIAMtl domain). Its inactivation abolished gut operon transcription and sorbitol uptake, indicating that it acts as a transcriptional activator. In contrast, cells carrying a gutB mutation expressed the gut operon constitutively, but they failed to transport sorbitol, indicating that EIIBCGut negatively regulates GutR. A footprint analysis showed that GutR binds to a 35-bp sequence upstream from the gut promoter. A sequence comparison with the presumed promoter region of gut operons from various firmicutes revealed a GutR consensus motif that includes an inverted repeat. The regulation mechanism of the L. casei gut operon is therefore likely to be operative in other firmicutes. Finally, gutM codes for a conserved protein of unknown function present in all sequenced gut operons. A gutM mutant, the first constructed in a firmicute, showed drastically reduced gut operon expression and sorbitol uptake, indicating a regulatory role also for GutM. PMID:18676710

Potential Mechanism of Detoxification of Cyanide Compounds by Gut Microbiomes of Bamboo-Eating Pandas

PubMed Central

2018-01-01

ABSTRACT Gut microbes can enhance the ability of hosts to consume secondary plant compounds and, therefore, expand the dietary niche breadth of mammalian herbivores. The giant and red pandas are bamboo-eating specialists within the mammalian order Carnivora. Bamboo contains abundant plant secondary metabolites (e.g., cyanide-containing compounds). However, Carnivora species, including the giant panda, have deficient levels of rhodanese (one of the essential cyanide detoxification enzymes) in their tissues compared with the same tissues of herbivores. Here, we make a comparative analysis of 94 gut metagenomes, including 25 from bamboo-eating pandas (19 from giant pandas and 6 from red pandas), 30 from Père David’s deer, and 39 from published data for other mammals. The bamboo-eating pandas’ gut microbiomes had some common features, such as high proportions of Pseudomonas bacteria. The results revealed that bamboo-eating pandas’ gut microbiomes were significantly enriched in putative genes coding for enzymes related to cyanide degradation (e.g., rhodanese) compared with the gut microbiomes of typical herbivorous mammals, which might have coevolved with their special bamboo diets. The enrichment of putative cyanide-digesting gut microbes, in combination with adaptations related to morphology (e.g., pseudothumbs) and genomic signatures, show that the giant panda and red panda have evolved some common traits to adapt to their bamboo diet. IMPORTANCE The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens), two obligate bamboo feeders, have distinct phylogenetic positions in the order Carnivora. Bamboo is extraordinarily rich in plant secondary metabolites, such as allied phenolic and polyphenolic compounds and even toxic cyanide compounds. Here, the enrichment of putative cyanide-digesting gut microbes, in combination with adaptations related to morphology (e.g., pseudothumbs) and genomic signatures, show that the giant panda and red panda have

Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia.

PubMed

Daulatzai, Mak Adam

2015-01-01

The non-celiac gluten sensitivity (NCGS) is a chronic functional gastrointestinal disorder which is very common world wide. The human gut harbors microbiota which has a wide variety of microbial organisms; they are mainly symbiotic and important for well being. However, "dysbiosis" - i.e. an alteration in normal commensal gut microbiome with an increase in pathogenic microbes, impacts homeostasis/health. Dysbiosis in NCGS causes gut inflammation, diarrhea, constipation, visceral hypersensitivity, abdominal pain, dysfunctional metabolic state, and peripheral immune and neuro-immune communication. Thus, immune-mediated gut and extra-gut dysfunctions, due to gluten sensitivity with comorbid diarrhea, may last for decades. A significant proportion of NCGS patients may chronically consume alcohol, non-steroidal anti-inflammatory drugs, and fatty diet, as well as suffer from various comorbid disorders. The above pathophysiological substrate and dysbiosis are underpinned by dysfunctional bidirectional "Gut-Brain Axis" pathway. Pathogenic gut microbiota is known to upregulate gut- and systemic inflammation (due to lipopolysaccharide from pathogenic bacteria and synthesis of pro-inflammatory cytokines); they enhance energy harvest, cause obesity, insulin resistance, and dysfunctional vago-vagal gut-brain axis. Conceivably, the above cascade of pathology may promote various pathophysiological mechanisms, neuroinflammation, and cognitive dysfunction. Hence, dysbiosis, gut inflammation, and chronic dyshomeostasis are of great clinical relevance. It is argued here that we need to be aware of NCGS and its chronic pathophysiological impact. Therapeutic measures including probiotics, vagus nerve stimulation, antioxidants, alpha 7 nicotinic receptor agonists, and corticotropin-releasing factor receptor 1 antagonist may ameliorate neuroinflammation and oxidative stress in NCGS; they may therefore, prevent cognitive dysfunction and vulnerability to Alzheimer's disease.

Immune Response of Chicken Gut to Natural Colonization by Gut Microflora and to Salmonella enterica Serovar Enteritidis Infection ▿

PubMed Central

Crhanova, Magdalena; Hradecka, Helena; Faldynova, Marcela; Matulova, Marta; Havlickova, Hana; Sisak, Frantisek; Rychlik, Ivan

2011-01-01

In commercial poultry production, there is a lack of natural flora providers since chickens are hatched in the clean environment of a hatchery. Events occurring soon after hatching are therefore of particular importance, and that is why we were interested in the development of the gut microbial community, the immune response to natural microbial colonization, and the response to Salmonella enterica serovar Enteritidis infection as a function of chicken age. The complexity of chicken gut microbiota gradually increased from day 1 to day 19 of life and consisted of Proteobacteria and Firmicutes. For the first 3 days of life, chicken cecum was protected by increased expression of chicken β-defensins (i.e., gallinacins 1, 2, 4, and 6), expression of which dropped from day 4 of life. On the other hand, a transient increase in interleukin-8 (IL-8) and IL-17 expression could be observed in chicken cecum on day 4 of life, indicating physiological inflammation and maturation of the gut immune system. In agreement, the response of chickens infected with S. Enteritidis on days 1, 4, and 16 of life shifted from Th1 (characterized mainly by induction of gamma interferon [IFN-γ] and inducible nitric oxide synthase [iNOS]), observed in younger chickens, to Th17, observed in 16-day-old chickens (characterized mainly by IL-17 induction). Active modification of chicken gut microbiota in the future may accelerate or potentiate the maturation of the gut immune system and increase its resistance to infection with different pathogens. PMID:21555397

Human gut microbiota and healthy aging: Recent developments and future prospective.

PubMed

Kumar, Manish; Babaei, Parizad; Ji, Boyang; Nielsen, Jens

2016-10-27

The human gut microbiota alters with the aging process. In the first 2-3 years of life, the gut microbiota varies extensively in composition and metabolic functions. After this period, the gut microbiota demonstrates adult-like more stable and diverse microbial species. However, at old age, deterioration of physiological functions of the human body enforces the decrement in count of beneficial species (e.g. Bifidobacteria ) in the gut microbiota, which promotes various gut-related diseases (e.g. inflammatory bowel disease). Use of plant-based diets and probiotics/prebiotics may elevate the abundance of beneficial species and prevent gut-related diseases. Still, the connections between diet, microbes, and host are only partially known. To this end, genome-scale metabolic modeling can help to explore these connections as well as to expand the understanding of the metabolic capability of each species in the gut microbiota. This systems biology approach can also predict metabolic variations in the gut microbiota during ageing, and hereby help to design more effective probiotics/prebiotics.

Composition and immuno-stimulatory properties of extracellular DNA from mouse gut flora.

PubMed

Qi, Ce; Li, Ya; Yu, Ren-Qiang; Zhou, Sheng-Li; Wang, Xing-Guo; Le, Guo-Wei; Jin, Qing-Zhe; Xiao, Hang; Sun, Jin

2017-11-28

To demonstrate that specific bacteria might release bacterial extracellular DNA (eDNA) to exert immunomodulatory functions in the mouse small intestine. Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of eDNA in the mucus layers of the small intestine and colon in healthy Male C57BL/6 mice. Composition difference of eDNA and intracellular DNA (iDNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism (T-RFLP). Stimulation of cytokine production by eDNA was studied in RAW264.7 cells in vitro . TOTO-1 iodide staining confirmed existence of eDNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the eDNA in the small intestinal mucus was significantly different from that of the iDNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the eDNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Gram-positive bacteria. Both eDNA and iDNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The eDNA induced significantly lower tumor necrosis factor-α/interleukin-10 (IL-10) and IL-6/IL-10 ratios than iDNA, suggesting the predominance for maintaining immune homeostasis of the gut. Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.

Ancient acquisition of "alginate utilization loci" by human gut microbiota.

PubMed

Mathieu, Sophie; Touvrey-Loiodice, Mélanie; Poulet, Laurent; Drouillard, Sophie; Vincentelli, Renaud; Henrissat, Bernard; Skjåk-Bræk, Gudmund; Helbert, William

2018-05-23

In bacteria from the phylum Bacteroidetes, the genes coding for enzymes involved in polysaccharide degradation are often colocalized and coregulated in so-called "polysaccharide utilization loci" (PULs). PULs dedicated to the degradation of marine polysaccharides (e.g. laminaran, ulvan, alginate and porphyran) have been characterized in marine bacteria. Interestingly, the gut microbiome of Japanese individuals acquired, by lateral transfer from marine bacteria, the genes involved in the breakdown of porphyran, the cell wall polysaccharide of the red seaweed used in maki. Sequence similarity analyses predict that the human gut microbiome also encodes enzymes for the degradation of alginate, the main cell wall polysaccharide of brown algae. We undertook the functional characterization of diverse polysaccharide lyases from family PL17, frequently found in marine bacteria as well as those of human gut bacteria. We demonstrate here that this family is polyspecific. Our phylogenetic analysis of family PL17 reveals that all alginate lyases, which have all the same specificity and mode of action, cluster together in a very distinct subfamily. The alginate lyases found in human gut bacteria group together in a single clade which is rooted deeply in the PL17 tree. These enzymes were found in PULs containing PL6 enzymes, which also clustered together in the phylogenetic tree of PL6. Together, biochemical and bioinformatics analyses suggest that acquisition of this system appears ancient and, because only traces of two successful transfers were detected upon inspection of PL6 and PL17 families, the pace of acquisition of marine polysaccharide degradation system is probably very slow.

Longer guts and higher food quality increase energy intake in migratory swans.

PubMed

van Gils, Jan A; Beekman, Jan H; Coehoorn, Pieter; Corporaal, Els; Dekkers, Ten; Klaassen, Marcel; van Kraaij, Rik; de Leeuw, Rinze; de Vries, Peter P

2008-11-01

1. Within the broad field of optimal foraging, it is increasingly acknowledged that animals often face digestive constraints rather than constraints on rates of food collection. This therefore calls for a formalization of how animals could optimize food absorption rates. 2. Here we generate predictions from a simple graphical optimal digestion model for foragers that aim to maximize their (true) metabolizable food intake over total time (i.e. including nonforaging bouts) under a digestive constraint. 3. The model predicts that such foragers should maintain a constant food retention time, even if gut length or food quality changes. For phenotypically flexible foragers, which are able to change the size of their digestive machinery, this means that an increase in gut length should go hand in hand with an increase in gross intake rate. It also means that better quality food should be digested more efficiently. 4. These latter two predictions are tested in a large avian long-distance migrant, the Bewick's swan (Cygnus columbianus bewickii), feeding on grasslands in its Dutch wintering quarters. 5. Throughout winter, free-ranging Bewick's swans, growing a longer gut and experiencing improved food quality, increased their gross intake rate (i.e. bite rate) and showed a higher digestive efficiency. These responses were in accordance with the model and suggest maintenance of a constant food retention time. 6. These changes doubled the birds' absorption rate. Had only food quality changed (and not gut length), then absorption rate would have increased by only 67%; absorption rate would have increased by only 17% had only gut length changed (and not food quality). 7. The prediction that gross intake rate should go up with gut length parallels the mechanism included in some proximate models of foraging that feeding motivation scales inversely to gut fullness. We plea for a tighter integration between ultimate and proximate foraging models.

Maternal group B Streptococcus and the infant gut microbiota.

PubMed

Cassidy-Bushrow, A E; Sitarik, A; Levin, A M; Lynch, S V; Havstad, S; Ownby, D R; Johnson, C C; Wegienka, G

2016-02-01

Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant's diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R 2=0.008, P=0.008; Unweighted UniFrac R 2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.

High dietary zinc feeding promotes persistence of multi-resistant E. coli in the swine gut.

PubMed

Ciesinski, Lisa; Guenther, Sebastian; Pieper, Robert; Kalisch, Martin; Bednorz, Carmen; Wieler, Lothar H

2018-01-01

High levels of zinc oxide are used frequently as feed additive in pigs to improve gut health and growth performance and are still suggested as an alternative to antimicrobial growth promoters. However, we have recently described an increase of multi-resistant E. coli in association to zinc feeding in piglets. This previous study focused on clonal diversity of E. coli, observing the effect on multi-resistant strains by chance. To shed further light into this highly important topic and falsify our previous findings, we performed a zinc pig feeding trial where we specifically focused on in-depth analysis of antimicrobial resistant E. coli. Under controlled experimental conditions, piglets were randomly allocated to a high dietary zinc (zinc group) and a background zinc feeding group (control group). At different ages samples were taken from feces, digesta, and mucosa and absolute E. coli numbers were determined. A total of 2665 E. coli isolates were than phenotypically tested for antimicrobial resistance and results were confirmed by minimum inhibitory concentration testing for random samples. In piglets fed with high dietary zinc, we detected a substantial increase of multi-resistant E. coli in all gut habitats tested, ranging from 28.9-30.2% multi-resistant E. coli compared to 5.8-14.0% in the control group. This increase was independent of the total number of E. coli. Interestingly, the total amount of the E. coli population decreased over time. Thus, the increase of the multi-resistant E. coli populations seems to be linked with persistence of the resistant population, caused by the influence of high dietary zinc feeding. In conclusion, these findings corroborate our previous report linking high dietary zinc feeding of piglets with the occurrence of antimicrobial resistant E. coli and therefore question the feeding of high dietary zinc oxide as alternative to antimicrobial growth promoters.

High dietary zinc feeding promotes persistence of multi-resistant E. coli in the swine gut

PubMed Central

Guenther, Sebastian; Pieper, Robert; Kalisch, Martin; Bednorz, Carmen; Wieler, Lothar H.

2018-01-01

High levels of zinc oxide are used frequently as feed additive in pigs to improve gut health and growth performance and are still suggested as an alternative to antimicrobial growth promoters. However, we have recently described an increase of multi-resistant E. coli in association to zinc feeding in piglets. This previous study focused on clonal diversity of E. coli, observing the effect on multi-resistant strains by chance. To shed further light into this highly important topic and falsify our previous findings, we performed a zinc pig feeding trial where we specifically focused on in-depth analysis of antimicrobial resistant E. coli. Under controlled experimental conditions, piglets were randomly allocated to a high dietary zinc (zinc group) and a background zinc feeding group (control group). At different ages samples were taken from feces, digesta, and mucosa and absolute E. coli numbers were determined. A total of 2665 E. coli isolates were than phenotypically tested for antimicrobial resistance and results were confirmed by minimum inhibitory concentration testing for random samples. In piglets fed with high dietary zinc, we detected a substantial increase of multi-resistant E. coli in all gut habitats tested, ranging from 28.9–30.2% multi-resistant E. coli compared to 5.8–14.0% in the control group. This increase was independent of the total number of E. coli. Interestingly, the total amount of the E. coli population decreased over time. Thus, the increase of the multi-resistant E. coli populations seems to be linked with persistence of the resistant population, caused by the influence of high dietary zinc feeding. In conclusion, these findings corroborate our previous report linking high dietary zinc feeding of piglets with the occurrence of antimicrobial resistant E. coli and therefore question the feeding of high dietary zinc oxide as alternative to antimicrobial growth promoters. PMID:29373597

Human gut microbiota and healthy aging: Recent developments and future prospective

PubMed Central

Kumar, Manish; Babaei, Parizad; Ji, Boyang; Nielsen, Jens

2016-01-01

The human gut microbiota alters with the aging process. In the first 2-3 years of life, the gut microbiota varies extensively in composition and metabolic functions. After this period, the gut microbiota demonstrates adult-like more stable and diverse microbial species. However, at old age, deterioration of physiological functions of the human body enforces the decrement in count of beneficial species (e.g. Bifidobacteria) in the gut microbiota, which promotes various gut-related diseases (e.g. inflammatory bowel disease). Use of plant-based diets and probiotics/prebiotics may elevate the abundance of beneficial species and prevent gut-related diseases. Still, the connections between diet, microbes, and host are only partially known. To this end, genome-scale metabolic modeling can help to explore these connections as well as to expand the understanding of the metabolic capability of each species in the gut microbiota. This systems biology approach can also predict metabolic variations in the gut microbiota during ageing, and hereby help to design more effective probiotics/prebiotics. PMID:28035338

Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal.

PubMed

Kanwar, Jagat R; Kanwar, Rupinder K

2009-01-31

Enprocal is a high-protein micro-nutrient rich formulated supplementary food designed to meet the nutritional needs of the frail elderly and be delivered to them in every day foods. We studied the potential of Enprocal to improve gut and immune health using simple and robust bioassays for gut cell proliferation, intestinal integrity/permeability, immunomodulatory, anti-inflammatory and anti-oxidative activities. Effects of Enprocal were compared with whey protein concentrate 80 (WPC), heat treated skim milk powder, and other commercially available milk derived products. Enprocal (undigested) and digested (Enprocal D) selectively enhanced cell proliferation in normal human intestinal epithelial cells (FHs74-Int) and showed no cytotoxicity. In a dose dependent manner Enprocal induced cell death in Caco-2 cells (human colon adencarcinoma epithelial cells). Digested Enprocal (Enprocal D: gut enzyme cocktail treated) maintained the intestinal integrity in transepithelial resistance (TEER) assay, increased the permeability of horseradish peroxidase (HRP) and did not induce oxidative stress to the gut epithelial cells. Enprocal D upregulated the surface expression of co-stimulatory (CD40, CD86, CD80), MHC I and MHC II molecules on PMA differentiated THP-1 macrophages in coculture transwell model, and inhibited the monocyte/lymphocyte (THP-1/Jurkat E6-1 cells)-epithelial cell adhesion. In cytokine secretion analyses, Enprocal D down-regulated the secretion of proinflammatory cytokines (IL-1beta and TNF-alpha) and up-regulated IFN-gamma, IL-2 and IL-10. Our results indicate that Enprocal creates neither oxidative injury nor cytotoxicity, stimulates normal gut cell proliferation, up regulates immune cell activation markers and may aid in the production of antibodies. Furthermore, through downregulation of proinflammatory cytokines, Enprocal appears to be beneficial in reducing the effects of chronic gut inflammatory diseases such as inflammatory bowel disease (IBD

How gut transcriptional function of Drosophila melanogaster varies with the presence and composition of the gut microbiota.

PubMed

Bost, Alyssa; Franzenburg, Soeren; Adair, Karen L; Martinson, Vincent G; Loeb, Greg; Douglas, Angela E

2018-04-01

Despite evidence from laboratory experiments that perturbation of the gut microbiota affects many traits of the animal host, our understanding of the effect of variation in microbiota composition on animals in natural populations is very limited. The core purpose of this study on the fruit fly Drosophila melanogaster was to identify the impact of natural variation in the taxonomic composition of gut bacterial communities on host traits, with the gut transcriptome as a molecular index of microbiota-responsive host traits. Use of the gut transcriptome was validated by demonstrating significant transcriptional differences between the guts of laboratory flies colonized with bacteria and maintained under axenic conditions. Wild Drosophila from six field collections made over two years had gut bacterial communities of diverse composition, dominated to varying extents by Acetobacteraceae and Enterobacteriaceae. The gut transcriptomes also varied among collections and differed markedly from those of laboratory flies. However, no overall relationship between variation in the wild fly transcriptome and taxonomic composition of the gut microbiota was evident at all taxonomic scales of bacteria tested for both individual fly genes and functional categories in Gene Ontology. We conclude that the interaction between microbiota composition and host functional traits may be confounded by uncontrolled variation in both ecological circumstance and host traits (e.g., genotype, age physiological condition) under natural conditions, and that microbiota effects on host traits identified in the laboratory should, therefore, be extrapolated to field population with great caution. © 2017 John Wiley & Sons Ltd.

Neutrino masses and mixings as an evidence of GUT, and the impact to (flavor changing) nucleon decay

NASA Astrophysics Data System (ADS)

Maekawa, Nobuhiro; Muramatsu, Yu

2017-11-01

First, we see that the observed data of quark and lepton masses and mixings, which has been completed by adding neutrino data, can be a qualitative signature of S U(5) grand unified theory (GUT). Actually, an assumption, 10 fields induce stronger hierarchy in Yukawa couplings than 5 ¯ fields, can explain all hierarchical structures of quark and lepton masses and mixings. Second, we see the attractiveness of E6 GUT, in which the above assumption in S U(5) GUT can be derived and as the result various Yukawa hierarchies of quarks and leptons can be obtained from only one basic hierarchy. Third, we compare the predictions for nucleon decay among several GUTs with S U(5), S O(10), and E6 unification group which satisfy the above important assumption for Yukawa hierarchy, since this understanding about Yukawa structures reduces the ambiguities in prediction of nucleon decay via superheavy gauge boson exchange. We stress the importance of observations for several decay modes. One of them is flavor changing nucleon decay, for example, P → π0 µ+, which is the decay mode that SuperKamiokande has reported two events in the signal region. This article is based on our works in Ref.[1, 2

Gut dysbiosis impairs recovery after spinal cord injury

PubMed Central

Wang, Lingling; Mo, Xiaokui

2016-01-01

The trillions of microbes that exist in the gastrointestinal tract have emerged as pivotal regulators of mammalian development and physiology. Disruption of this gut microbiome, a process known as dysbiosis, causes or exacerbates various diseases, but whether gut dysbiosis affects recovery of neurological function or lesion pathology after traumatic spinal cord injury (SCI) is unknown. Data in this study show that SCI increases intestinal permeability and bacterial translocation from the gut. These changes are associated with immune cell activation in gut-associated lymphoid tissues (GALTs) and significant changes in the composition of both major and minor gut bacterial taxa. Postinjury changes in gut microbiota persist for at least one month and predict the magnitude of locomotor impairment. Experimental induction of gut dysbiosis in naive mice before SCI (e.g., via oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment and spinal cord pathology after SCI. Conversely, feeding SCI mice commercial probiotics (VSL#3) enriched with lactic acid–producing bacteria triggers a protective immune response in GALTs and confers neuroprotection with improved locomotor recovery. Our data reveal a previously unknown role for the gut microbiota in influencing recovery of neurological function and neuropathology after SCI. PMID:27810921

Microbiota-host interplay at the gut epithelial level, health and nutrition.

PubMed

Lallès, Jean-Paul

2016-01-01

Growing evidence suggests the implication of the gut microbiota in various facets of health and disease. In this review, the focus is put on microbiota-host molecular cross-talk at the gut epithelial level with special emphasis on two defense systems: intestinal alkaline phosphatase (IAP) and inducible heat shock proteins (iHSPs). Both IAP and iHSPs are induced by various microbial structural components (e.g. lipopolysaccharide, flagellin, CpG DNA motifs), metabolites (e.g. n-butyrate) or secreted signal molecules (e.g., toxins, various peptides, polyphosphate). IAP is produced in the small intestine and secreted into the lumen and in the interior milieu. It detoxifies microbial components by dephosphorylation and, therefore, down-regulates microbe-induced inflammation mainly by inhibiting NF-κB pro-inflammatory pathway in enterocytes. IAP gene expression and enzyme activity are influenced by the gut microbiota. Conversely, IAP controls gut microbiota composition both directly, and indirectly though the detoxification of pro-inflammatory free luminal adenosine triphosphate and inflammation inhibition. Inducible HSPs are expressed by gut epithelial cells in proportion to the microbial load along the gastro-intestinal tract. They are also induced by various microbial components, metabolites and secreted molecules. Whether iHSPs contribute to shape the gut microbiota is presently unknown. Both systems display strong anti-inflammatory and anti-oxidant properties that are protective to the gut and the host. Importantly, epithelial gene expressions and protein concentrations of IAP and iHSPs can be stimulated by probiotics, prebiotics and a large variety of dietary components, including macronutrients (protein and amino acids, especially L-glutamine, fat, fiber), and specific minerals (e.g. calcium) and vitamins (e.g. vitamins K1 and K2). Some food components (e.g. lectins, soybean proteins, various polyphenols) may inhibit or disturb these systems. The general cellular

Gut microbiota may predict host divergence time during Glires evolution.

PubMed

Li, Huan; Qu, Jiapeng; Li, Tongtong; Yao, Minjie; Li, Jiaying; Li, Xiangzhen

2017-03-01

The gut microbial communities of animals play key roles in host evolution. However, the possible relationship between gut microbiota and host divergence time remains unknown. Here, we investigated the gut microbiota of eight Glires species (four lagomorph species and four rodent species) distributed throughout the Qinghai-Tibet plateau and Inner Mongolia grassland. Lagomorphs and rodents had distinct gut microbial compositions. Three out of four lagomorph species were dominated by Firmicutes, while rodents were dominated by Bacteroidetes in general. The alpha diversity values (Shannon diversity and evenness) exhibited significant differences between any two species within the lagomorphs, whereas there were no significant differences among rodents. The structure of the gut microbiota showed significant differences between lagomorphs and rodents. In addition, we calculated host phylogeny and divergence times, and used a phylogenetic approach to reconstruct how the animal gut microbiota has diverged from their ancestral species. Some core bacterial genera (e.g. Prevotella and Clostridium) shared by more than nine-tenths of all the Glires individuals associated with plant polysaccharide degradation showed marked changes within lagomorphs. Differences in Glires gut microbiota (based on weighted UniFrac and Bray-Curtis dissimilarity metrics) were positively correlated with host divergence time. Our results thus suggest the gut microbial composition is associated with host phylogeny, and further suggest that dissimilarity of animal gut microbiota may predict host divergence time. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Role of Gut Microbiota in Liver Disease.

PubMed

Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

2015-01-01

Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

Recruitment and establishment of the gut microbiome in arctic shorebirds.

PubMed

Grond, Kirsten; Lanctot, Richard B; Jumpponen, Ari; Sandercock, Brett K

2017-12-01

Gut microbiota play a key role in host health. Mammals acquire gut microbiota during birth, but timing of gut microbial recruitment in birds is unknown. We evaluated whether precocial chicks from three species of arctic-breeding shorebirds acquire gut microbiota before or after hatching, and then documented the rate and compositional dynamics of accumulation of gut microbiota. Contrary to earlier reports of microbial recruitment before hatching in chickens, quantitative PCR and Illumina sequence data indicated negligible microbiota in the guts of shorebird embryos before hatching. Analyses of chick feces indicated an exponential increase in bacterial abundance of guts 0-2 days post-hatch, followed by stabilization. Gut communities were characterized by stochastic recruitment and convergence towards a community dominated by Clostridia and Gammaproteobacteria. We conclude that guts of shorebird chicks are likely void of microbiota prior to hatch, but that stable gut microbiome establishes as early as 3 days of age, probably from environmental inocula. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gut Microbiota-brain Axis

PubMed Central

Wang, Hong-Xing; Wang, Yu-Ping

2016-01-01

Objective: To systematically review the updated information about the gut microbiota-brain axis. Data Sources: All articles about gut microbiota-brain axis published up to July 18, 2016, were identified through a literature search on PubMed, ScienceDirect, and Web of Science, with the keywords of “gut microbiota”, “gut-brain axis”, and “neuroscience”. Study Selection: All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed, with no limitation of study design. Results: It is well-recognized that gut microbiota affects the brain's physiological, behavioral, and cognitive functions although its precise mechanism has not yet been fully understood. Gut microbiota-brain axis may include gut microbiota and their metabolic products, enteric nervous system, sympathetic and parasympathetic branches within the autonomic nervous system, neural-immune system, neuroendocrine system, and central nervous system. Moreover, there may be five communication routes between gut microbiota and brain, including the gut-brain's neural network, neuroendocrine-hypothalamic-pituitary-adrenal axis, gut immune system, some neurotransmitters and neural regulators synthesized by gut bacteria, and barrier paths including intestinal mucosal barrier and blood-brain barrier. The microbiome is used to define the composition and functional characteristics of gut microbiota, and metagenomics is an appropriate technique to characterize gut microbiota. Conclusions: Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain, which may provide a new way to protect the brain in the near future. PMID:27647198

Higgs, SUSY and the standard model at /γγ colliders

NASA Astrophysics Data System (ADS)

Hagiwara, Kaoru

2001-10-01

In this report, I surveyed physics potential of the γγ option of a linear e +e - collider with the following questions in mind: What new discovery can be expected at a γγ collider in addition to what will be learned at its ' parent' e +e -linear collider? By taking account of the hard energy spectrum and polarization of colliding photons, produced by Compton back-scattering of laser light off incoming e - beams, we find that a γγ collider is most powerful when new physics appears in the neutral spin-zero channel at an invariant mass below about 80% of the c.m. energy of the colliding e -e - system. If a light Higgs boson exists, its properties can be studied in detail, and if its heavier partners or a heavy Higgs boson exists in the above mass range, they may be discovered at a γγ collider. CP property of the scalar sector can be explored in detail by making use of linear polarization of the colliding photons, decay angular correlations of final state particles, and the pattern of interference with the Standard Model amplitudes. A few comments are given for SUSY particle studies at a γγ collider, where a pair of charged spinless particles is produced in the s-wave near the threshold. Squark-onium may be discovered. An e ±γ collision mode may measure the Higgs- Z-γ coupling accurately and probe flavor oscillations in the slepton sector. As a general remark, all the Standard Model background simulation tools should be prepared in the helicity amplitude level, so that simulation can be performed for an arbitrary set of Stokes parameters of the incoming photon beams.

Compartmentalization of Inflammatory Response Following Gut Ischemia Reperfusion.

PubMed

Collange, O; Charles, A-L; Lavaux, T; Noll, E; Bouitbir, J; Zoll, J; Chakfé, N; Mertes, M; Geny, B

2015-01-01

Gut ischemia reperfusion (IR) is thought to trigger systemic inflammation, multiple organ failure, and death. The aim of this study was to investigate inflammatory responses in blood and in two target organs after gut IR. This was a controlled animal study. Adult male Wistar rats were randomized into two groups of eight rats: control group and gut IR group (60 minutes of superior mesenteric artery occlusion followed by 60 minutes of reperfusion). Lactate and four cytokines (tumor necrosis factor-a, interleukin [IL]-1b, IL-6, and IL-10) were measured in mesenteric and systemic blood. The relative gene expression of these cytokines was determined by real time polymerase chain reaction in the gut, liver, and lung. Gut IR significantly increased lactate levels in mesenteric (0.9 ± 0.4 vs. 3.7 ± 1.8 mmol/L; p < .001) and in systemic blood (1.3 ± 0.2 vs. 4.0 ± 0.3 mmol/L; p < .001). Gut IR also increased the levels of four cytokines in mesenteric and systemic blood. IL-6 and IL-10 were the main circulating cytokines; there were no significant differences between mesenteric and systemic cytokine levels. IL-10 was upregulated mainly in the lung,suggesting that this organ could play a major role during gut reperfusion. The predominance of IL-10 over other cytokines in plasma and the dissimilar organ responses,especially of the lung, might be a basis for the design of therapies, for example lung protective ventilation strategies, to limit the deleterious effects of the inflammatory cascade. A multi-organ protective approach might involve gut directed therapies, protective ventilation, hemodynamic optimization, and hydric balance.

Leptogenesis scenarios for natural SUSY with mixed axion-higgsino dark matter

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Serce, Hasan; Zhang, Yi-Fan

2016-01-01

Supersymmetric models with radiatively-driven electroweak naturalness require light higgsinos of mass ~ 100-300 GeV . Naturalness in the QCD sector is invoked via the Peccei-Quinn (PQ) axion leading to mixed axion-higgsino dark matter. The SUSY DFSZ axion model provides a solution to the SUSY μ problem and the Little Hierarchy μll m3/2 may emerge as a consequence of a mismatch between PQ and hidden sector mass scales. The traditional gravitino problem is now augmented by the axino and saxion problems, since these latter particles can also contribute to overproduction of WIMPs or dark radiation, or violation of BBN constraints. We compute regions of the TR vs. m3/2 plane allowed by BBN, dark matter and dark radiation constraints for various PQ scale choices fa. These regions are compared to the values needed for thermal leptogenesis, non-thermal leptogenesis, oscillating sneutrino leptogenesis and Affleck-Dine leptogenesis. The latter three are allowed in wide regions of parameter space for PQ scale fa~ 1010-1012 GeV which is also favored by naturalness: fa ~ √μMP/λμ ~ 1010-1012 GeV . These fa values correspond to axion masses somewhat above the projected ADMX search regions.

Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation*

PubMed Central

Gregory, Jill C.; Buffa, Jennifer A.; Org, Elin; Wang, Zeneng; Levison, Bruce S.; Zhu, Weifei; Wagner, Matthew A.; Bennett, Brian J.; Li, Lin; DiDonato, Joseph A.; Lusis, Aldons J.; Hazen, Stanley L.

2015-01-01

Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38; p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TMAO levels were initially higher in recipients on choline diet that received cecal microbes from C57BL/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMAO levels. Proportions of specific taxa were also identified that correlated with plasma TMAO levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility. PMID:25550161

How informative is the mouse for human gut microbiota research?

PubMed Central

Nguyen, Thi Loan Anh; Vieira-Silva, Sara; Liston, Adrian; Raes, Jeroen

2015-01-01

The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research. PMID:25561744

How informative is the mouse for human gut microbiota research?

PubMed

Nguyen, Thi Loan Anh; Vieira-Silva, Sara; Liston, Adrian; Raes, Jeroen

2015-01-01

The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research. © 2015. Published by The Company of Biologists Ltd.

Gut-training: the impact of two weeks repetitive gut-challenge during exercise on gastrointestinal status, glucose availability, fuel kinetics, and running performance.

PubMed

Costa, Ricardo J S; Miall, Atlanta; Khoo, Anthony; Rauch, Christopher; Snipe, Rhiannon; Camões-Costa, Vera; Gibson, Peter

2017-05-01

Due to gastrointestinal tract adaptability, the study aimed to determine the impact of gut-training protocol over 2 weeks on gastrointestinal status, blood glucose availability, fuel kinetics, and running performance. Endurance runners (n = 25) performed a gut-challenge trial (GC1), consisting of 2 h running exercise at 60% V̇O 2max whilst consuming gel-discs containing 30 g carbohydrates (2:1 glucose/fructose, 10% w/v) every 20 min and a 1 h distance test. Participants were then randomly assigned to a carbohydrate gel-disc (CHO-S), carbohydrate food (CHO-F), or placebo (PLA) gut-training group for 2 weeks of repetitive gut-challenge intervention. Participants then repeated a second gut-challenge trial (GC2). Gastrointestinal symptoms reduced in GC2 on CHO-S (60%; p = 0.008) and CHO-F (63%; p = 0.046); reductions were greater than PLA (p < 0.05). H 2 peak was lower in GC2 on CHO-S (mean (CI): 6 (4-8) ppm) compared with CHO-F (9 (6-12) ppm) and PLA (12 (2-21) ppm) (trial × time: p < 0.001). Blood glucose concentration was higher in GC2 on CHO-S (7.2 (6.3-8.1) mmol·L -1 ) compared with CHO-F (6.1 (5.7-6.5) mmol·L -1 ) and PLA (6.2 (4.9-7.5) mmol·L -1 ) (trial × time: p = 0.015). No difference in oxidation rates, plasma I-FABP, and cortisol concentrations were observed between groups and trials. Distance test improved on CHO-S (5.2%) and CHO-F (4.3%) in GC2, but not on PLA (-2.1%) (trial × time: p = 0.009). Two weeks of gut-training with CHO-S and CHO-F improved gastrointestinal symptoms and running performance compared with PLA. CHO-S also reduced malabsorption and increased blood glucose availability during endurance running compared with PLA.

Primordial monopoles, proton decay, gravity waves and GUT inflation

DOE PAGES

Şenoğuz, Vedat Nefer; Shafi, Qaisar

2015-11-18

Here, we consider non-supersymmetric GUT inflation models in which intermediate mass monopoles may survive inflation because of the restricted number of e-foldings experienced by the accompanying symmetry breaking. Thus, an observable flux of primordial magnetic monopoles, comparable to or a few orders below the Parker limitmay be present in the galaxy. The mass scale associated with the intermediate symmetry breaking is 10 13 GeVfor an observable flux level, with the corresponding monopoles an order of magnitude or so heavier. Examples based on SO(10)and E 6 yield such intermediate mass monopoles carrying respectively two and three units of Dirac magnetic charge.more » For GUT inflation driven by a gauge singlet scalar field with a Coleman–Weinberg or Higgs potential, compatibility with the Planck measurement of the scalar spectral index yields a Hubble constant (during horizon exit of cosmological scales) H~7–9 ×10 13 GeV, with the tensor to scalar ratio rpredicted to be ≳0.02. Proton lifetime estimates for decays mediated by the superheavy gauge bosons are also provided.« less

Computational determination of the effects of virulent Escherichia coli and salmonella bacteriophages on human gut.

PubMed

Mostafa, Marwa Mostafa; Nassef, Mohammad; Badr, Amr

2016-10-01

Salmonella and Escherichia coli are different types of bacteria that cause food poisoning in humans. In the elderly, infants and people with chronic conditions, it is very dangerous if Salmonella or E. coli gets into the bloodstream and then they must be treated by phage therapy. Treating Salmonella and E. coli by phage therapy affects the gut flora. This research paper presents a system for detecting the effects of virulent E. coli and Salmonella bacteriophages on human gut. A method based on Domain-Domain Interactions (DDIs) model is implemented in the proposed system to determine the interactions between the proteins of human gut bacteria and the proteins of bacteriophages that infect virulent E. coli and Salmonella. The system helps gastroenterologists to realize the effect of injecting bacteriophages that infect virulent E. coli and Salmonella on the human gut. By testing the system over Enterobacteria phage 933W, Enterobacteria phage VT2-Sa and Enterobacteria phage P22, it resulted in four interactions between the proteins of the bacteriophages that infect E. coli O157:H7, E. coli O104:H4 and Salmonella typhimurium and the proteins of human gut bacterium strains. Several effects were detected such as: antibacterial activity against a number of bacterial species in human gut, regulation of cellular differentiation and organogenesis during gut, lung, and heart development, ammonia assimilation in bacteria, yeasts, and plants, energizing defense system and its function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in human gut. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pre-treatment with antibiotics and Escherichia coli to equalize the gut microbiota in conventional mice.

PubMed

Linninge, Caroline; Ahrné, Siv; Molin, Göran

2015-01-01

The composition of the gut microbiota can vary widely between individual mice of the same batch and thereby affect the resulting outcome in experimental studies. Therefore, an efficient method is needed to equalize the gut microbiota prior to the start of critical experiments. In order to minimize variations in gut microbiota between animals and provide the animals with a Gram-negative flora exposing lipopolysaccharides in the cell-walls, C57BL/6 mice were given a mixture of ampicillin, metronidazole and clindamycin in the drinking water for 3 days and then Escherichia coli for two additional days. Treatment with antibiotics alone or with antibiotics in combination with E. coli was well tolerated by all animals. Body weight and liver weight were not affected, although higher hepatic fat content was found in treated animals (p < 0.05). The diversity of the gut microbiota was strongly reduced in animals treated with antibiotics and antibiotics in combination with E. coli (p < 0.01), without affecting the total amount of bacteria. Cloned and sequenced 16S rRNA genes showed high presence of Enterobacteriaceae and Porphymonadaceae in the treated animals. Analysis with Principal Component Analysis gave a clear separation of the composition in microbiota between different treatment groups. The described treatment efficiently equalized the gut microbiota and provided the animals with a strong abundance of Enterobacteriaceae without changing the total load of bacteria. This is a straightforward, lenient and efficient method of pre-treatment to equalize the gut microbiota of mice as a starting procedure of animal studies.

Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice.

PubMed

van der Lugt, Benthe; Rusli, Fenni; Lute, Carolien; Lamprakis, Andreas; Salazar, Ethel; Boekschoten, Mark V; Hooiveld, Guido J; Müller, Michael; Vervoort, Jacques; Kersten, Sander; Belzer, Clara; Kok, Dieuwertje E G; Steegenga, Wilma T

2018-05-16

The aging process is associated with diminished colonic health. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp . , and a decline of the health-promoting Akkermansia spp . and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.

Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes.

PubMed

Steele, Margaret I; Kwong, Waldan K; Whiteley, Marvin; Moran, Nancy A

2017-12-12

Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi , a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared with Gilliamella apicola , a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes in Escherichia coli Using transcriptome sequencing, we demonstrate that S. alvi T6SSs and associated toxins are upregulated in the gut environment. We find that S. alvi Rhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effects in vivo Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota. IMPORTANCE The structure and composition of host-associated bacterial communities are of broad interest, because these communities affect host health. Bees have a simple, conserved gut microbiota, which provides an opportunity to explore interactions between species that have coevolved within their host over millions of

Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.

PubMed

Gao, Bei; Chi, Liang; Mahbub, Ridwan; Bian, Xiaoming; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

2017-04-17

Lead exposure remains a global public health issue, and the recent Flint water crisis has renewed public concern about lead toxicity. The toxicity of lead has been well established in a variety of systems and organs. The gut microbiome has been shown to be highly involved in many critical physiological processes, including food digestion, immune system development, and metabolic homeostasis. However, despite the key role of the gut microbiome in human health, the functional impact of lead exposure on the gut microbiome has not been studied. The aim of this study is to define gut microbiome toxicity induced by lead exposure in C57BL/6 mice using multiomics approaches, including 16S rRNA sequencing, whole genome metagenomics sequencing, and gas chromatography-mass spectrometry (GC-MS) metabolomics. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E, bile acids, nitrogen metabolism, energy metabolism, oxidative stress, and the defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications for lead toxicity in the host. Taken together, these results demonstrated that lead exposure not only altered the gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.

Multi-antioxidant supplementation does not prevent an increase in gut permeability after lower torso ischemia and reperfusion in humans.

PubMed

Wijnen, M H W A; Vader, H L; Roumen, R M H

2002-01-01

An increase in gut permeability can have serious consequences leading to sepsis and multiple organ failure. After lower torso ischemia an increase in gut permeability is seen in both animals and humans. There is proof that this can be modified by antioxidant supplementation. In this prospective, randomized study we have looked at the influence of a multiantioxidant supplementation regime, using allopurinol, vitamins E and C, mannitol and N-acetylcysteine, perioperatively. Twenty-two patients received standard treatment and 20 patients received supplementation. Gut permeability was determined using a double sugar test with lactulose and rhamnose. A significant increase in gut permeability was found neither in the non-treatment group (p = 0.012) nor in the treatment group (p = 0.006) after 6 and 24 h. No difference was found between the group receiving antioxidants and the standard treatment group. p = 0.93 6 h post clamp; p = 0.97 24 h post clamp. In this study we have not found an influence of multiantioxidant supplementation on gut permeability after lower torso ischemia. Possible explanations for this negative result are being discussed. Copyright 2002 S. Karger AG, Basel

A systems biology approach to predict and characterize human gut microbial metabolites in colorectal cancer.

PubMed

Wang, QuanQiu; Li, Li; Xu, Rong

2018-04-18

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. It is estimated that about half the cases of CRC occurring today are preventable. Recent studies showed that human gut microbiota and their collective metabolic outputs play important roles in CRC. However, the mechanisms by which human gut microbial metabolites interact with host genetics in contributing CRC remain largely unknown. We hypothesize that computational approaches that integrate and analyze vast amounts of publicly available biomedical data have great potential in better understanding how human gut microbial metabolites are mechanistically involved in CRC. Leveraging vast amount of publicly available data, we developed a computational algorithm to predict human gut microbial metabolites for CRC. We validated the prediction algorithm by showing that previously known CRC-associated gut microbial metabolites ranked highly (mean ranking: top 10.52%; median ranking: 6.29%; p-value: 3.85E-16). Moreover, we identified new gut microbial metabolites likely associated with CRC. Through computational analysis, we propose potential roles for tartaric acid, the top one ranked metabolite, in CRC etiology. In summary, our data-driven computation-based study generated a large amount of associations that could serve as a starting point for further experiments to refute or validate these microbial metabolite associations in CRC cancer.

Amoxapine Demonstrates Incomplete Inhibition of β-Glucuronidase Activity from Human Gut Microbiota.

PubMed

Yang, Wei; Wei, Bin; Yan, Ru

2018-01-01

Amoxapine has been demonstrated to be a potent inhibitor of Escherichia coli β-glucuronidase. This study aims to explore the factors causing unsatisfactory efficacy of amoxapine in alleviating CPT-11-induced gastrointestinal toxicity in mice and to predict the outcomes in humans. Amoxapine (100 µM) exhibited poor and varied inhibition on β-glucuronidase activity in gut microbiota from 10 healthy individuals and their pool (pool, 11.9%; individuals, 3.6%-54.4%) with IC 50 >100 µM and potent inhibition toward E. coli β-glucuronidase (IC 50 = 0.34 µM). p-Nitrophenol formation from p-nitrophenyl-β-D-glucuronide by pooled and individual gut microbiota fitted classical Michaelis-Menten kinetics, showing similar affinity (K m = 113-189 µM) but varied catalytic capability (V max = 53-556 nmol/h/mg). Interestingly, amoxapine showed distinct inhibitory effects (8.7%-100%) toward β-glucuronidases of 13 bacterial isolates (including four Enterococcus, three Streptococcus, two Escherichia, and two Staphylococcus strains; gus genes belonging to OTU1, 2 or 21) regardless of their genetic similarity or bacterial origin. In addition, amoxapine inhibited the growth of pooled and individual gut microbiota at a high concentration (6.3%-30.8%, 200 µM). Taken together, these findings partly explain the unsatisfactory efficacy of amoxapine in alleviating CPT-11-induced toxicity and predict a poor outcome of β-glucuronidase inhibition in humans, highlighting the necessity of using a human gut microbiota community for drug screening.

The gut microbiota, obesity and insulin resistance.

PubMed

Shen, Jian; Obin, Martin S; Zhao, Liping

2013-02-01

The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

Gut microbiota and obesity: lessons from the microbiome.

PubMed

Cani, Patrice D

2013-07-01

The distal gut harbours microbial communities that outnumber our own eukaryotic cells. The contribution of the gut microbiota to the development of several diseases (e.g. obesity, type 2 diabetes, steatosis, cardiovascular diseases and inflammatory bowel diseases) is becoming clear, although the causality remains to be proven in humans. Global changes in the gut microbiota have been observed by a number of culture-dependent and culture-independent methods, and while the latter have mostly included 16S ribosomal RNA gene analyses, more recent studies have utilized DNA sequencing of whole-microbial communities. Altogether, these high-throughput methods have facilitated the identification of novel candidate bacteria and, most importantly, metabolic functions that might be associated with obesity and type 2 diabetes. This review discusses the association between specific taxa and obesity, together with the techniques that are used to characterize the gut microbiota in the context of obesity and type 2 diabetes. Recent results are discussed in the framework of the interactions between gut microbiota and host metabolism.

Diversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes

PubMed Central

Whiteley, Marvin

2017-01-01

ABSTRACT Microbial communities are shaped by interactions among their constituent members. Some Gram-negative bacteria employ type VI secretion systems (T6SSs) to inject protein toxins into neighboring cells. These interactions have been theorized to affect the composition of host-associated microbiomes, but the role of T6SSs in the evolution of gut communities is not well understood. We report the discovery of two T6SSs and numerous T6SS-associated Rhs toxins within the gut bacteria of honey bees and bumble bees. We sequenced the genomes of 28 strains of Snodgrassella alvi, a characteristic bee gut microbe, and found tremendous variability in their Rhs toxin complements: altogether, these strains appear to encode hundreds of unique toxins. Some toxins are shared with Gilliamella apicola, a coresident gut symbiont, implicating horizontal gene transfer as a source of toxin diversity in the bee gut. We use data from a transposon mutagenesis screen to identify toxins with antibacterial function in the bee gut and validate the function and specificity of a subset of these toxin and immunity genes in Escherichia coli. Using transcriptome sequencing, we demonstrate that S. alvi T6SSs and associated toxins are upregulated in the gut environment. We find that S. alvi Rhs loci have a conserved architecture, consistent with the C-terminal displacement model of toxin diversification, with Rhs toxins, toxin fragments, and cognate immunity genes that are expressed and confer strong fitness effects in vivo. Our findings of T6SS activity and Rhs toxin diversity suggest that T6SS-mediated competition may be an important driver of coevolution within the bee gut microbiota. PMID:29233893

[Fungi in the gut - the gut mycobiome].

PubMed

Hof, Herbert

2017-08-01

Many different fungi, including yeasts and molds, can be found in the intestinal tract of humans constituting the gut mycobiome. In case the bacterial flora is altered, the fungal flora may react inversely. By a so-called fungal diet, however, the composition of the mycobiome can hardly be influenced. Whereas some fungi are only transiently present in the gut after oral uptake, others, such as Candida, Saccharomyces, Rhodotorula, Trichosporon, Geotrichum, amongst others, are members of the residential, autochthonous gut flora. Some of these fungi exert beneficial effects, for example by synthesizing useful materials. Rhodotorula can produce fatty acids and carotenoids. Others are able to metabolize toxic compounds, for example mycotoxins as well as procarcinogenic items in food. Toxins, as well as pathogenic bacteria, can be bound to mannans on the surface of fungi und can consequently be exported. Some fungi are said to exert probiotic activities. Certain fungal constituents, such as glucans, may even stimulate the immune system. On the other hand, some fungi cannot only colonize the gut asymptomatically but can also be noxious under certain conditions when, for example, the bacterial flora is disturbed. By means of their virulence factors, they can damage the gut epithelium and even penetrate into the Mukosa inducing inflammation, They can also aggravate chronic inflammatory processes. Fungi play a role in the development of obesity. Lastly, fungi in the gut represent a reservoir from which they may spread to other sites when the conditions are favorable. © Georg Thieme Verlag KG Stuttgart · New York.

Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls.

PubMed

Stewart, Christopher J; Embleton, Nicholas D; Marrs, Emma C L; Smith, Daniel P; Fofanova, Tatiana; Nelson, Andrew; Skeath, Tom; Perry, John D; Petrosino, Joseph F; Berrington, Janet E; Cummings, Stephen P

2017-07-12

Late onset sepsis (LOS) in preterm infants is associated with considerable morbidity and mortality. While studies have implicated gut bacteria in the aetiology of the disease, functional analysis and mechanistic insights are generally lacking. We performed temporal bacterial (n = 613) and metabolomic (n = 63) profiling on extensively sampled stool from 7 infants with LOS and 28 matched healthy (no LOS or NEC) controls. The bacteria isolated in diagnostic blood culture usually corresponded to the dominant bacterial genera in the gut microbiome. Longitudinal changes were monitored based on preterm gut community types (PGCTs), where control infants had an increased number of PGCTs compared to LOS infants (P = 0.011). PGCT 6, characterised by Bifidobacteria dominance, was only present in control infants. Metabolite profiles differed between LOS and control infants at diagnosis and 7 days later, but not 7 days prior to diagnosis. Bifidobacteria was positively correlated with control metabolites, including raffinose, sucrose, and acetic acid. Using multi-omic analysis, we show that the gut microbiome is involved in the pathogenesis of LOS. While the causative agent of LOS varies, it is usually abundant in the gut. Bifidobacteria dominance was associated with control infants, and the presence of this organism may directly protect, or act as a marker for protection, against gut epithelial translocation. While the metabolomic data is preliminary, the findings support that gut development and protection in preterm infants is associated with increased in prebiotic oligosaccharides (e.g. raffinose) and the growth of beneficial bacteria (e.g. Bifidobacterium).

Vacuum Stability in Split SUSY and Little Higgs Models

NASA Astrophysics Data System (ADS)

Datta, Alakabha; Zhang, Xinmin

We study the stability of the effective Higgs potential in the split supersymmetry and Little Higgs models. In particular, we study the effects of higher dimensional operators in the effective potential on the Higgs mass predictions. We find that the size and sign of the higher dimensional operators can significantly change the Higgs mass required to maintain vacuum stability in Split SUSY models. In the Little Higgs models the effects of higher dimensional operators can be large because of a relatively lower cutoff scale. Working with a specific model we find that a contribution from the higher dimensional operator with coefficient of O(1) can destabilize the vacuum.

A psychology of the human brain-gut-microbiome axis.

PubMed

Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

2017-04-01

In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

PubMed Central

Walker, Alesia; Pfitzner, Barbara; Neschen, Susanne; Kahle, Melanie; Harir, Mourad; Lucio, Marianna; Moritz, Franco; Tziotis, Dimitrios; Witting, Michael; Rothballer, Michael; Engel, Marion; Schmid, Michael; Endesfelder, David; Klingenspor, Martin; Rattei, Thomas; Castell, Wolfgang zu; de Angelis, Martin Hrabé; Hartmann, Anton; Schmitt-Kopplin, Philippe

2014-01-01

A combinatory approach using metabolomics and gut microbiome analysis techniques was performed to unravel the nature and specificity of metabolic profiles related to gut ecology in obesity. This study focused on gut and liver metabolomics of two different mouse strains, the C57BL/6J (C57J) and the C57BL/6N (C57N) fed with high-fat diet (HFD) for 3 weeks, causing diet-induced obesity in C57N, but not in C57J mice. Furthermore, a 16S-ribosomal RNA comparative sequence analysis using 454 pyrosequencing detected significant differences between the microbiome of the two strains on phylum level for Firmicutes, Deferribacteres and Proteobacteria that propose an essential role of the microbiome in obesity susceptibility. Gut microbial and liver metabolomics were followed by a combinatory approach using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and ultra performance liquid chromatography time of tlight MS/MS with subsequent multivariate statistical analysis, revealing distinctive host and microbial metabolome patterns between the C57J and the C57N strain. Many taurine-conjugated bile acids (TBAs) were significantly elevated in the cecum and decreased in liver samples from the C57J phenotype likely displaying different energy utilization behavior by the bacterial community and the host. Furthermore, several metabolite groups could specifically be associated with the C57N phenotype involving fatty acids, eicosanoids and urobilinoids. The mass differences based metabolite network approach enabled to extend the range of known metabolites to important bile acids (BAs) and novel taurine conjugates specific for both strains. In summary, our study showed clear alterations of the metabolome in the gastrointestinal tract and liver within a HFD-induced obesity mouse model in relation to the host–microbial nutritional adaptation. PMID:24906017

Spontaneous parity violation and SUSY strong gauge theory

NASA Astrophysics Data System (ADS)

Haba, Naoyuki; Ohki, Hiroshi

2012-07-01

We suggest simple models of spontaneous parity violation in supersymmetric strong gauge theory. We focus on left-right symmetric model and investigate vacuum with spontaneous parity violation. Non-perturbative effects are calculable in supersymmetric gauge theory, and we suggest new models. Our models show confinement, so that we try to understand them by using a dual description of the theory. The left-right symmetry breaking and electroweak symmetry breaking are simultaneously occurred with the suitable energy scale hierarchy. This structure has several advantages compared to the MSSM. The scale of the Higgs mass (left-right breaking scale) and that of VEVs are different, so the SUSY little hierarchy problems are absent. The second model also induces spontaneous supersymmetry breaking [1].

Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation

PubMed Central

Raisch, Jennifer; Buc, Emmanuel; Bonnet, Mathilde; Sauvanet, Pierre; Vazeille, Emilie; de Vallée, Amélie; Déchelotte, Pierre; Darcha, Claude; Pezet, Denis; Bonnet, Richard; Bringer, Marie-Agnès; Darfeuille-Michaud, Arlette

2014-01-01

AIM: To provide further insight into the characterization of mucosa-associated Escherichia coli (E. coli) isolated from the colonic mucosa of cancer patients. METHODS: Phylogroups and the presence of cyclomodulin-encoding genes of mucosa-associated E. coli from colon cancer and diverticulosis specimens were determined by PCR. Adhesion and invasion experiments were performed with I-407 intestinal epithelial cells using gentamicin protection assay. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) expression in T84 intestinal epithelial cells was measured by enzyme-linked immunosorbent assay and by Western Blot. Gut colonization, inflammation and pro-carcinogenic potential were assessed in a chronic infection model using CEABAC10 transgenic mice. Cell proliferation was analyzed by real-time mRNA quantification of PCNA and immunohistochemistry staining of Ki67. RESULTS: Analysis of mucosa-associated E. coli from colon cancer and diverticulosis specimens showed that whatever the origin of the E. coli strains, 86% of cyclomodulin-positive E. coli belonged to B2 phylogroup and most harbored polyketide synthase (pks) island, which encodes colibactin, and/or cytotoxic necrotizing factor (cnf) genes. In vitro assays using I-407 intestinal epithelial cells revealed that mucosa-associated B2 E. coli strains were poorly adherent and invasive. However, mucosa-associated B2 E. coli similarly to Crohn’s disease-associated E. coli are able to induce CEACAM6 expression in T84 intestinal epithelial cells. In addition, in vivo experiments using a chronic infection model of CEACAM6 expressing mice showed that B2 E. coli strain 11G5 isolated from colon cancer is able to highly persist in the gut, and to induce colon inflammation, epithelial damages and cell proliferation. CONCLUSION: In conclusion, these data bring new insights into the ability of E. coli isolated from patients with colon cancer to establish persistent colonization, exacerbate inflammation and

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology

PubMed Central

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days −30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella, and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus, on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to

The Effects of Weaning Methods on Gut Microbiota Composition and Horse Physiology.

PubMed

Mach, Núria; Foury, Aline; Kittelmann, Sandra; Reigner, Fabrice; Moroldo, Marco; Ballester, Maria; Esquerré, Diane; Rivière, Julie; Sallé, Guillaume; Gérard, Philippe; Moisan, Marie-Pierre; Lansade, Léa

2017-01-01

Weaning has been described as one of the most stressful events in the life of horses. Given the importance of the interaction between the gut-brain axis and gut microbiota under stress, we evaluated (i) the effect of two different weaning methods on the composition of gut microbiota across time and (ii) how the shifts of gut microbiota composition after weaning affect the host. A total of 34 foals were randomly subjected to a progressive (P) or an abrupt (A) weaning method. In the P method, mares were separated from foals at progressively increasing intervals every day, starting from five min during the fourth week prior to weaning and ending with 6 h during the last week before weaning. In the A method, mares and foals were never separated prior to weaning (0 d). Different host phenotypes and gut microbiota composition were studied across 6 age strata (days -30, 0, 3, 5, 7, and 30 after weaning) by 16S rRNA gene sequencing. Results revealed that the beneficial species belonging to Prevotella, Paraprevotella , and Ruminococcus were more abundant in the A group prior to weaning compared to the P group, suggesting that the gut microbiota in the A cohort was better adapted to weaning. Streptococcus , on the other hand, showed the opposite pattern after weaning. Fungal loads, which are thought to increase the capacity for fermenting the complex polysaccharides from diet, were higher in P relative to A. Beyond the effects of weaning methods, maternal separation at weaning markedly shifted the composition of the gut microbiota in all foals, which fell into three distinct community types at 3 days post-weaning. Most genera in community type 2 (i.e., Eubacterium, Coprococcus, Clostridium XI, and Blautia spp.) were negatively correlated with salivary cortisol levels, but positively correlated with telomere length and N-butyrate production. Average daily gain was also greater in the foals harboring a community type 2 microbiota. Therefore, community type 2 is likely to

Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice.

PubMed

Allen, Jacob M; Berg Miller, Margret E; Pence, Brandt D; Whitlock, Keith; Nehra, Vandana; Gaskins, H Rex; White, Bryan A; Fryer, John D; Woods, Jeffrey A

2015-04-15

We have previously shown that voluntary wheel running (VWR) attenuates, whereas forced treadmill running (FTR) exacerbates, intestinal inflammation and clinical outcomes in a mouse model of colitis. As the gut microbiome is implicated in colitis, we hypothesized that VWR and FTR would differentially affect the gut microbiome. Mice (9-10/treatment) were randomly assigned to VWR, FTR, or sedentary home cage control (SED) for 6 wk. VWR were given running wheel access, whereas FTR ran on a treadmill for 40 min/day at 8-12 m/min, 5% grade. Forty-eight hours after the last exercise session, DNA was isolated from the fecal pellets and cecal contents, and the conserved bacterial 16S rRNA gene was amplified and sequenced using the Illumina Miseq platform. Permutational multivariate analysis of variance based on weighted UniFrac distance matrix revealed different bacterial clusters between feces and cecal contents in all groups (P < 0.01). Interestingly, the community structures of the three treatment groups clustered separately from each other in both gut regions (P < 0.05). Contrary to our hypothesis, the α-diversity metric, Chao1, indicated that VWR led to reduced bacterial richness compared with FTR or SED (P < 0.05). Taxonomic evaluation revealed that both VWR and FTR altered many individual bacterial taxa. Of particular interest, Turicibacter spp., which has been strongly associated with immune function and bowel disease, was significantly lower in VWR vs. SED/FTR. These data indicate that VWR and FTR differentially alter the intestinal microbiome of mice. These effects were observed in both the feces and cecum despite vastly different community structures between each intestinal region. Copyright © 2015 the American Physiological Society.

Mind-altering with the gut: Modulation of the gut-brain axis with probiotics.

PubMed

Kim, Namhee; Yun, Misun; Oh, Young Joon; Choi, Hak-Jong

2018-03-01

It is increasingly evident that bidirectional interactions exist among the gastrointestinal tract, the enteric nervous system, and the central nervous system. Recent preclinical and clinical trials have shown that gut microbiota plays an important role in these gut-brain interactions. Furthermore, alterations in gut microbiota composition may be associated with pathogenesis of various neurological disorders, including stress, autism, depression, Parkinson's disease, and Alzheimer's disease. Therefore, the concepts of the microbiota-gut-brain axis is emerging. Here, we review the role of gut microbiota in bidirectional interactions between the gut and the brain, including neural, immune-mediated, and metabolic mechanisms. We highlight recent advances in the understanding of probiotic modulation of neurological and neuropsychiatric disorders via the gut-brain axis.

Papillomavirus E6 oncoproteins

PubMed Central

Vande Pol, Scott B.; Klingelhutz, Aloysius J.

2013-01-01

Papillomaviruses induce benign and malignant epithelial tumors, and the viral E6 oncoprotein is essential for full transformation. E6 contributes to transformation by associating with cellular proteins, docking on specific acidic LXXLL peptide motifs found on the associated cellular proteins. This review examines insights from recent studies of human and animal E6 proteins that determine the three-dimensional structure of E6 when bound to acidic LXXLL peptides. The structure of E6 is related to recent advances in the purification and identification of E6 associated protein complexes. These E6 protein-complexes, together with other proteins that bind to E6, alter a broad array of biological outcomes including modulation of cell survival, cellular transcription, host cell differentiation, growth factor dependence, DNA damage responses, and cell cycle progression. PMID:23711382

The human gut resistome

PubMed Central

van Schaik, Willem

2015-01-01

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota (‘the gut resistome’). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium. PMID:25918444

The human gut resistome.

PubMed

van Schaik, Willem

2015-06-05

In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota ('the gut resistome'). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium.

Gut content analysis of Lake Michigan waterbirds in years with avian botulism type E mortality, 2010–2012

USGS Publications Warehouse

Essian, David A.; Chipault, Jennifer G.; Lafrancois, Brenda M.; Leonard, Jill B.K.

2016-01-01

Waterbird die-offs caused by Clostridium botulinum neurotoxin type E (BoNT/E) have occurred sporadically in the Great Lakes since the late 1960s, with a recent pulse starting in the late 1990s. In recent die-offs, round gobies (Neogobius melanostomus) have been implicated as vectors for the transfer of BoNT/E to fish-eating birds due to the round goby invasion history and their importance as prey. Dreissenid mussels (Dreissena spp.) are also potentially involved in BoNT/E transmission to birds and round gobies. We examined gut contents of waterbirds collected in Lake Michigan during die-offs in 2010–2012, and the gut contents of culled, presumably BoNT/E-free double-crested cormorants (Phalacrocorax auritus). Round gobies were found in 86% of the BoNT/E-positive individuals, 84% of the BoNT/E-negative birds, and 94% of the BoNT/E-free cormorants examined. Double-crested cormorants, ring-billed gulls (Larus delewarensis), and common loons (Gavia immer) consumed larger-sized round gobies than horned and red-necked grebes (Podiceps auritus and Podiceps grisegena), white-winged scoters (Melanitta deglandi), and long-tailed ducks (Clangula hymealis). Other common prey included dreissenid mussels, terrestrial insects, and alewives (Alosa pseudoharengus). Our data emphasize the importance of round gobies and mussels in diets of Lake Michigan waterbirds and suggest they may play a role in the transfer of BoNT/E to waterbirds; however, round gobies and mussels were found in BoNT/E-positive, -negative, and -free individuals, suggesting that other factors, such as alternative trophic pathways for toxin transfer, bird migratory timing and feeding locations, prey behavior, and individual physiological differences across birds may affect the likelihood that a bird will succumb to BoNT/E intoxication.

Association of papillomavirus E6 proteins with either MAML1 or E6AP clusters E6 proteins by structure, function, and evolutionary relatedness

PubMed Central

Brimer, Nicole

2017-01-01

Papillomavirus E6 proteins bind to LXXLL peptide motifs displayed on targeted cellular proteins. Alpha genus HPV E6 proteins associate with the cellular ubiquitin ligase E6AP (UBE3A), by binding to an LXXLL peptide (ELTLQELLGEE) displayed by E6AP, thereby stimulating E6AP ubiquitin ligase activity. Beta, Gamma, and Delta genera E6 proteins bind a similar LXXLL peptide (WMSDLDDLLGS) on the cellular transcriptional co-activator MAML1 and thereby repress Notch signaling. We expressed 45 different animal and human E6 proteins from diverse papillomavirus genera to ascertain the overall preference of E6 proteins for E6AP or MAML1. E6 proteins from all HPV genera except Alpha preferentially interacted with MAML1 over E6AP. Among animal papillomaviruses, E6 proteins from certain ungulate (SsPV1 from pigs) and cetacean (porpoises and dolphins) hosts functionally resembled Alpha genus HPV by binding and targeting the degradation of E6AP. Beta genus HPV E6 proteins functionally clustered with Delta, Pi, Tau, Gamma, Chi, Mu, Lambda, Iota, Dyokappa, Rho, and Dyolambda E6 proteins to bind and repress MAML1. None of the tested E6 proteins physically and functionally interacted with both MAML1 and E6AP, indicating an evolutionary split. Further, interaction of an E6 protein was insufficient to activate degradation of E6AP, indicating that E6 proteins that target E6AP co-evolved to separately acquire both binding and triggering of ubiquitin ligase activation. E6 proteins with similar biological function clustered together in phylogenetic trees and shared structural features. This suggests that the divergence of E6 proteins from either MAML1 or E6AP binding preference is a major event in papillomavirus evolution. PMID:29281732

The prebiotics 3′Sialyllactose and 6′Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: evidence for effects on the gut-brain axis

PubMed Central

Tarr, Andrew J.; Galley, Jeffrey D.; Fisher, Sydney; Chichlowski, Maciej; Berg, Brian M.; Bailey, Michael T.

2015-01-01

There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3′Sialyllactose (3′SL) or 6′Sialyllactose (6′SL) for two weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa-associated microbiota in control mice, as indicated by changes in beta diversity. The stressor resulted in anxiety-like behavior in both the light/dark preference and open field tests in control mice. This effect was associated with a reduction in immature neurons in the dentate gyrus as indicated by doublecortin (DCX) immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3′SL or 6′SL. In addition, 3′SL and 6′SL helped maintain normal behavior on tests of anxiety-like behavior and normal numbers of DCX+ immature neurons. These studies indicate that milk oligosaccharides support normal microbial communities and behavioral responses during stressor exposure, potentially through effects on the gut microbiota-brain axis. PMID:26144888

The severity of NAFLD is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota

PubMed Central

Boursier, Jérôme; Mueller, Olaf; Barret, Matthieu; Machado, Mariana; Fizanne, Lionel; Araujo-Perez, Felix; Guy, Cynthia D.; Seed, Patrick C.; Rawls, John F.; David, Lawrence A.; Hunault, Gilles; Oberti, Frédéric; Calès, Paul; Diehl, Anna Mae

2016-01-01

Background & aims Several animal studies have emphasized the role of gut microbiota in non-alcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remains scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, i.e. non-alcoholic steatohepatitis (NASH) and fibrosis, in a well-characterized population of adult NAFLD. Methods 57 patients with biopsy-proven NAFLD were enrolled. The taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Results 30 patients had F0/1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these 2 bacteria generated 3 patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, KEGG pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism. Conclusion NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre/probiotics therapies. PMID:26600078

TCDD influences reservoir of antibiotic resistance genes in murine gut microbiome.

PubMed

Stedtfeld, Robert D; Stedtfeld, Tiffany M; Fader, Kelly A; Williams, Maggie R; Bhaduri, Prianca; Quensen, John; Zacharewski, Timothy R; Tiedje, James M; Hashsham, Syed A

2017-05-01

Dysbiosis of the gut microbiome via antibiotics, changes in diet and infection can select for bacterial groups that more frequently harbor antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs). However, the impact of environmental toxicants on the reservoir of ARGs in the gut microbiome has received less attention. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist with multiple toxic health effects including immune dysfunction. The selective pressure of TCDD on the abundance of ARG and MGE-harboring gut populations was examined using C57BL/6 mice exposed to 0-30 μg/kg TCDD for 28 and 92 days with the latter having a 30-day recovery period. DNA extracted from temporally collected fecal pellets was characterized using a qPCR array with 384 assays targeting ARGs and MGEs. Fourteen genes, typically observed in Enterobacteriaceae, increased significantly within 8 days of initial dosing, persisted throughout the treatment period, and remained induced 30 days post dosing. A qPCR primer set targeting Enterobacteriaceae also showed 10- to 100-fold higher abundance in TCDD-treated groups, which was further verified using metagenomics. Results show a bloom of ARG-harboring bacterial groups in the gut due to a xenobiotic compound that is not a metal, biocide or antimicrobial. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Early-life gut microbiome and egg allergy.

PubMed

Fazlollahi, M; Chun, Y; Grishin, A; Wood, R A; Burks, A W; Dawson, P; Jones, S M; Leung, D Y M; Sampson, H A; Sicherer, S H; Bunyavanich, S

2018-07-01

Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10 -4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis P adj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10 -4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Carrageenan-induced colitis is associated with decreased population of anti-inflammatory bacterium, Akkermansia muciniphila, in the gut microbiota of C57BL/6J mice.

PubMed

Shang, Qingsen; Sun, Weixia; Shan, Xindi; Jiang, Hao; Cai, Chao; Hao, Jiejie; Li, Guoyun; Yu, Guangli

2017-09-05

Carrageenan as a food additive has been used for years. However, controversy exists regarding to the safety of carrageenan and accumulating evidence indicates that it could induce colitis in experimental models. Here, to provide more information on this issue and solve the debate, we studied and compared in detail the toxic effects of different isomers of carrageenan (κ-, ι-, and λ-) on the colon of C57BL/6J mice. Interestingly, all isomers of carrageenan were found to induce colitis with a comparable activity. Given that carrageenan is unabsorbed after oral administration, and also in light of the fact that gut microbiota plays a pivotal role in the pathogenesis of colitis, we further investigated the effect of carrageenan on gut microbiota using high-throughput sequencing. Intriguingly, carrageenan-induced colitis was observed to be robustly correlated with changes in the composition of gut microbiota. Specifically, all carrageenans significantly decreased the abundance of a potent anti-inflammatory bacterium, Akkermansia muciniphila, in the gut, which is highly relevant for understanding the toxic effect of carrageenan. Altogether, our results corroborate previous studies demonstrating harmful gastrointestinal effect of carrageenan and, from a gut microbiota perspective, shed new light into the mechanism by which carrageenan induces colitis in experimental animals. Copyright © 2017 Elsevier B.V. All rights reserved.

SUSY, the Third Generation and the LHC

NASA Astrophysics Data System (ADS)

Brust, Christopher; Katz, Andrey; Lawrence, Scott; Sundrum, Raman

2012-03-01

We develop a bottom-up approach to studying SUSY with light stops and sbottoms, but with other squarks and sleptons heavy and beyond reach of the LHC. We discuss the range of squark, gaugino and Higgsino masses for which the electroweak scale is radiatively stable over the "little hierarchy" below 10TeV. We review and expand on indirect constraints on this scenario, in particular from flavor and CP tests. We emphasize that in this context, R-parity violation is very well motivated. The phenomenological differences between Majorana and Dirac gauginos are also discussed. Finally, we focus on the light subsystem of stops, sbottom and neutralino with R-parity, in order to probe the current collider bounds. We find that 1/fb LHC bounds are mild and large parts of the motivated parameter space remain open, while the 10/fb data can be much more decisive.

The super-GUT CMSSM revisited

DOE PAGES

Ellis, John; Evans, Jason L.; Mustafayev, Azar; ...

2016-10-28

Here, we revisit minimal supersymmetric SU(5) grand unification (GUT) models in which the soft supersymmetry-breaking parameters of the minimal supersymmetric Standard Model (MSSM) are universal at some input scale, M in, above the supersymmetric gauge-coupling unification scale, M GUT. As in the constrained MSSM (CMSSM), we assume that the scalar masses and gaugino masses have common values, m 0 and m 1/2, respectively, at M in, as do the trilinear soft supersymmetry-breaking parameters A 0. Going beyond previous studies of such a super-GUT CMSSM scenario, we explore the constraints imposed by the lower limit on the proton lifetime and themore » LHC measurement of the Higgs mass, m h. We find regions of m 0, m 1/2 A 0 and the parameters of the SU(5) superpotential that are compatible with these and other phenomenological constraints such as the density of cold dark matter, which we assume to be provided by the lightest neutralino. Typically, these allowed regions appear for m 0 and m 1/2 in the multi-TeV region, for suitable values of the unknown SU(5) GUT-scale phases and superpotential couplings, and with the ratio of supersymmetric Higgs vacuum expectation values tan β≲6.« less

Tail gut cyst.

PubMed

Rao, G Mallikarjuna; Haricharan, P; Ramanujacharyulu, S; Reddy, K Lakshmi

2002-01-01

The tail gut is a blind extension of the hindgut into the tail fold just distal to the cloacal membrane. Remnants of this structure may form tail gut cyst. We report a 14-year-old girl with tail gut cyst that presented as acute abdomen. The patient recovered after cyst excision.

Is the Gut Microbiota a New Factor Contributing to Obesity and Its Metabolic Disorders?

PubMed Central

Harris, Kristina; Kassis, Amira; Major, Geneviève; Chou, Chieh J.

2012-01-01

The gut microbiota refers to the trillions of microorganisms residing in the intestine and is integral in multiple physiological processes of the host. Recent research has shown that gut bacteria play a role in metabolic disorders such as obesity, diabetes, and cardiovascular diseases. The mechanisms by which the gut microbiota affects metabolic diseases are by two major routes: (1) the innate immune response to the structural components of bacteria (e.g., lipopolysaccharide) resulting in inflammation and (2) bacterial metabolites of dietary compounds (e.g., SCFA from fiber), which have biological activities that regulate host functions. Gut microbiota has evolved with humans as a mutualistic partner, but dysbiosis in a form of altered gut metagenome and collected microbial activities, in combination with classic genetic and environmental factors, may promote the development of metabolic disorders. This paper reviews the available literature about the gut microbiota and aforementioned metabolic disorders and reveals the gaps in knowledge for future study. PMID:22315672

Beyond gut feelings: how the gut microbiota regulates blood pressure.

PubMed

Marques, Francine Z; Mackay, Charles R; Kaye, David M

2018-01-01

Hypertension is the leading risk factor for heart disease and stroke, and is estimated to cause 9.4 million deaths globally every year. The pathogenesis of hypertension is complex, but lifestyle factors such as diet are important contributors to the disease. High dietary intake of fruit and vegetables is associated with reduced blood pressure and lower cardiovascular mortality. A critical relationship between dietary intake and the composition of the gut microbiota has been described in the literature, and a growing body of evidence supports the role of the gut microbiota in the regulation of blood pressure. In this Review, we describe the mechanisms by which the gut microbiota and its metabolites, including short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides, act on downstream cellular targets to prevent or contribute to the pathogenesis of hypertension. These effects have a direct influence on tissues such as the kidney, the endothelium, and the heart. Finally, we consider the role of the gut microbiota in resistant hypertension, the possible intergenerational effect of the gut microbiota on blood pressure regulation, and the promising therapeutic potential of gut microbiota modification to improve health and prevent disease.

Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

PubMed

Bindels, Laure B; Neyrinck, Audrey M; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G; Langella, Philippe; Cani, Patrice D; Thissen, Jean-Paul; Delzenne, Nathalie M

2018-04-06

Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium ( Faecalibacterium prausnitzii ) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis.

Increased gut permeability in cancer cachexia: mechanisms and clinical relevance

PubMed Central

Bindels, Laure B.; Neyrinck, Audrey M.; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G.; Langella, Philippe; Cani, Patrice D.; Thissen, Jean-Paul; Delzenne, Nathalie M.

2018-01-01

Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium (Faecalibacterium prausnitzii) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis. PMID:29719601

Black Raspberries and Their Anthocyanin and Fiber Fractions Alter the Composition and Diversity of Gut Microbiota in F-344 Rats.

PubMed

Pan, Pan; Lam, Vy; Salzman, Nita; Huang, Yi-Wen; Yu, Jianhua; Zhang, Jianying; Wang, Li-Shu

2017-01-01

Natural compounds can alter the diversity and composition of the gut microbiome, potentially benefiting our health. We previously demonstrated chemopreventive effects of black raspberries (BRBs) in colorectal cancer, which is associated with gut dysbiosis. To investigate the effects of whole BRBs and their fractions on gut microbiota, we fed F-344 rats a control diet, 5% BRBs, the BRB anthocyanin fraction, or the BRB residue fraction for 6 weeks. Feces were collected at baseline and at weeks 3 and 6, and bacterial sequence counts were analyzed. We observed distinct patterns of microbiota from different diet groups. Beta diversity analysis suggested that all diet groups exerted time-dependent changes in the bacterial diversity. Hierarchical clustering analysis revealed that post-diet fecal microbiota was segregated from baseline fecal microbiota within each diet. It is interesting to note that fractions of BRBs induced different changes in gut bacteria compared to whole BRBs. The abundance of specific microbial species known to have anti-inflammatory effects, such as Akkermansia and Desulfovibrio, was increased by whole BRBs and their residue. Further, butyrate-producing bacteria, e.g., Anaerostipes, were increased by whole BRBs. Our results suggest that whole BRBs and their fractions alter the gut microbiota in ways that could significantly influence human health.

Why do larval helminths avoid the gut of intermediate hosts?

PubMed

Parker, G A; Ball, M A; Chubb, J C

2009-10-07

In complex life cycles, larval helminths typically migrate from the gut to exploit the tissues of their intermediate hosts. Yet the definitive host's gut is overwhelmingly the most favoured site for adult helminths to release eggs. Vertebrate nematodes with one-host cycles commonly migrate to a site in the host away from the gut before returning to the gut for reproduction; those with complex cycles occupy sites exclusively in the intermediate host's tissues or body spaces, and may or may not show tissue migration before (typically) returning to the gut in the definitive host. We develop models to explain the patterns of exploitation of different host sites, and in particular why larval helminths avoid the intermediate host's gut, and adult helminths favour it. Our models include the survival costs of migration between sites, and maximise fitness (=expected lifetime number of eggs produced by a given helminth propagule) in seeking the optimal strategy (host gut versus host tissue exploitation) under different growth, mortality, transmission and reproductive rates in the gut and tissues (i.e. sites away from the gut). We consider the relative merits of the gut and tissues, and conclude that (i) growth rates are likely to be higher in the tissues, (ii) mortality rates possibly higher in the gut (despite the immunological inertness of the gut lumen), and (iii) that there are very high benefits to egg release in the gut. The models show that these growth and mortality relativities would account for the common life history pattern of avoidance of the intermediate host's gut because the tissues offer a higher growth rate/mortality rate ratio (discounted by the costs of migration), and make a number of testable predictions. Though nematode larvae in paratenic hosts usually migrate to the tissues, unlike larvae in intermediates, they sometimes remain in the gut, which is predicted since in paratenics mortality rate and migration costs alone determine the site to be

The Role of the Gut Microbiota in Childhood Obesity.

PubMed

Pihl, Andreas Friis; Fonvig, Cilius Esmann; Stjernholm, Theresa; Hansen, Torben; Pedersen, Oluf; Holm, Jens-Christian

2016-08-01

Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism associated with obesity. We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism. The review discusses the potential role of the bacterial component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood obesity. A vast number of variables are influencing the gut microbial ecology (e.g., the host genetics, delivery method, diet, age, environment, and the use of pre-, pro-, and antibiotics); but the exact physiological processes behind these relationships need to be clarified. Exploring the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment.

Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity

PubMed Central

Vinderola, Gabriel; Matar, Chantal; Perdigón, Gabriela

2007-01-01

Background Fermented milks containing probiotic bacteria are a way of delivering bioactive constituents to targets in the gastrointestinal tract. We reported previously that the fermentation of milk at constant pH 6 by L. helveticus R389 increased its content of peptide fractions, and the oral administration of the non-bacterial fraction (FMSpH6) to mice increased total secretory IgA in the intestinal lumen and enhanced the number of IgA and various cytokines producing cells as well as the secretion of IL-6 by small intestine epithelial cells. We also demonstrated that this FMSpH6 was effective for the prevention of Salmonella typhimurium infection in mice. In this work, we studied in mice the impact of the oral administration of the supernatant of milk fermented by L. helveticus R389 on the gut physiology by measuring parameters such as calcium channels and E-cadherin expression, the activation of the biological signal calcineurin and mast and goblet cells, as a way to determine some mechanisms involved in the immunomodulating effects of the milk fermentation products, observed in previous studies. We analyzed the impact of the supernatant of milk fermented by L. helveticus R389 at pH6-controlled on the expression of calcineurin and on the reinforcement of the ephitelial barrier, measuring parameters such as calcium channels and E-cadherin expression and in the reinforcement of the non-specific immunity determining mast cells and goblet cells associated to the gut. Results We observed an enhanced expression of TRPV6 channels in the duodenum, indicating an improved capacity for dietary Ca2+ uptake. We demonstrated an enhanced expression of calcineurin in the small intestine, able to upregulate immune parameters such as IL-2 and TNF production, with an increase in the number of these cytokines secreting cells. We determined an increase in the number of mucosal mast cells and goblet cells, which would mean an improved state of mucosal surveillance at sites of

Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity.

PubMed

Vinderola, Gabriel; Matar, Chantal; Perdigón, Gabriela

2007-09-07

Fermented milks containing probiotic bacteria are a way of delivering bioactive constituents to targets in the gastrointestinal tract. We reported previously that the fermentation of milk at constant pH 6 by L. helveticus R389 increased its content of peptide fractions, and the oral administration of the non-bacterial fraction (FMSpH6) to mice increased total secretory IgA in the intestinal lumen and enhanced the number of IgA and various cytokines producing cells as well as the secretion of IL-6 by small intestine epithelial cells. We also demonstrated that this FMSpH6 was effective for the prevention of Salmonella typhimurium infection in mice. In this work, we studied in mice the impact of the oral administration of the supernatant of milk fermented by L. helveticus R389 on the gut physiology by measuring parameters such as calcium channels and E-cadherin expression, the activation of the biological signal calcineurin and mast and goblet cells, as a way to determine some mechanisms involved in the immunomodulating effects of the milk fermentation products, observed in previous studies. We analyzed the impact of the supernatant of milk fermented by L. helveticus R389 at pH6-controlled on the expression of calcineurin and on the reinforcement of the ephitelial barrier, measuring parameters such as calcium channels and E-cadherin expression and in the reinforcement of the non-specific immunity determining mast cells and goblet cells associated to the gut. We observed an enhanced expression of TRPV6 channels in the duodenum, indicating an improved capacity for dietary Ca2+ uptake. We demonstrated an enhanced expression of calcineurin in the small intestine, able to upregulate immune parameters such as IL-2 and TNF production, with an increase in the number of these cytokines secreting cells. We determined an increase in the number of mucosal mast cells and goblet cells, which would mean an improved state of mucosal surveillance at sites of infection. The oral

EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration.

PubMed

Xiang, Jinyi; Bandura, Jennifer; Zhang, Peng; Jin, Yinhua; Reuter, Hanna; Edgar, Bruce A

2017-05-09

Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors. Mature ECs lack EGF receptors and are refractory to growth signalling. Genetic tests indicated that stress-dependent EGFR/MAPK promotes gut regeneration via a novel mechanism that operates independently of Insulin/Pi3K/TOR signalling, which is nevertheless required in nonstressed conditions. The E2f1 transcription factor is required for and sufficient to drive EC endoreplication, and Ras/Raf signalling upregulates E2f1 levels posttranscriptionally. We illustrate how distinct signalling mechanisms direct stress-dependent versus homeostatic regeneration, and highlight the importance of postmitotic cell growth in gut epithelial repair.

EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration

PubMed Central

Xiang, Jinyi; Bandura, Jennifer; Zhang, Peng; Jin, Yinhua; Reuter, Hanna; Edgar, Bruce A.

2017-01-01

Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors. Mature ECs lack EGF receptors and are refractory to growth signalling. Genetic tests indicated that stress-dependent EGFR/MAPK promotes gut regeneration via a novel mechanism that operates independently of Insulin/Pi3K/TOR signalling, which is nevertheless required in nonstressed conditions. The E2f1 transcription factor is required for and sufficient to drive EC endoreplication, and Ras/Raf signalling upregulates E2f1 levels posttranscriptionally. We illustrate how distinct signalling mechanisms direct stress-dependent versus homeostatic regeneration, and highlight the importance of postmitotic cell growth in gut epithelial repair. PMID:28485389

A human gut phage catalog correlates the gut phageome with type 2 diabetes.

PubMed

Ma, Yingfei; You, Xiaoyan; Mai, Guoqin; Tokuyasu, Taku; Liu, Chenli

2018-02-01

Substantial efforts have been made to link the gut bacterial community to many complex human diseases. Nevertheless, the gut phages are often neglected. In this study, we used multiple bioinformatic methods to catalog gut phages from whole-community metagenomic sequencing data of fecal samples collected from both type II diabetes (T2D) patients (n = 71) and normal Chinese adults (n = 74). The definition of phage operational taxonomic units (pOTUs) and identification of large phage scaffolds (n = 2567, ≥ 10 k) revealed a comprehensive human gut phageome with a substantial number of novel sequences encoding genes that were unrelated to those in known phages. Interestingly, we observed a significant increase in the number of gut phages in the T2D group and, in particular, identified 7 pOTUs specific to T2D. This finding was further validated in an independent dataset of 116 T2D and 109 control samples. Co-occurrence/exclusion analysis of the bacterial genera and pOTUs identified a complex core interaction between bacteria and phages in the human gut ecosystem, suggesting that the significant alterations of the gut phageome cannot be explained simply by co-variation with the altered bacterial hosts. Alterations in the gut bacterial community have been linked to the chronic disease T2D, but the role of gut phages therein is not well understood. This is the first study to identify a T2D-specific gut phageome, indicating the existence of other mechanisms that might govern the gut phageome in T2D patients. These findings suggest the importance of the phageome in T2D risk, which warrants further investigation.

Diet, gut microbiota and cognition.

PubMed

Proctor, Cicely; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-02-01

The consumption of a diet high in fat and sugar can lead to the development of obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease and cognitive decline. In the human gut, the trillions of harmless microorganisms harboured in the host's gastrointestinal tract are called the 'gut microbiota'. Consumption of a diet high in fat and sugar changes the healthy microbiota composition which leads to an imbalanced microbial population in the gut, a phenomenon known as "gut dysbiosis". It has been shown that certain types of gut microbiota are linked to the pathogenesis of obesity. In addition, long-term consumption of a high fat diet is associated with cognitive decline. It has recently been proposed that the gut microbiota is part of a mechanistic link between the consumption of a high fat diet and the impaired cognition of an individual, termed "microbiota-gut-brain axis". In this complex relationship between the gut, the brain and the gut microbiota, there are several types of gut microbiota and host mechanisms involved. Most of these mechanisms are still poorly understood. Therefore, this review comprehensively summarizes the current evidence from mainly in vivo (rodent and human) studies of the relationship between diet, gut microbiota and cognition. The possible mechanisms that the diet and the gut microbiota have on cognition are also presented and discussed.

The Role of E6 Spliced Isoforms (E6*) in Human Papillomavirus-Induced Carcinogenesis

PubMed Central

Olmedo-Nieva, Leslie; Muñoz-Bello, J. Omar; Contreras-Paredes, Adriana

2018-01-01

Persistent infections with High Risk Human Papillomaviruses (HR-HPVs) are the main cause of cervical cancer development. The E6 and E7 oncoproteins of HR-HPVs are derived from a polycistronic pre-mRNA transcribed from an HPV early promoter. Through alternative splicing, this pre-mRNA produces a variety of E6 spliced transcripts termed E6*. In pre-malignant lesions and HPV-related cancers, different E6/E6* transcriptional patterns have been found, although they have not been clearly associated to cancer development. Moreover, there is a controversy about the participation of E6* proteins in cancer progression. This review addresses the regulation of E6 splicing and the different functions that have been found for E6* proteins, as well as their possible role in HPV-induced carcinogenesis. PMID:29346309

Precision corrections to fine tuning in SUSY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buckley, Matthew R.; Monteux, Angelo; Shih, David

Requiring that the contributions of supersymmetric particles to the Higgs mass are not highly tuned places upper limits on the masses of superpartners — in particular the higgsino, stop, and gluino. We revisit the details of the tuning calculation and introduce a number of improvements, including RGE resummation, two-loop effects, a proper treatment of UV vs. IR masses, and threshold corrections. This improved calculation more accurately connects the tuning measure with the physical masses of the superpartners at LHC-accessible energies. After these refinements, the tuning bound on the stop is now also sensitive to the masses of the 1st andmore » 2nd generation squarks, which limits how far these can be decoupled in Effective SUSY scenarios. We find that, for a fixed level of tuning, our bounds can allow for heavier gluinos and stops than previously considered. Despite this, the natural region of supersymmetry is under pressure from the LHC constraints, with high messenger scales particularly disfavored.« less

Precision corrections to fine tuning in SUSY

DOE PAGES

Buckley, Matthew R.; Monteux, Angelo; Shih, David

2017-06-20

Requiring that the contributions of supersymmetric particles to the Higgs mass are not highly tuned places upper limits on the masses of superpartners — in particular the higgsino, stop, and gluino. We revisit the details of the tuning calculation and introduce a number of improvements, including RGE resummation, two-loop effects, a proper treatment of UV vs. IR masses, and threshold corrections. This improved calculation more accurately connects the tuning measure with the physical masses of the superpartners at LHC-accessible energies. After these refinements, the tuning bound on the stop is now also sensitive to the masses of the 1st andmore » 2nd generation squarks, which limits how far these can be decoupled in Effective SUSY scenarios. We find that, for a fixed level of tuning, our bounds can allow for heavier gluinos and stops than previously considered. Despite this, the natural region of supersymmetry is under pressure from the LHC constraints, with high messenger scales particularly disfavored.« less

Talking microbes: When gut bacteria interact with diet and host organs

PubMed Central

Everard, Amandine

2016-01-01

Obesity and diabetes have reached epidemic proportions. Evidence suggests that besides dietary habits and physical activity, other environmental factors, such as gut microbes, are recognized as additional partners implicated in the control of energy homeostasis. Studies on the human gut microbiota have shown that the general population can be stratified on the sole basis of three dominant bacteria (i.e., the concept of enterotypes), while some others have suggested categorizing the population according to their microbiome gene richness. Both aspects have been strengthened by recent studies investigating the impact of nutrients (e.g., dietary fibers, fat feeding) and dietary habits (i.e., vegans versus omnivores) of different populations. Using preclinical models, quite a few novel mechanisms have been proposed in these gut microbiota–host interactions, including the role of novel bacteria, the regulation of antimicrobial peptide production, the maintenance of the gut barrier function and intestinal innate immunity. In this review, we discuss several of the aforementioned aspects. Nonetheless, determining the overall mechanisms by which microbes dialogue with host cells will require further investigations before anticipating the development of next‐generation nutritional interventions using prebiotics, probiotics, synbiotics, or even specific nutrients for promoting health benefits. PMID:26178924

Temporal and long-term gut microbiota variation in allergic disease: A prospective study from infancy to school age.

PubMed

Simonyté Sjödin, Kotryna; Hammarström, Marie-Louise; Rydén, Patrik; Sjödin, Andreas; Hernell, Olle; Engstrand, Lars; West, Christina E

2018-05-22

Compositional changes of the early life gut microbiota have been implicated in IgE-associated allergic disease but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE-associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T-cell regulation, estimated as responses to polyclonal T-cell activation. Stool samples were collected from 93 children at 4, 6 and 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children and mononuclear cells were polyclonally activated. Levels of IL-10 and FOXP3 mRNA copies were determined using real-time quantitative reverse transcriptase-PCR. At 8 years of age 21 children were diagnosed with IgE-associated allergic disease and 90% displayed allergic comorbidity. Seventy-two children were non-allergic and non-sensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella and Coprococcus in allergic compared to non-allergic children from infancy to school age. The gut microbiota of the allergic 8-year-olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus and Lachnospira. In allergic 8-year-olds, Faecalibacterium correlated with IL-10 mRNA levels (r s =0.49 , P adj= 0.02) with the same trend for FOXP3 (r s =0.39 , P adj= 0.08). We identified both temporal and long-term variation in the differential abundance of specific bacterial genera in children developing IgE-associated allergic disease. Improved dietary interventions aiming at expanding immune-modulatory taxa could be studied for prevention of allergic disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Obesity: An overview of possible role(s) of gut hormones, lipid sensing and gut microbiota.

PubMed

Mishra, Alok Kumar; Dubey, Vinay; Ghosh, Asit Ranjan

2016-01-01

Obesity is one of the major challenges for public health in 21st century, with 1.9 billion people being considered as overweight and 600 million as obese. There are certain diseases such as type 2 diabetes, hypertension, cardiovascular disease, and several forms of cancer which were found to be associated with obesity. Therefore, understanding the key molecular mechanisms involved in the pathogenesis of obesity could be beneficial for the development of a therapeutic approach. Hormones such as ghrelin, glucagon like peptide 1 (GLP-1) peptide YY (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK) secreted by an endocrine organ gut, have an intense impact on energy balance and maintenance of homeostasis by inducing satiety and meal termination. Glucose and energy homeostasis are also affected by lipid sensing in which different organs respond in different ways. However, there is one common mechanism i.e. formation of esterified lipids (long chain fatty acyl CoAs) and the activation of protein kinase C δ (PKC δ) involved in all these organs. The possible role of gut microbiota and obesity has been addressed by several researchers in recent years, indicating the possible therapeutic approach toward the management of obesity by the introduction of an external living system such as a probiotic. The proposed mechanism behind this activity is attributed by metabolites produced by gut microbial organisms. Thus, this review summarizes the role of various physiological factors such as gut hormone and lipid sensing involved in various tissues and organ and most important by the role of gut microbiota in weight management. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of gut peptides in the gut-brain-axis of livestock

USDA-ARS?s Scientific Manuscript database

Gut peptides are small hormones produced within the gut that are involved in many biological processes including, but not limited to, appetite regulation, mucosal growth, and metabolism regulation. Some peptides, such as cholecystokinin (CCK) and xenin-25 may affect appetite by altering gut motilit...

In vitro organogenesis of gut-like structures from mouse embryonic stem cells.

PubMed

Kuwahara, M; Ogaeri, T; Matsuura, R; Kogo, H; Fujimoto, T; Torihashi, S

2004-04-01

Embryonic stem (ES) cells have pluripotency and give rise to many cell types and tissues, including representatives of all three germ layers in the embryo. We have reported previously that mouse ES cells formed contracting gut-like organs from embryoid bodies (EBs). These gut-like structures contracted spontaneously, and had large lumens surrounded by three layers, i.e. epithelium, lamina propria and muscularis. Ganglia were scattered along the periphery, and interstitial cells of Cajal (ICC) were distributed among the smooth muscle cells. In the present study, to determine whether they can be a model of gut organogenesis, we investigated the formation process of the gut-like structures in comparison with embryonic gut development. As a result, we found that the fundamental process of formation in vitro was similar to embryonic gut development in vivo. The result indicates that the gut-like structure is a useful tool not only for developmental study to determine the factors that induce gut organogenesis, but also for studies of enteric neurone and ICC development.

Gut Protozoa: Friends or Foes of the Human Gut Microbiota?

PubMed

Chabé, Magali; Lokmer, Ana; Ségurel, Laure

2017-12-01

The importance of the gut microbiota for human health has sparked a strong interest in the study of the factors that shape its composition and diversity. Despite the growing evidence suggesting that helminths and protozoa significantly interact with gut bacteria, gut microbiome studies remain mostly focused on prokaryotes and on populations living in industrialized countries that typically have a low parasite burden. We argue that protozoa, like helminths, represent an important factor to take into account when studying the gut microbiome, and that their presence - especially considering their long coevolutionary history with humans - may be beneficial. From this perspective, we examine the relationship between the protozoa and their hosts, as well as their relevance for public health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prebiotics and gut microbiota in chickens.

PubMed

Pourabedin, Mohsen; Zhao, Xin

2015-08-01

Prebiotics are non-digestible feed ingredients that are metabolized by specific members of intestinal microbiota and provide health benefits for the host. Fermentable oligosaccharides are best known prebiotics that have received increasing attention in poultry production. They act through diverse mechanisms, such as providing nutrients, preventing pathogen adhesion to host cells, interacting with host immune systems and affecting gut morphological structure, all presumably through modulation of intestinal microbiota. Currently, fructooligosaccharides, inulin and mannanoligosaccharides have shown promising results while other prebiotic candidates such as xylooligosaccharides are still at an early development stage. Despite a growing body of evidence reporting health benefits of prebiotics in chickens, very limited studies have been conducted to directly link health improvements to prebiotic-dependent changes in the gut microbiota. This article visits the current knowledge of the chicken gastrointestinal microbiota and reviews most recent publications related to the roles played by prebiotics in modulation of the gut microbiota and immune functions. Progress in this field will help us better understand how the gut microbiota contributes to poultry health and productivity, and support the development of new prebiotic products as an alternative to in-feed antibiotics. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The gut in trauma.

PubMed

Patel, Jayshil J; Rosenthal, Martin D; Miller, Keith R; Martindale, Robert G

2016-08-01

The purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut-brain connection in traumatic brain injury. Newer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS). To date, therapies to mitigate acute gut dysfunction have included enteral nutrition and immunonutrition; emerging therapies aimed to intestinal mucosal layer disruption, however, include protease inhibitors such as tranexamic acid, parenteral nutrition-supplemented bombesin, and hypothermia. Clinical trials to demonstrate benefit in humans are needed before widespread applications can be recommended. Despite resuscitation, gut dysfunction promotes distant organ injury. In addition, postresuscitation nosocomial and iatrogenic 'hits' exaggerate the immune response, contributing to MODS. This was a provocative concept, suggesting infectious and noninfectious causes of inflammation may trigger, heighten, and perpetuate an inflammatory response culminating in MODS and death. Emerging evidence suggests posttraumatic injury mechanisms, such as intestinal mucosal disruption and shifting of the gut microbiome to a pathobiome. In addition, traumatic brain injury activates the gut-brain axis and increases intestinal permeability.

Gut microbiota and obesity.

PubMed

Gérard, Philippe

2016-01-01

The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination

PubMed Central

Mortensen, Franziska; Schneider, Daniel; Barbic, Tanja; Sladewska-Marquardt, Anna; Kühnle, Simone; Marx, Andreas; Scheffner, Martin

2015-01-01

Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein. PMID:26216987

Effects of selective digestive decontamination (SDD) on the gut resistome.

PubMed

Buelow, Elena; Gonzalez, Teresita Bello; Versluis, Dennis; Oostdijk, Evelien A N; Ogilvie, Lesley A; van Mourik, Maaike S M; Oosterink, Els; van Passel, Mark W J; Smidt, Hauke; D'Andrea, Marco Maria; de Been, Mark; Jones, Brian V; Willems, Rob J L; Bonten, Marc J M; van Schaik, Willem

2014-08-01

Selective digestive decontamination (SDD) is an infection prevention measure for critically ill patients in intensive care units (ICUs) that aims to eradicate opportunistic pathogens from the oropharynx and intestines, while sparing the anaerobic flora, by the application of non-absorbable antibiotics. Selection for antibiotic-resistant bacteria is still a major concern for SDD. We therefore studied the impact of SDD on the reservoir of antibiotic resistance genes (i.e. the resistome) by culture-independent approaches. We evaluated the impact of SDD on the gut microbiota and resistome in a single ICU patient during and after an ICU stay by several metagenomic approaches. We also determined by quantitative PCR the relative abundance of two common aminoglycoside resistance genes in longitudinally collected samples from 12 additional ICU patients who received SDD. The patient microbiota was highly dynamic during the hospital stay. The abundance of antibiotic resistance genes more than doubled during SDD use, mainly due to a 6.7-fold increase in aminoglycoside resistance genes, in particular aph(2″)-Ib and an aadE-like gene. We show that aph(2″)-Ib is harboured by anaerobic gut commensals and is associated with mobile genetic elements. In longitudinal samples of 12 ICU patients, the dynamics of these two genes ranged from a ∼10(4) fold increase to a ∼10(-10) fold decrease in relative abundance during SDD. ICU hospitalization and the simultaneous application of SDD has large, but highly individualized, effects on the gut resistome of ICU patients. Selection for transferable antibiotic resistance genes in anaerobic commensal bacteria could impact the risk of transfer of antibiotic resistance genes to opportunistic pathogens. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular details of a starch utilization pathway in the human gut symbiont Eubacterium rectale

PubMed Central

Cockburn, Darrell W.; Orlovsky, Nicole I.; Foley, Matthew H.; Kwiatkowski, Kurt J.; Bahr, Constance M.; Maynard, Mallory; Demeler, Borries; Koropatkin, Nicole M.

2015-01-01

Summary Eubacterium rectale is a prominent human gut symbiont yet little is known about the molecular strategies this bacterium has developed to acquire nutrients within the competitive gut ecosystem. Starch is one of the most abundant glycans in the human diet, and E. rectale increases in vivo when the host consumes a diet rich in resistant starch, although it is not a primary degrader of this glycan. Here we present the results of a quantitative proteomics study in which we identify two glycoside hydrolase 13 family enzymes, and three ABC transporter solute-binding proteins that are abundant during growth on starch and, we hypothesize, work together at the cell surface to degrade starch and capture the released maltooligosaccharides. EUR_21100 is a multidomain cell wall anchored amylase that preferentially targets starch polysaccharides, liberating maltotetraose, while the membrane associated maltogenic amylase EUR_01860 breaks down maltooligosaccharides longer than maltotriose. The three solute-binding proteins display a range of glycan-binding specificities that ensure the capture of glucose through maltoheptaose and some α1,6-branched glycans. Taken together, we describe a pathway for starch utilization by E. rectale DSM 17629 that may be conserved among other starch-degrading Clostridium cluster XIVa organisms in the human gut. PMID:25388295

Supersymmetry searches in GUT models with non-universal scalar masses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cannoni, M.; Gómez, M.E.; Ellis, J.

2016-03-01

We study SO(10), SU(5) and flipped SU(5) GUT models with non-universal soft supersymmetry-breaking scalar masses, exploring how they are constrained by LHC supersymmetry searches and cold dark matter experiments, and how they can be probed and distinguished in future experiments. We find characteristic differences between the various GUT scenarios, particularly in the coannihilation region, which is very sensitive to changes of parameters. For example, the flipped SU(5) GUT predicts the possibility of ∼t{sub 1}−χ coannihilation, which is absent in the regions of the SO(10) and SU(5) GUT parameter spaces that we study. We use the relic density predictions in differentmore » models to determine upper bounds for the neutralino masses, and we find large differences between different GUT models in the sparticle spectra for the same LSP mass, leading to direct connections of distinctive possible experimental measurements with the structure of the GUT group. We find that future LHC searches for generic missing E{sub T}, charginos and stops will be able to constrain the different GUT models in complementary ways, as will the Xenon 1 ton and Darwin dark matter scattering experiments and future FERMI or CTA γ-ray searches.« less

Microbes vs. chemistry in the origin of the anaerobic gut lumen.

PubMed

Friedman, Elliot S; Bittinger, Kyle; Esipova, Tatiana V; Hou, Likai; Chau, Lillian; Jiang, Jack; Mesaros, Clementina; Lund, Peder J; Liang, Xue; FitzGerald, Garret A; Goulian, Mark; Lee, Daeyeon; Garcia, Benjamin A; Blair, Ian A; Vinogradov, Sergei A; Wu, Gary D

2018-04-17

The succession from aerobic and facultative anaerobic bacteria to obligate anaerobes in the infant gut along with the differences between the compositions of the mucosally adherent vs. luminal microbiota suggests that the gut microbes consume oxygen, which diffuses into the lumen from the intestinal tissue, maintaining the lumen in a deeply anaerobic state. Remarkably, measurements of luminal oxygen levels show nearly identical pO 2 (partial pressure of oxygen) profiles in conventional and germ-free mice, pointing to the existence of oxygen consumption mechanisms other than microbial respiration. In vitro experiments confirmed that the luminal contents of germ-free mice are able to chemically consume oxygen (e.g., via lipid oxidation reactions), although at rates significantly lower than those observed in the case of conventionally housed mice. For conventional mice, we also show that the taxonomic composition of the gut microbiota adherent to the gut mucosa and in the lumen throughout the length of the gut correlates with oxygen levels. At the same time, an increase in the biomass of the gut microbiota provides an explanation for the reduction of luminal oxygen in the distal vs. proximal gut. These results demonstrate how oxygen from the mammalian host is used by the gut microbiota, while both the microbes and the oxidative chemical reactions regulate luminal oxygen levels, shaping the composition of the microbial community throughout different regions of the gut.

Natural little hierarchy for SUSY from radiative breaking of the Peccei-Quinn symmetry

NASA Astrophysics Data System (ADS)

Bae, Kyu Jung; Baer, Howard; Serce, Hasan

2015-01-01

While LHC8 Higgs mass and sparticle search constraints favor a multi-TeV value of soft SUSY breaking terms, electroweak naturalness favors a superpotential Higgsino mass μ ˜100 - 200 GeV : the mismatch results in an apparent little hierarchy characterized by μ ≪msoft (with msoft˜m3 /2 in gravity mediation). It has been suggested that the little hierarchy arises from a mismatch between Peccei-Quinn (PQ) and hidden sector intermediate scales vPQ≪mhidden . We examine the Murayama-Suzuki-Yanagida model of radiatively driven PQ symmetry breaking which not only generates a weak scale value of μ but also produces intermediate scale Majorana masses for right-hand neutrinos. For this model, we show ranges of parameter choices with multi-TeV values of m3 /2 which can easily generate values of μ ˜100 - 200 GeV so that the apparent little hierarchy suggested from data emerges quite naturally. In such a scenario, dark matter would be comprised of an axion plus a Higgsino-like weakly-interacting massive particle admixture where the axion mass and Higgsino masses are linked by the value of the PQ scale. The required light Higgsinos should ultimately be detected at a linear e+e- collider with √{s }>2 m (Higgsino) .

Composition of the gut microbiota modulates the severity of malaria

PubMed Central

Villarino, Nicolas F.; LeCleir, Gary R.; Denny, Joshua E.; Dearth, Stephen P.; Harding, Christopher L.; Sloan, Sarah S.; Gribble, Jennifer L.; Campagna, Shawn R.; Wilhelm, Steven W.; Schmidt, Nathan W.

2016-01-01

Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from “resistant” or “susceptible” mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden. PMID:26858424

A Multicentre Audit of Single-Use Surgical Instruments (SUSI) for Tonsillectomy and Adenoidectomy

PubMed Central

O'Flynn, P; Silva, S; Kothari, P; Persaud, R

2007-01-01

INTRODUCTION Prions are resistant to conventional sterilisation procedures and, therefore, could be transmitted iatrogenically through re-usable adenoid and tonsil surgical instruments. Using disposable instruments would avoid the risk of transmission. We present the results of a complete audit loop using BBraun single-use surgical instruments (SUSI). PATIENTS AND METHODS This was a prospective multicentre audit. Surgeons were asked to fill in a standardised questionnaire recording details including postoperative complications, and evaluation of each piece of equipment compared with their own experience of conventional re-usable instruments. In the first cycle, constructive criticisms of the instruments were noted and the manufacturers modified the instruments accordingly. A second cycle of audit was subsequently undertaken. RESULTS A total of 86 patients were audited in the first cycle and 97 in the second cycle. Postoperative haemorrhage rate for both cycles was well within acceptable range. In the first audit cycle, surgeons generally found the Draffin rods, Boyle-Davis gag and bipolar diathermy forceps of poor quality and difficult to use. These were redesigned and, on repeat evaluation during the second audit cycle, were found to be just as good, if not better, than the re-usable instruments. CONCLUSIONS This study suggests that SUSI may be just as good as re-usable instruments. Furthermore, they may be more cost effective. PMID:18201478

Diets Alter the Gut Microbiome of Crocodile Lizards

PubMed Central

Jiang, Hai-Ying; Ma, Jing-E; Li, Juan; Zhang, Xiu-Juan; Li, Lin-Miao; He, Nan; Liu, Hai-Yang; Luo, Shu-Yi; Wu, Zheng-Jun; Han, Ri-Chou; Chen, Jin-Ping

2017-01-01

The crocodile lizard is a critically endangered reptile, and serious diseases have been found in this species in recent years, especially in captive lizards. Whether these diseases are caused by changes in the gut microbiota and the effect of captivity on disease remains to be determined. Here, we examined the relationship between the gut microbiota and diet and disease by comparing the fecal microbiota of wild lizards with those of sick and healthy lizards in captivity. The gut microbiota in wild crocodile lizards was consistently dominated by Proteobacteria (∼56.4%) and Bacteroidetes (∼19.1%). However, the abundance of Firmicutes (∼2.6%) in the intestine of the wild crocodile lizards was distinctly lower than that in other vertebrates. In addition, the wild samples from Guangdong Luokeng Shinisaurus crocodilurus National Nature Reserve also had a high abundance of Deinococcus–Thermus while the wild samples from Guangxi Daguishan Crocodile Lizard National Nature Reserve had a high abundance of Tenericutes. The gut microbial community in loach-fed crocodile lizards was significantly different from the gut microbial community in the earthworm-fed and wild lizards. In addition, significant differences in specific bacteria were detected among groups. Notably, in the gut microbiota, the captive lizards fed earthworms resulted in enrichment of Fusobacterium, and the captive lizards fed loaches had higher abundances of Elizabethkingia, Halomonas, Morganella, and Salmonella, all of which are pathogens or opportunistic pathogens in human or other animals. However, there is no sufficient evidence that the gut microbiota contributes to either disease A or disease B. These results provide a reference for the conservation of endangered crocodile lizards and the first insight into the relationship between disease and the gut microbiota in lizards. PMID:29118742

Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla

PubMed Central

Mahowald, Michael A.; Rey, Federico E.; Seedorf, Henning; Turnbaugh, Peter J.; Fulton, Robert S.; Wollam, Aye; Shah, Neha; Wang, Chunyan; Magrini, Vincent; Wilson, Richard K.; Cantarel, Brandi L.; Coutinho, Pedro M.; Henrissat, Bernard; Crock, Lara W.; Russell, Alison; Verberkmoes, Nathan C.; Hettich, Robert L.; Gordon, Jeffrey I.

2009-01-01

The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial–microbial and microbial–host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability. PMID:19321416

Fit reduced GUTS models online: From theory to practice.

PubMed

Baudrot, Virgile; Veber, Philippe; Gence, Guillaume; Charles, Sandrine

2018-05-20

Mechanistic modeling approaches, such as the toxicokinetic-toxicodynamic (TKTD) framework, are promoted by international institutions such as the European Food Safety Authority and the Organization for Economic Cooperation and Development to assess the environmental risk of chemical products generated by human activities. TKTD models can encompass a large set of mechanisms describing the kinetics of compounds inside organisms (e.g., uptake and elimination) and their effect at the level of individuals (e.g., damage accrual, recovery, and death mechanism). Compared to classical dose-response models, TKTD approaches have many advantages, including accounting for temporal aspects of exposure and toxicity, considering data points all along the experiment and not only at the end, and making predictions for untested situations as realistic exposure scenarios. Among TKTD models, the general unified threshold model of survival (GUTS) is within the most recent and innovative framework but is still underused in practice, especially by risk assessors, because specialist programming and statistical skills are necessary to run it. Making GUTS models easier to use through a new module freely available from the web platform MOSAIC (standing for MOdeling and StAtistical tools for ecotoxIClogy) should promote GUTS operability in support of the daily work of environmental risk assessors. This paper presents the main features of MOSAIC_GUTS: uploading of the experimental data, GUTS fitting analysis, and LCx estimates with their uncertainty. These features will be exemplified from literature data. Integr Environ Assess Manag 2018;00:000-000. © 2018 SETAC. © 2018 SETAC.

The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis.

PubMed

Freedman, Samantha N; Shahi, Shailesh K; Mangalam, Ashutosh K

2018-01-01

Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.

Gut microbiome and bone.

PubMed

Ibáñez, Lidia; Rouleau, Matthieu; Wakkach, Abdelilah; Blin-Wakkach, Claudine

2018-04-11

The gut microbiome is now viewed as a tissue that interacts bidirectionally with the gastrointestinal, immune, endocrine and nervous systems, affecting the cellular responses in numerous organs. Evidence is accumulating of gut microbiome involvement in a growing number of pathophysiological processes, many of which are linked to inflammatory responses. More specifically, data acquired over the last decade point to effects of the gut microbiome on bone mass regulation and on the development of bone diseases (such as osteoporosis) and of inflammatory joint diseases characterized by bone loss. Mice lacking a gut microbiome have bone mass alteration that can be reversed by gut recolonization. Changes in the gut microbiome composition have been reported in mice with estrogen-deficiency osteoporosis and have also been found in a few studies in humans. Probiotic therapy decreases bone loss in estrogen-deficient animals. The effect of the gut microbiome on bone tissue involves complex mechanisms including modulation of CD4 + T cell activation, control of osteoclastogenic cytokine production and modifications in hormone levels. This complexity may contribute to explain the discrepancies observed betwwen some studies whose results vary depending on the age, gender, genetic background and treatment duration. Further elucidation of the mechanisms involved is needed. However, the available data hold promise that gut microbiome manipulation may prove of interest in the management of bone diseases. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Deciphering chicken gut microbial dynamics based on high-throughput 16S rRNA metagenomics analyses.

PubMed

Mohd Shaufi, Mohd Asrore; Sieo, Chin Chin; Chong, Chun Wie; Gan, Han Ming; Ho, Yin Wan

2015-01-01

Chicken gut microbiota has paramount roles in host performance, health and immunity. Understanding the topological difference in gut microbial community composition is crucial to provide knowledge on the functions of each members of microbiota to the physiological maintenance of the host. The gut microbiota profiling of the chicken was commonly performed previously using culture-dependent and early culture-independent methods which had limited coverage and accuracy. Advances in technology based on next-generation sequencing (NGS), offers unparalleled coverage and depth in determining microbial gut dynamics. Thus, the aim of this study was to investigate the ileal and caecal microbiota development as chicken aged, which is important for future effective gut modulation. Ileal and caecal contents of broiler chicken were extracted from 7, 14, 21 and 42-day old chicken. Genomic DNA was then extracted and amplified based on V3 hyper-variable region of 16S rRNA. Bioinformatics, ecological and statistical analyses such as Principal Coordinate Analysis (PCoA) was performed in mothur software and plotted using PRIMER 6. Additional analyses for predicted metagenomes were performed through PICRUSt and STAMP software package based on Greengenes databases. A distinctive difference in bacterial communities was observed between ilea and caeca as the chicken aged (P < 0.001). The microbial communities in the caeca were more diverse in comparison to the ilea communities. The potentially pathogenic bacteria such as Clostridium were elevated as the chicken aged and the population of beneficial microbe such as Lactobacillus was low at all intervals. On the other hand, based on predicted metagenomes analysed, clear distinction in functions and roles of gut microbiota such as gene pathways related to nutrient absorption (e.g. sugar and amino acid metabolism), and bacterial proliferation and colonization (e.g. bacterial motility proteins, two-component system and bacterial secretion

Comparative gut physiology symposium: The microbe-gut-brain axis

USDA-ARS?s Scientific Manuscript database

The Comparative Gut Physiology Symposium titled “The Microbe-Gut-Brain Axis” was held at the Joint Annual Meeting of the American Society of Animal Science and the American Dairy Science Association on Thursday, July 21, 2016, in Salt Lake City Utah. The goal of the symposium was to present basic r...

Gut Microbiota and Extreme Longevity.

PubMed

Biagi, Elena; Franceschi, Claudio; Rampelli, Simone; Severgnini, Marco; Ostan, Rita; Turroni, Silvia; Consolandi, Clarissa; Quercia, Sara; Scurti, Maria; Monti, Daniela; Capri, Miriam; Brigidi, Patrizia; Candela, Marco

2016-06-06

The study of the extreme limits of human lifespan may allow a better understanding of how human beings can escape, delay, or survive the most frequent age-related causes of morbidity, a peculiarity shown by long-living individuals. Longevity is a complex trait in which genetics, environment, and stochasticity concur to determine the chance to reach 100 or more years of age [1]. Because of its impact on human metabolism and immunology, the gut microbiome has been proposed as a possible determinant of healthy aging [2, 3]. Indeed, the preservation of host-microbes homeostasis can counteract inflammaging [4], intestinal permeability [5], and decline in bone and cognitive health [6, 7]. Aiming at deepening our knowledge on the relationship between the gut microbiota and a long-living host, we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarians, thus reconstructing the longest available human microbiota trajectory along aging. We highlighted the presence of a core microbiota of highly occurring, symbiotic bacterial taxa (mostly belonging to the dominant Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families), with a cumulative abundance decreasing along with age. Aging is characterized by an increasing abundance of subdominant species, as well as a rearrangement in their co-occurrence network. These features are maintained in longevity and extreme longevity, but peculiarities emerged, especially in semi-supercentenarians, describing changes that, even accommodating opportunistic and allochthonous bacteria, might possibly support health maintenance during aging, such as an enrichment and/or higher prevalence of health-associated groups (e.g., Akkermansia, Bifidobacterium, and Christensenellaceae). Copyright © 2016 Elsevier Ltd. All rights reserved.

Importance of the gut-brain axis in the control of glucose homeostasis.

PubMed

Migrenne, Stéphanie; Marsollier, Nicolas; Cruciani-Guglielmacci, Céline; Magnan, Christophe

2006-12-01

Adult mammals finely match glucose production to glucose utilization, thus allowing glycaemia to be maintained in a physiological range of 0.8-1.2mg/dl whatever the energetic status of the mammal (i.e. fed or fasted, rested or exercised). To accomplish this, peripheral signals originating from the gut 'inform' the central nervous system, which in turn is able to monitor the status of both peripheral glucose stores and ongoing fuel availability. Indeed, both secretion and action of hormones regulating endogenous glucose production and utilization are regulated by the autonomic nervous system. These gut signals are either hormonal (e.g. glucagon-like peptide-1, ghrelin and cholecystokinine) or neuronal (e.g. afferent vagus nerve fibres). Recent data, combined with the development of incretin analogues for treatment of diabetes, highlight the importance of the gut-brain axis, especially glucagon-like peptide-1 and ghrelin, in the control of glucose homeostasis.

Handling stress may confound murine gut microbiota studies.

PubMed

Allen-Blevins, Cary R; You, Xiaomeng; Hinde, Katie; Sela, David A

2017-01-01

Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis) , a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantis during critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis , we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium , Bacteroides , Bacteroidetes, and Firmicutes. Our results

Gut microbiota and metabolic syndrome.

PubMed

Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

2014-11-21

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

Factors influencing the grass carp gut microbiome and its effect on metabolism.

PubMed

Ni, Jiajia; Yan, Qingyun; Yu, Yuhe; Zhang, Tanglin

2014-03-01

Gut microbiota have attracted extensive attention recently because of their important role in host metabolism, immunity and health maintenance. The present study focused on factors affecting the gut microbiome of grass carp (Ctenopharyngodon idella) and further explored the potential effect of the gut microbiome on metabolism. Totally, 43.39 Gb of screened metagenomic sequences obtained from 24 gut samples were fully analysed. We detected 1228 phylotypes (116 Archaea and 1112 Bacteria), most of which belonged to the phyla Firmicutes, Proteobacteria and Fusobacteria. Totally, 41335 of the detected open reading frames (ORFs) were matched to Kyoto Encyclopedia of Genes and Genomes pathways, and carbohydrate and amino acid metabolism was the main matched pathway deduced from the annotated ORFs. Redundancy analysis based on the phylogenetic composition and gene composition of the gut microbiome indicated that gut fullness and feeding (i.e. ryegrass vs. commercial feed, and pond-cultured vs. wild) were significantly related to the gut microbiome. Moreover, many biosynthesis and metabolism pathways of carbohydrates, amino acids and lipids were significantly enhanced by the gut microbiome in ryegrass-fed grass carp. These findings suggest that the metabolic role played by the gut microbiome in grass carp can be affected by feeding. These findings contribute to the field of fish gut microbial ecology and also provide a basis for follow-up functional studies. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

PubMed Central

Kao, Wynn H.; Beaudenon, Sylvie L.; Talis, Andrea L.; Huibregtse, Jon M.; Howley, Peter M.

2000-01-01

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells. PMID:10864652

Genetic difference but functional similarity among fish gut bacterial communities through molecular and biochemical fingerprints.

PubMed

Mouchet, Maud A; Bouvier, Corinne; Bouvier, Thierry; Troussellier, Marc; Escalas, Arthur; Mouillot, David

2012-03-01

Considering the major involvement of gut microflora in the digestive function of various macro-organisms, bacterial communities inhabiting fish guts may be the main actors of organic matter degradation by fish. Nevertheless, the extent and the sources of variability in the degradation potential of gut bacterial communities are largely overlooked. Using Biolog Ecoplate™ and denaturing gradient gel electrophoresis (DGGE), we explored functional (i.e. the ability to degrade organic matter) and genetic (i.e. identification of DGGE banding patterns) diversity of fish gut bacterial communities, respectively. Gut bacterial communities were extracted from fish species characterized by different diets sampled along a salinity gradient in the Patos-Mirim lagoons complex (Brazil). We found that functional diversity was surprisingly unrelated to genetic diversity of gut bacterial communities. Functional diversity was not affected by the sampling site but by fish species and diet, whereas genetic diversity was significantly influenced by all three factors. Overall, the functional diversity was consistently high across fish individuals and species, suggesting a wide functional niche breadth and a high potential of organic matter degradation. We conclude that fish gut bacterial communities may strongly contribute to nutrient cycling regardless of their genetic diversity and environment. © European Union 2011.

Effect of probiotics on the meat flavour and gut microbiota of chicken.

PubMed

Wang, Yan; Sun, Jing; Zhong, Hang; Li, Nianzhen; Xu, Hengyong; Zhu, Qing; Liu, Yiping

2017-07-25

To date, no report has demonstrated the use of beneficial microbes for contributing to the flavour characteristics and gut microbiota diversity of chicken. Here, we selected six probiotics obtained from our laboratory and supplemented them in six different combinations to 420 newborn male Qingjiaoma chickens under the same controlled living environment (60 birds, no probiotic supplements). The results showed that chicken supplemented with Bacillus species showed beneficial effects in body weight. Acetate is the major fermentation production in the chicken caecum, and chicken supplemented with Pediococcus pentosaceus had the average higher short chain fatty acids (SCFAs) contents. In chicken caecal microflora, the abundance of Bacteroidetes bacteria was positively correlated with the content of propionate, butyrate, and isobutyrate, whereas an increase in acetate content was positively correlated to the abundance of Firmicutes. Compared to chickens without probiotic supplement, chickens supplemented with P. pentosaceus had more characteristic flavour compounds in the sampled breast meat, especially higher concentrations of (E)-2-heptenal, (E,E)-2,4-nonadienal, and certain C6-C9 unsaturated fatty acids. This resulted in a stronger chicken-fatty or fatty odour which directly improved the flavour. These findings suggest that probiotics can improve chicken meat flavour and increase gut microbiota diversity.

Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

PubMed

Allen, Jacob M; Mailing, Lucy J; Niemiro, Grace M; Moore, Rachel; Cook, Marc D; White, Bryan A; Holscher, Hannah D; Woods, Jeffrey A

2018-04-01

Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection. Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection. β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

Understanding the gut microbiome of dairy calves: Opportunities to improve early-life gut health.

PubMed

Malmuthuge, Nilusha; Guan, Le Luo

2017-07-01

Early gut microbiota plays a vital role in the long-term health of the host. However, understanding of these microbiota is very limited in livestock species, especially in dairy calves. Neonatal calves are highly susceptible to enteric infections, one of the major causes of calf death, so approaches to improving gut health and overall calf health are needed. An increasing number of studies are exploring the microbial composition of the gut, the mucosal immune system, and early dietary interventions to improve the health of dairy calves, revealing possibilities for effectively reducing the susceptibility of calves to enteric infections while promoting growth. Still, comprehensive understanding of the effect of dietary interventions on gut microbiota-one of the key aspects of gut health-is lacking. Such knowledge may provide in-depth understanding of the mechanisms behind functional changes in response to dietary interventions. Understanding of host-microbial interactions with dietary interventions and the role of the gut microbiota during pathogenesis at the site of infection in early life is vital for designing effective tools and techniques to improve calf gut health. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Gut microbiome and psyche: paradigm shift in the concept of brain-gut axis].

PubMed

Konturek, Peter C; Zopf, Yurdagül

2016-05-25

The concept of the brain-gut axis describes the communication between the central and enteric nervous system. The exchange of information takes place in both directions. The great advances in molecular medicine in recent years led to the discovery of an enormous number of microorganisms in the intestine (gut microbiome), which greatly affect the function of the brain-gut axis. Overview Numerous studies indicate that the dysfunction of the brain-gut axis could lead to both inflammatory and functional diseases of the gastrointestinal tract. Moreover, it was shown that a faulty composition of the gut microbiota in childhood influences the maturation of the central nervous system and thus may favor the development of mental disorders such as autism, depression, or other. An exact causal relationship between psyche and microbiome must be clarified by further studies in order to find new therapeutic options.

Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis

PubMed Central

Giannelli, Valerio; Di Gregorio, Vincenza; Iebba, Valerio; Giusto, Michela; Schippa, Serena; Merli, Manuela; Thalheimer, Ulrich

2014-01-01

Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called “gut-liver axis”, with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis. PMID:25492994

Protein- and RNA-Enhanced Fermentation by Gut Microbiota of the Earthworm Lumbricus terrestris.

PubMed

Zeibich, Lydia; Schmidt, Oliver; Drake, Harold L

2018-06-01

Earthworms are a dominant macrofauna in soil ecosystems and have determinative effects on soil fertility and plant growth. These invertebrates feed on ingested material, and gizzard-linked disruption of ingested fungal and bacterial cells is conceived to provide diverse biopolymers in the anoxic alimentary canals of earthworms. Fermentation in the gut is likely important to the utilization of ingested biopolymer-derived compounds by the earthworm. This study therefore examined the fermentative responses of gut content-associated microbes of the model earthworm Lumbricus terrestris to (i) microbial cell lysate (to simulate gizzard-disrupted cells) and (ii) dominant biopolymers of such biomass, protein, and RNA. The microbial cell lysate augmented the production of H 2 , CO 2 , and diverse fatty acids (e.g., formate, acetate, propionate, succinate, and butyrate) in anoxic gut content microcosms, indicating that the cell lysate triggered diverse fermentations. Protein and RNA also augmented diverse fermentations in anoxic microcosms of gut contents, each yielding a distinct product profile (e.g., RNA yielded H 2 and succinate, whereas protein did not). The combined product profile of protein and RNA treatments was similar to that of cell lysate treatments, and 16S rRNA-based analyses indicated that many taxa that responded to cell lysate were similar to taxa that responded to protein or RNA. In particular, protein stimulated Peptostreptococcaceae , Clostridiaceae , and Fusobacteriaceae , whereas RNA stimulated Aeromonadaceae These findings demonstrate the capacity of gut-associated obligate anaerobes and facultative aerobes to catalyze biopolymer-driven fermentations and highlight the potential importance of protein and RNA as substrates linked to the overall turnover dynamics of organic carbon in the alimentary canal of the earthworm. IMPORTANCE The subsurface lifestyle of earthworms makes them an unnoticed component of the terrestrial biosphere. However, the

Gut-Brain Axis and Behavior.

PubMed

Martin, Clair R; Mayer, Emeran A

2017-01-01

In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Gut microbiota and metabolic syndrome

PubMed Central

Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

2014-01-01

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal “superorganism” seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host’s immune system could culminate in the intestinal translocation of bacterial fragments and the development of “metabolic endotoxemia”, leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use. PMID:25473159

Carbohydrates and the human gut microbiota.

PubMed

Chassard, Christophe; Lacroix, Christophe

2013-07-01

Due to its scale and its important role in maintaining health, the gut microbiota can be considered as a 'new organ' inside the human body. Many complex carbohydrates are degraded and fermented by the human gut microbiota in the large intestine to both yield basic energy salvage and impact gut health through produced metabolites. This review will focus on the gut microbes and microbial mechanisms responsible for polysaccharides degradation and fermentation in the large intestine. Gut microbes and bacterial metabolites impact the host at many levels, including modulation of inflammation, and glucose and lipid metabolisms. A complex relationship occurs in the intestine between the human gut microbiota, diet and the host. Research on carbohydrates and gut microbiota composition and functionality is fast developing and will open opportunities for prevention and treatment of obesity, diabetes and other related metabolic disorders through manipulation of the gut ecosystem.

Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats.

PubMed

Zhang, Qian; Yu, Hongyue; Xiao, Xinhua; Hu, Ling; Xin, Fengjiao; Yu, Xiaobing

2018-01-01

Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck , G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3-V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae , Phascolarctobacterium , and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio , which produce lipopolysaccharide (LPS). The

Pathophysiology of the Gut and the Microbiome in the Host Response.

PubMed

Lyons, John D; Coopersmith, Craig M

2017-03-01

To describe and summarize the data supporting the gut as the motor driving critical illness and multiple organ dysfunction syndrome presented at the National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015). Summary of workshop keynote presentation. Not applicable. Presented by an expert in the field, the data assessing the role of gastrointestinal dysfunction driving critical illness were described with a focus on identifying knowledge gaps and research priorities. Summary of presentation and discussion supported and supplemented by relevant literature. The understanding of gut dysfunction in critical illness has evolved greatly over time, and the gut is now often considered as the "motor" of critical illness. The association of the gut with critical illness is supported by both animal models and clinical studies. Initially, the association between gut dysfunction and critical illness focused primarily on bacterial translocation into the bloodstream. However, that work has evolved to include other gut-derived products causing distant injury via other routes (e.g., lymphatics). Additionally, alterations in the gut epithelium may be associated with critical illness and influence outcomes. Gut epithelial apoptosis, intestinal hyperpermeability, and perturbations in the intestinal mucus layer have all been associated with critical illness. Finally, there is growing evidence that the intestinal microbiome plays a crucial role in mediating pathology in critical illness. Further research is needed to better understand the role of each of these mechanisms and their contribution to multiple organ dysfunction syndrome in children.

Sialidases from gut bacteria: a mini-review.

PubMed

Juge, Nathalie; Tailford, Louise; Owen, C David

2016-02-01

Sialidases are a large group of enzymes, the majority of which catalyses the cleavage of terminal sialic acids from complex carbohydrates on glycoproteins or glycolipids. In the gastrointestinal (GI) tract, sialic acid residues are mostly found in terminal location of mucins via α2-3/6 glycosidic linkages. Many enteric commensal and pathogenic bacteria can utilize sialic acids as a nutrient source, but not all express the sialidases that are required to release free sialic acid. Sialidases encoded by gut bacteria vary in terms of their substrate specificity and their enzymatic reaction. Most are hydrolytic sialidases, which release free sialic acid from sialylated substrates. However, there are also examples with transglycosylation activities. Recently, a third class of sialidases, intramolecular trans-sialidase (IT-sialidase), has been discovered in gut microbiota, releasing (2,7-anhydro-Neu5Ac) 2,7-anydro-N-acetylneuraminic acid instead of sialic acid. Reaction specificity varies, with hydrolytic sialidases demonstrating broad activity against α2,3-, α2,6- and α2,8-linked substrates, whereas IT-sialidases tend to be specific for α2,3-linked substrates. In this mini-review, we summarize the current knowledge on the structural and biochemical properties of sialidases involved in the interaction between gut bacteria and epithelial surfaces. © 2016 Authors.

Changes in human gut flora with age: an Indian familial study.

PubMed

Marathe, Nachiket; Shetty, Sudarshan; Lanjekar, Vikram; Ranade, Dilip; Shouche, Yogesh

2012-09-26

The gut micro flora plays vital role in health status of the host. The majority of microbes residing in the gut have a profound influence on human physiology and nutrition. Different human ethnic groups vary in genetic makeup as well as the environmental conditions they live in. The gut flora changes with genetic makeup and environmental factors and hence it is necessary to understand the composition of gut flora of different ethnic groups. Indian population is different in physiology from western population (YY paradox) and thus the gut flora in Indian population is likely to differ from the extensively studied gut flora in western population. In this study we have investigated the gut flora of two Indian families, each with three individuals belonging to successive generations and living under the same roof. Denaturation gradient gel electrophoresis analysis showed age-dependant variation in gut microflora amongst the individuals within a family. Different bacterial genera were dominant in the individual of varying age in clone library analysis. Obligate anaerobes isolated from individuals within a family showed age related differences in isolation pattern, with 27% (6 out of 22) of the isolates being potential novel species based on 16S rRNA gene sequence. In qPCR a consistent decrease in Firmicutes number and increase in Bacteroidetes number with increasing age was observed in our subjects, this pattern of change in Firmicutes / Bacteroidetes ratio with age is different than previously reported in European population. There is change in gut flora with age amongst the individuals within a family. The isolation of high percent of novel bacterial species and the pattern of change in Firmicutes /Bacteroidetes ratio with age suggests that the composition of gut flora in Indian individuals may be different than the western population. Thus, further extensive study is needed to define the gut flora in Indian population.

CoMiniGut—a small volume in vitro colon model for the screening of gut microbial fermentation processes

PubMed Central

Khakimov, Bekzod; Nielsen, Sebastian; Sørensen, Helena; van den Berg, Frans; Nielsen, Dennis Sandris

2018-01-01

Driven by the growing recognition of the influence of the gut microbiota (GM) on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v). We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs) were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative abundance of

Small Bowel Transit and Altered Gut Microbiota in Patients With Liver Cirrhosis.

PubMed

Liu, Yang; Jin, Ye; Li, Jun; Zhao, Lei; Li, Zhengtian; Xu, Jun; Zhao, Fuya; Feng, Jing; Chen, Huinan; Fang, Chengyuan; Shilpakar, Rojina; Wei, Yunwei

2018-01-01

Disturbance of the gut microbiota is common in liver cirrhosis (LC) patients, the underlying mechanisms of which are yet to be unfolded. This study aims to explore the relationship between small bowel transit (SBT) and gut microbiota in LC patients. Cross-sectional design was applied with 36 LC patients and 20 healthy controls (HCs). The gut microbiota was characterized by 16S rRNA gene sequencing. The Firmicutes/Bacteroidetes (F/B) ratio and the Microbial Dysbiosis index (MDI) were used to evaluate the severity of microbiota dysbiosis. The scintigraphy method was performed in patients to describe the objective values of SBT. Patients were then subdivided according to the Child-Pugh score (threshold = 5) or SBT value (threshold = 0.6) for microbiota analysis. LC patients were characterized by an altered gut microbiota; F/B ratios and MDI were higher than HC in both Child_5 (14.00 ± 14.69 vs. 2.86 ± 0.99, p < 0.01; 0.49 ± 0.80 vs. -0.47 ± 0.69, p < 0.01) and Child_5+ (15.81 ± 15.11 vs. 2.86±0.99, p < 0.01; 1.11 ± 1.05 vs. -0.47 ± 0.69, p < 0.01) sub-groups in patients. Difference in the gut microbiota between Child_ 5 and Child_5+ patients was inappreciable, but the SBT was relatively slower in Child_5+ patients (43 ± 26% vs. 80 ± 15%, p < 0.05). Compared with the Child-Pugh score indicators, SBT showed stronger associations with bacterial genera. A clear difference in the gut microbiota was observed between SBT_0.6- and SBT_0.6+ patients [Pr(> F ) = 0.0068, pMANOVA], with higher F/B ratios and MDI in SBT_0.6- patients (19.71 ± 16.62 vs. 7.33 ± 6.65, p < 0.01; 1.02 ± 0.97 vs. 0.20 ± 0.58, p < 0.01). Similar results were observed between the SBT_0.6- and SBT_0.6+ sub-groups of patients with normal liver function and a Child-Pugh score of 5. SBT was negatively correlated with both the F/B ratio and MDI ( r = -0.34, p < 0.05; r = -0.38, p < 0.05). Interestingly, an increased capacity for the inferred pathway "bacterial invasion of epithelial cells" in

Gut microbiota trajectory in patients with severe burn: A time series study.

PubMed

Wang, Xinying; Yang, Jianbo; Tian, Feng; Zhang, Li; Lei, Qiucheng; Jiang, Tingting; Zhou, Jihong; Yuan, Siming; Wang, Jun; Feng, Zhijian; Li, Jieshou

2017-12-01

This time series experiments aimed to investigate the dynamic change of gut microbiomes after severe burn and its association with enteral nutrition (EN). Seven severely burned patients who suffered from a severe metal dust explosion injury were recruited in this study. The dynamic changes of gut microbiome of fecal samples at six time points (1-3days, 2, 3, 4, 5 and 6weeks after severe burn) were detected using 16S ribosomal RNA pyrosequencing technology. Following the post-burn temporal order, gut microbiota dysbiosis was detected in the gut microbiome after severe burn, then it was gradually resolved. The bio-diversity of gut bacteria was initially decreased, and then returned to normal level. In addition, at the early stage (from 2 to 4weeks), the majority of those patients' gut microbiome were opportunistic pathogen genus, Enterococcus and Escherichia; while at the end of this study, the majority was a beneficial genus, Bacteroides. EN can promote the recovery of gut microbiota, especially in EN well-tolerated patients. Severe burn injury can cause a dramatic dysbiosis of gut microbiota. A trend of enriched beneficial bacteria and diminished opportunistic pathogen bacteria may serve as prognosis microbiome biomarkers of severe burn patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Control of lupus nephritis by changes of gut microbiota.

PubMed

Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R; Ahmed, S Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E; Branson, David B; Kirby, Jay L; Goswami, Poorna; Leeth, Caroline M; Read, Kaitlin A; Oestreich, Kenneth J; Vieson, Miranda D; Reilly, Christopher M; Luo, Xin M

2017-07-11

Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.

Diminution of the gut resistome after a gut microbiota-targeted dietary intervention in obese children

PubMed Central

Wu, Guojun; Zhang, Chenhong; Wang, Jing; Zhang, Feng; Wang, Ruirui; Shen, Jian; Wang, Linghua; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping; Zhang, Menghui

2016-01-01

The gut microbiome represents an important reservoir of antibiotic resistance genes (ARGs). Effective methods are urgently needed for managing the gut resistome to fight against the antibiotic resistance threat. In this study, we show that a gut microbiota-targeted dietary intervention, which shifts the dominant fermentation of gut bacteria from protein to carbohydrate, significantly diminished the gut resistome and alleviated metabolic syndrome in obese children. Of the non-redundant metagenomic gene catalog of ~2 × 106 microbial genes, 399 ARGs were identified in 131 gene types and conferred resistance to 47 antibiotics. Both the richness and diversity of the gut resistome were significantly reduced after the intervention. A total of 201 of the 399 ARGs were carried in 120 co-abundance gene groups (CAGs) directly binned from the gene catalog across both pre-and post-intervention samples. The intervention significantly reduced several CAGs in Klebsiella, Enterobacter and Escherichia, which were the major hubs for multiple resistance gene types. Thus, dietary intervention may become a potentially effective method for diminishing the gut resistome. PMID:27044409

Fatty liver accompanies an increase in lactobacillus species in the hind gut of C57BL/6 mice fed a high-fat diet.

PubMed

Zeng, Huawei; Liu, Jun; Jackson, Matthew I; Zhao, Feng-Qi; Yan, Lin; Combs, Gerald F

2013-05-01

High-fat (HF) diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease and changes in the gut microbiome. To test the hypothesis that HF feeding increases certain predominant hind gut bacteria and development of steatohepatitis, C57BL/6 mice were fed an HF (45% energy) or low-fat (LF) (10% energy) diet for 10 wk. At the end of the feeding period, body weights in the HF group were 34% greater than those in the LF group (P < 0.05). These changes were associated with dramatic increases in lipid droplet number and size, inflammatory cell infiltration, and inducible nitric oxide (NO) synthase protein concentration in the livers of mice fed the HF diet. Consistent with the fatty liver phenotype, plasma leptin and tumor necrosis factor-α concentrations were also elevated in mice fed the HF diet, indicative of chronic inflammation. Eight of 12 pairs of polymerase chain reaction (PCR) primers for bacterial species that typically predominate hind gut microbial ecology generated specific PCR products from the fecal DNA samples. The amount of DNA from Lactobacillus gasseri and/or Lactobacillus taiwanensis in the HF group was 6900-fold greater than that in the LF group. Many of these bacteria are bile acid resistant and are capable of bile acid deconjugation. Because bile acids are regulators of hepatic lipid metabolism, the marked increase of gut L. gasseri and/or L. taiwanensis species bacteria with HF feeding may play a role in development of steatohepatitis in this model.

Gut microbiota and allogeneic transplantation.

PubMed

Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

2015-08-23

The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

Engineering bacterial thiosulfate and tetrathionate sensors for detecting gut inflammation.

PubMed

Daeffler, Kristina N-M; Galley, Jeffrey D; Sheth, Ravi U; Ortiz-Velez, Laura C; Bibb, Christopher O; Shroyer, Noah F; Britton, Robert A; Tabor, Jeffrey J

2017-04-03

There is a groundswell of interest in using genetically engineered sensor bacteria to study gut microbiota pathways, and diagnose or treat associated diseases. Here, we computationally identify the first biological thiosulfate sensor and an improved tetrathionate sensor, both two-component systems from marine Shewanella species, and validate them in laboratory Escherichia coli Then, we port these sensors into a gut-adapted probiotic E. coli strain, and develop a method based upon oral gavage and flow cytometry of colon and fecal samples to demonstrate that colon inflammation (colitis) activates the thiosulfate sensor in mice harboring native gut microbiota. Our thiosulfate sensor may have applications in bacterial diagnostics or therapeutics. Finally, our approach can be replicated for a wide range of bacterial sensors and should thus enable a new class of minimally invasive studies of gut microbiota pathways. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia.

PubMed

Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

2016-04-01

Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

C33-A cells transfected with E6*I or E6*II the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis.

PubMed

Vaisman, Carolina E; Del Moral-Hernandez, Oscar; Moreno-Campuzano, Samadhi; Aréchaga-Ocampo, Elena; Bonilla-Moreno, Raul; Garcia-Aguiar, Israel; Cedillo-Barron, Leticia; Berumen, Jaime; Nava, Porfirio; Villegas-Sepúlveda, Nicolas

2018-03-02

The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the unspliced HPV-16 E6/E7 pre-mRNA product and 3 alternatively spliced mRNAs. The 3 spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and E6^E7. In this study we showed that transfection of C-33A cells with monocistronic constructs of these cDNAs fused to GFP, produced different effects on apoptosis, after the treatment with cisplatin. Transfection of C-33A cells with the full-length E6-GFP oncoprotein resulted in a 50% decrease in cell death, while the transfection with the E6*I-GFP construct showed only a 25% of diminution of cell death, compared to the control cells. Transfection with the E6^E7-GFP or E7-GFP construct had no effect on the number of the apoptotic cells, compared with control cells. Conversely, transfection with the E6*II construct resulted in higher cell death than the control cells. Taken together, these results suggested that E6*I or E6*II, the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis, when transfected in C-33A cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Gut-liver axis: gut microbiota in shaping hepatic innate immunity.

PubMed

Wu, Xunyao; Tian, Zhigang

2017-11-01

Gut microbiota play an essential role in shaping immune cell responses. The liver was continuously exposed to metabolic products of intestinal commensal bacterial through portal vein and alteration of gut commensal bateria was always associated with increased risk of liver inflammation and autoimmune disease. Considered as a unique immunological organ, the liver is enriched with a large number of innate immune cells. Herein, we summarize the available literature of gut microbiota in shaping the response of hepatic innate immune cells including NKT cells, NK cells, γδ T cells and Kupffer cells during health and disease. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of innate immune cell-related liver disease.

Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

PubMed

Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

2016-09-01

The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

The gut microenvironment of sediment-dwelling Chironomus plumosus larvae as characterised with O2, pH, and redox microsensors.

PubMed

Stief, Peter; Eller, Gundula

2006-09-01

We devised a set-up in which microsensors can be used for characterising the gut microenvironment of aquatic macrofauna. In a small flow cell, we measured microscale gradients through dissected guts (O(2), pH, redox potential [E ( h )]), in the haemolymph (O(2)), and towards the body surface (O(2)) of Chironomus plumosus larvae. The gut microenvironment was compared with the chemical conditions in the lake sediment in which the animals reside and feed. When the dissected guts were incubated at the same nominal O(2) concentration as in haemolymph, the gut content was completely anoxic and had pH and E ( h ) values slightly lower than in the ambient sediment. When the dissected guts were artificially oxygenated, the volumetric O(2)-consumption rates of the gut content were at least 10x higher than in the sediment. Using these potential O(2)-consumption rates in a cylindrical diffusion-reaction model, it was predicted that diffusion of O(2) from the haemolymph to the gut could not oxygenate the gut content under in vivo conditions. Additionally, the potential O(2)-consumption rates were so high that the intake of dissolved O(2) along with feeding could be ruled out to oxygenate the gut content. We conclude that microorganisms present in the gut of C. plumosus cannot exhibit an aerobic metabolism. The presented microsensor technique and the data analysis are applicable to guts of other macrofauna species with cutaneous respiration.

Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88.

PubMed

Larsson, Erik; Tremaroli, Valentina; Lee, Ying Shiuan; Koren, Omry; Nookaew, Intawat; Fricker, Ashwana; Nielsen, Jens; Ley, Ruth E; Bäckhed, Fredrik

2012-08-01

The gut microbiota has profound effects on host physiology but local host-microbial interactions in the gut are only poorly characterised and are likely to vary from the sparsely colonised duodenum to the densely colonised colon. Microorganisms are recognised by pattern recognition receptors such as Toll-like receptors, which signal through the adaptor molecule MyD88. To identify host responses induced by gut microbiota along the length of the gut and whether these required MyD88, transcriptional profiles of duodenum, jejunum, ileum and colon were compared from germ-free and conventionally raised wild-type and Myd88-/- mice. The gut microbial ecology was assessed by 454-based pyrosequencing and viruses were analysed by PCR. The gut microbiota modulated the expression of a large set of genes in the small intestine and fewer genes in the colon but surprisingly few microbiota-regulated genes required MyD88 signalling. However, MyD88 was essential for microbiota-induced colonic expression of the antimicrobial genes Reg3β and Reg3γ in the epithelium, and Myd88 deficiency was associated with both a shift in bacterial diversity and a greater proportion of segmented filamentous bacteria in the small intestine. In addition, conventionally raised Myd88-/- mice had increased expression of antiviral genes in the colon, which correlated with norovirus infection in the colonic epithelium. This study provides a detailed description of tissue-specific host transcriptional responses to the normal gut microbiota along the length of the gut and demonstrates that the absence of MyD88 alters gut microbial ecology.

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia

PubMed Central

Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom

2016-01-01

Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections. PMID:26511795

The Green Gut: Chlorophyll Degradation in the Gut of Spodoptera littoralis.

PubMed

Badgaa, Amarsanaa; Büchler, Rita; Wielsch, Natalie; Walde, Marie; Heintzmann, Rainer; Pauchet, Yannik; Svatos, Ales; Ploss, Kerstin; Boland, Wilhelm

2015-11-01

Chlorophylls, the most prominent natural pigments, are part of the daily diet of herbivorous insects. The spectrum of ingested and digested chlorophyll metabolites compares well to the pattern of early chlorophyll-degradation products in senescent plants. Intact chlorophyll is rapidly degraded by proteins in the front- and midgut. Unlike plants, insects convert both chlorophyll a and b into the corresponding catabolites. MALDI-TOF/MS imaging allowed monitoring the distribution of the chlorophyll catabolites along the gut of Spodoptera littoralis larvae. The chlorophyll degradation in the fore- and mid-gut is strongly pH dependent, and requires alkaline conditions. Using LC-MS/MS analysis we identified a lipocalin-type protein in the intestinal fluid of S. littoralis homolog to the chlorophyllide a binding protein from Bombyx mori. Widefield and high-resolution autofluorescence microscopy revealed that the brush border membranes are covered with the chlorophyllide binding protein tightly bound via its GPI-anchor to the gut membrane. A function in defense against gut microbes is discussed.

CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis

PubMed Central

Stromberg, Paul E.; Woolsey, Cheryl A.; Clark, Andrew T.; Clark, Jessica A.; Turnbull, Isaiah R.; McConnell, Kevin W.; Chang, Katherine C.; Chung, Chun-Shiang; Ayala, Alfred; Buchman, Timothy G.; Hotchkiss, Richard S.; Coopersmith, Craig M.

2009-01-01

Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1−/− and wild-type (WT) mice. However, Rag-1−/− animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1−/− mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4+ but not CD8+, γδ, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1−/− mice. Further, adoptively transferring lymphocytes to Rag-1−/− mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4+ lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality.—Stromberg, P. E., Woolsey, C. A., Clark, A. T., Clark, J. A., Turnbull, I. R., McConnell, K. W., Chang, K. C., Chung, C.-S., Ayala, A., Buchman, T. G., Hotchkiss, R. S., Coopersmith, C. M. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis. PMID:19158156

The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease.

PubMed

Yang, Tao; Richards, Elaine M; Pepine, Carl J; Raizada, Mohan K

2018-07-01

Crosstalk between the gut microbiota and the host has attracted considerable attention owing to its involvement in diverse diseases. Chronic kidney disease (CKD) is commonly associated with hypertension and is characterized by immune dysregulation, metabolic disorder and sympathetic activation, which are all linked to gut dysbiosis and altered host-microbiota crosstalk. In this Review, we discuss the complex interplay between the brain, the gut, the microbiota and the kidney in CKD and hypertension and explain our brain-gut-kidney axis hypothesis for the pathogenesis of these diseases. Consideration of the role of the brain-gut-kidney axis in the maintenance of normal homeostasis and of dysregulation of this axis in CKD and hypertension could lead to the identification of novel therapeutic targets. In addition, the discovery of unique microbial communities and their associated metabolites and the elucidation of brain-gut-kidney signalling are likely to fill fundamental knowledge gaps leading to innovative research, clinical trials and treatments for CKD and hypertension.

Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota.

PubMed

Bauer, Paige V; Hamr, Sophie C; Duca, Frank A

2016-02-01

Despite significant progress in understanding the homeostatic regulation of energy balance, successful therapeutic options for curbing obesity remain elusive. One potential target for the treatment of obesity is via manipulation of the gut-brain axis, a complex bidirectional communication system that is crucial in maintaining energy homeostasis. Indeed, ingested nutrients induce secretion of gut peptides that act either via paracrine signaling through vagal and non-vagal neuronal relays, or in an endocrine fashion via entry into circulation, to ultimately signal to the central nervous system where appropriate responses are generated. We review here the current hypotheses of nutrient sensing mechanisms of enteroendocrine cells, including the release of gut peptides, mainly cholecystokinin, glucagon-like peptide-1, and peptide YY, and subsequent gut-to-brain signaling pathways promoting a reduction of food intake and an increase in energy expenditure. Furthermore, this review highlights recent research suggesting this energy regulating gut-brain axis can be influenced by gut microbiota, potentially contributing to the development of obesity.

Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

USDA-ARS?s Scientific Manuscript database

Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

Persistent Organic Pollutants Modify Gut Microbiota–Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation

PubMed Central

Zhang, Limin; Nichols, Robert G.; Correll, Jared; Murray, Iain A.; Tanaka, Naoki; Smith, Philip B.; Hubbard, Troy D.; Sebastian, Aswathy; Albert, Istvan; Hatzakis, Emmanuel; Gonzalez, Frank J.; Perdew, Gary H.

2015-01-01

Background Alteration of the gut microbiota through diet and environmental contaminants may disturb physiological homeostasis, leading to various diseases including obesity and type 2 diabetes. Because most exposure to environmentally persistent organic pollutants (POPs) occurs through the diet, the host gastrointestinal tract and commensal gut microbiota are likely to be exposed to POPs. Objectives We examined the effect of 2,3,7,8-tetrachlorodibenzofuran (TCDF), a persistent environmental contaminant, on gut microbiota and host metabolism, and we examined correlations between gut microbiota composition and signaling pathways. Methods Six-week-old male wild-type and Ahr–/– mice on the C57BL/6J background were treated with 24 μg/kg TCDF in the diet for 5 days. We used 16S rRNA gene sequencing, 1H nuclear magnetic resonance (NMR) metabolomics, targeted ultra-performance liquid chromatography coupled with triplequadrupole mass spectrometry, and biochemical assays to determine the microbiota compositions and the physiological and metabolic effects of TCDF. Results Dietary TCDF altered the gut microbiota by shifting the ratio of Firmicutes to Bacteroidetes. TCDF-treated mouse cecal contents were enriched with Butyrivibrio spp. but depleted in Oscillobacter spp. compared with vehicle-treated mice. These changes in the gut microbiota were associated with altered bile acid metabolism. Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipogenesis, gluconeogenesis, and glycogenolysis in an AHR-dependent manner. Conclusion These findings provide new insights into the biochemical consequences of TCDF exposure involving the alteration of the gut microbiota, modulation of nuclear receptor signaling, and disruption of host metabolism. Citation Zhang L, Nichols RG, Correll J, Murray IA, Tanaka N, Smith PB

Cognitive Impairment by Antibiotic-Induced Gut Dysbiosis: Analysis of Gut Microbiota-Brain Communication

PubMed Central

Fröhlich, Esther E.; Farzi, Aitak; Mayerhofer, Raphaela; Reichmann, Florian; Jačan, Angela; Wagner, Bernhard; Zinser, Erwin; Bordag, Natalie; Magnes, Christoph; Fröhlich, Eleonore; Kashofer, Karl; Gorkiewicz, Gregor; Holzer, Peter

2016-01-01

Emerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. We hypothesized that the concerns related to antibiotic-induced gut dysbiosis can only adequately be addressed if the effect of intragastric treatment of adult mice with multiple antibiotics on (i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior is systematically investigated. Of the antibiotics used (ampicillin, bacitracin, meropenem, neomycin, vancomycin), ampicillin had some oral bioavailability but did not enter the brain. 16S rDNA sequencing confirmed antibiotic-induced microbial community disruption, and metabolomics revealed that gut dysbiosis was associated with depletion of bacteria-derived metabolites in the colon and alterations of lipid species and converted microbe-derived molecules in the plasma. Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis. PMID:26923630

Mango Supplementation Modulates Gut Microbial Dysbiosis and Short-Chain Fatty Acid Production Independent of Body Weight Reduction in C57BL/6 Mice Fed a High-Fat Diet.

PubMed

Ojo, Babajide; El-Rassi, Guadalupe Davila; Payton, Mark E; Perkins-Veazie, Penelope; Clarke, Stephen; Smith, Brenda J; Lucas, Edralin A

2016-08-01

High-fat (HF) diet-induced obesity is associated with changes in the gut microbiota. Fiber and other bioactive compounds in plant-based foods are suggested to prevent gut dysbiosis brought on by HF feeding. Mango is high in fiber and has been reported to have anti-obesogenic, hypoglycemic, and immunomodulatory properties. We investigated the effects of freeze-dried mango pulp combined with an HF diet on the cecal microbial population and its relation to body composition, lipids, glucose parameters, short-chain fatty acid (SCFA) production, and gut inflammatory markers in a mouse model of diet-induced obesity. Six-wk-old male C57BL/6 mice were randomly assigned to 1 of 4 dietary treatment groups: control (AIN-93M, 10% fat kcal), HF (60% fat kcal), and HF + 1% or 10% mango (HF+1%M or HF+10%M, wt:wt) for 12 wk. The cecal microbial population was assessed by use of 16S rDNA sequencing. Body composition, plasma glucose and lipids, cecal and fecal SCFAs, and mRNA abundance of inflammatory markers in the ileum and colonic lamina propria were assessed. Compared with the control group, HF feeding significantly reduced (P < 0.05) 1 operational taxonomic unit (OTU) of the genus Bifidobacteria (64-fold) and 5 OTUs of the genus Akkermansia (≥16-fold). This reduction was prevented in the HF+10%M group, members of which had 10% higher final body weight compared with the HF group (P = 0.01) and similar fasting blood glucose concentrations (P = 0.24). The HF+10%M group had 135% (P = 0.004) and 133% (P < 0.0001) greater fecal acetic and n-butyric acids concentrations than the HF group, suggesting greater microbial fermentation. Furthermore, a 59% greater colonic interleukin 10 (Il10) gene expression was observed in the HF+10%M group than in the HF group (P = 0.048), indicating modulation of gut inflammation. The HF+1%M group generally did not differ from the HF group. The addition of mango to an HF diet modulated the gut microbiota and production of SCFAs in C57BL/6 mice; these

Glucose metabolism: focus on gut microbiota, the endocannabinoid system and beyond.

PubMed

Cani, P D; Geurts, L; Matamoros, S; Plovier, H; Duparc, T

2014-09-01

The gut microbiota is now considered as a key factor in the regulation of numerous metabolic pathways. Growing evidence suggests that cross-talk between gut bacteria and host is achieved through specific metabolites (such as short-chain fatty acids) and molecular patterns of microbial membranes (lipopolysaccharides) that activate host cell receptors (such as toll-like receptors and G-protein-coupled receptors). The endocannabinoid (eCB) system is an important target in the context of obesity, type 2 diabetes (T2D) and inflammation. It has been demonstrated that eCB system activity is involved in the control of glucose and energy metabolism, and can be tuned up or down by specific gut microbes (for example, Akkermansia muciniphila). Numerous studies have also shown that the composition of the gut microbiota differs between obese and/or T2D individuals and those who are lean and non-diabetic. Although some shared taxa are often cited, there is still no clear consensus on the precise microbial composition that triggers metabolic disorders, and causality between specific microbes and the development of such diseases is yet to be proven in humans. Nevertheless, gastric bypass is most likely the most efficient procedure for reducing body weight and treating T2D. Interestingly, several reports have shown that the gut microbiota is profoundly affected by the procedure. It has been suggested that the consistent postoperative increase in certain bacterial groups such as Proteobacteria, Bacteroidetes and Verrucomicrobia (A. muciniphila) may explain its beneficial impact in gnotobiotic mice. Taken together, these data suggest that specific gut microbes modulate important host biological systems that contribute to the control of energy homoeostasis, glucose metabolism and inflammation in obesity and T2D. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Synergistic effects of Candida and Escherichia coli on gut barrier function.

PubMed

Diebel, L N; Liberati, D M; Diglio, C A; Dulchavsky, S A; Brown, W J

1999-12-01

Disruption of the indigenous gut microflora with overgrowth of gram-negative bacteria and Candida species is common in the critically ill patient. These organisms readily translocate in vitro, which may cause septic complications and organ failure. A synergistic effect between Escherichia coli and C. albicans in polymicrobial infections has been demonstrated. An interaction between these organisms at the mucosal barrier is unknown. Ca(CO2) monolayers were grown to confluence in a two compartment culture system. E. coli and C. albicans or E. coli alone were added to the apical chambers. Secretory immunoglobulin A was added to half of the apical chambers as well. Cell cultures were incubated for a total of 240 minutes. Basal media were sampled at timed intervals for quantitative culture. Monolayer integrity was confirmed by serial measurement of transepithelial electrical resistance. Secretory immunoglobulin A decreased bacterial translocation across Ca(CO2) monolayers challenged with E. coli alone. Transepithelial passage of E. coli was significantly increased by coculture of bacteria with C. albicans. Augmentation of bacterial translocation by Candida occurred even in the presence of secretory immunoglobulin A. Candida colonization of the GI tract may impair mucosal barrier defense against gram-negative bacteria. The clinical role of gut antifungal prophylaxis in protecting against gut derived gram-negative sepsis is speculative.

Cospeciation of gut microbiota with hominids

PubMed Central

Moeller, Andrew H.; Caro-Quintero, Alejandro; Mjungu, Deus; Georgiev, Alexander V.; Lonsdorf, Elizabeth V.; Muller, Martin N.; Pusey, Anne E.; Peeters, Martine; Hahn, Beatrice H.; Ochman, Howard

2016-01-01

The evolutionary origins of the bacterial lineages that populate the human gut are unknown. Here we show that multiple lineages of the predominant bacterial taxa in the gut arose via cospeciation with humans, chimpanzees, bonobos, and gorillas over the past 15 million years. Analyses of strain-level bacterial diversity within hominid gut microbiomes revealed that clades of Bacteroidaceae and Bifidobacteriaceae have been maintained exclusively within host lineages across hundreds of thousands of host generations. Divergence times of these cospeciating gut bacteria are congruent with those of hominids, indicating that nuclear, mitochondrial, and gut bacterial genomes diversified in concert during hominid evolution. This study identifies human gut bacteria descended from ancient symbionts that speciated simultaneously with humans and the African apes. PMID:27463672

Regulation of obesity-related insulin resistance with gut anti-inflammatory agents.

PubMed

Luck, Helen; Tsai, Sue; Chung, Jason; Clemente-Casares, Xavier; Ghazarian, Magar; Revelo, Xavier S; Lei, Helena; Luk, Cynthia T; Shi, Sally Yu; Surendra, Anuradha; Copeland, Julia K; Ahn, Jennifer; Prescott, David; Rasmussen, Brittany A; Chng, Melissa Hui Yen; Engleman, Edgar G; Girardin, Stephen E; Lam, Tony K T; Croitoru, Kenneth; Dunn, Shannon; Philpott, Dana J; Guttman, David S; Woo, Minna; Winer, Shawn; Winer, Daniel A

2015-04-07

Obesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited therapeutically. Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations. Reduction of the gut immune system, using beta7 integrin-deficient mice (Beta7(null)), decreases HFD-induced IR. Treatment of wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters. These beneficial effects are dependent on adaptive and gut immunity and are associated with reduced gut permeability and endotoxemia, decreased visceral adipose tissue inflammation, and improved antigen-specific tolerance to luminal antigens. Thus, the mucosal immune system affects multiple pathways associated with systemic IR and represents a novel therapeutic target in this disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Inulin-type fructan improves diabetic phenotype and gut microbiota profiles in rats

PubMed Central

Xin, Fengjiao; Yu, Xiaobing

2018-01-01

Background & Aims Accumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats. Methods A diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed. Results We found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck, G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3–V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Phascolarctobacterium, and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio, which

Gut bacteria mediate aggregation in the German cockroach

PubMed Central

Wada-Katsumata, Ayako; Zurek, Ludek; Nalyanya, Godfrey; Roelofs, Wendell L.; Zhang, Aijun; Schal, Coby

2015-01-01

Aggregation of the German cockroach, Blattella germanica, is regulated by fecal aggregation agents (pheromones), including volatile carboxylic acids (VCAs). We demonstrate that the gut microbial community contributes to production of these semiochemicals. Chemical analysis of the fecal extract of B. germanica revealed 40 VCAs. Feces from axenic cockroaches (no microorganisms in the alimentary tract) lacked 12 major fecal VCAs, and 24 of the remaining compounds were represented at extremely low amounts. Olfactory and aggregation bioassays demonstrated that nymphs strongly preferred the extract of control feces over the fecal extract of axenic cockroaches. Additionally, nymphs preferred a synthetic blend of 6 fecal VCAs over a solvent control or a previously identified VCA blend. To test whether gut bacteria contribute to the production of fecal aggregation agents, fecal aerobic bacteria were cultured, isolated, and identified. Inoculation of axenic cockroaches with individual bacterial taxa significantly rescued the aggregation response to the fecal extract, and inoculation with a mix of six bacterial isolates was more effective than with single isolates. The results indicate that the commensal gut microbiota contributes to production of VCAs that act as fecal aggregation agents and that cockroaches discriminate among the complex odors that emanate from a diverse microbial community. Our results highlight the pivotal role of gut bacteria in mediating insect–insect communication. Moreover, because the gut microbial community reflects the local environment, local plasticity in fecal aggregation pheromones enables colony-specific odors and fidelity to persistent aggregation sites. PMID:26644557

Nucleon decay in non-minimal supersymmetric SO(10)

NASA Astrophysics Data System (ADS)

Macpherson, Alick L.

1996-02-01

Evaluation of nucleon decay modes and branching ratios in a non-minimal supersymmetric SO(10) grand unified theory is presented. The non-minimal GUT considered is the supersymmetrised version of the 'realistic' SO(10) model originally proposed by Harvey, Reiss and Ramond, which is realistic in that it gives acceptable charged fermion and neutrino masses within the context of a phenomenological fit to the low-energy standard model inputs. Despite a complicated Higgs sector, the SO(10) 10 Higgs superfield mass insertion is found to be the sole contribution to the tree-level F-term governing nucleon decay. The resulting dimension-5 operators that mediate nucleon decay give branching ratio predictions parameterised by a single parameter, the ratio of the Yukawa couplings of the 10 to the fermion generations. For parameter values corresponding to a lack of dominance of the third family self-coupling, the dominant nucleon decay modes are p → K + + overlineνμand n → K 0 + overlineνμ as expected. Further, the charged muon decay modes are enhanced by two orders of magnitude over the standard minimal SUSY SU(5) predictions, thus predicting a distinct spectrum of 'visible' modes. These charged muon decay modes, along with p → π + + overlineνμand n → π 0 + overlineνμ, which are moderately enhanced over the SUSY SU(5) prediction, suggest a distinguishing fingerprint of this particular GUT model, and if nucleon decay is observed at Super-KAMIOKANDE the predicted branching ratio spectrum can be used to determine the validity of this 'realistic' SO(10) SUSY GUT model.

Fatty Liver Accompanies an Increase in Lactobacillus Species in the Hind Gut of C57BL/6 Mice Fed a High-Fat Diet123

PubMed Central

Zeng, Huawei; Liu, Jun; Jackson, Matthew I.; Zhao, Feng-Qi; Yan, Lin; Combs, Gerald F.

2013-01-01

High-fat (HF) diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease and changes in the gut microbiome. To test the hypothesis that HF feeding increases certain predominant hind gut bacteria and development of steatohepatitis, C57BL/6 mice were fed an HF (45% energy) or low-fat (LF) (10% energy) diet for 10 wk. At the end of the feeding period, body weights in the HF group were 34% greater than those in the LF group (P < 0.05). These changes were associated with dramatic increases in lipid droplet number and size, inflammatory cell infiltration, and inducible nitric oxide (NO) synthase protein concentration in the livers of mice fed the HF diet. Consistent with the fatty liver phenotype, plasma leptin and tumor necrosis factor-α concentrations were also elevated in mice fed the HF diet, indicative of chronic inflammation. Eight of 12 pairs of polymerase chain reaction (PCR) primers for bacterial species that typically predominate hind gut microbial ecology generated specific PCR products from the fecal DNA samples. The amount of DNA from Lactobacillus gasseri and/or Lactobacillus taiwanensis in the HF group was 6900-fold greater than that in the LF group. Many of these bacteria are bile acid resistant and are capable of bile acid deconjugation. Because bile acids are regulators of hepatic lipid metabolism, the marked increase of gut L. gasseri and/or L. taiwanensis species bacteria with HF feeding may play a role in development of steatohepatitis in this model. PMID:23486979

Effects of sleeve gastrectomy on the composition and diurnal oscillation of gut microbiota related to the metabolic improvements.

PubMed

Shao, Yikai; Shen, Qiwei; Hua, Rong; Evers, Simon S; He, Kai; Yao, Qiyuan

2018-06-01

Disruptions of the composition and diurnal oscillation of gut microbiota are involved in metabolic disorders. To identify alterations in both the composition and diurnal oscillation of gut microbiota after high-fat diet (HFD) feeding and sleeve gastrectomy (SG) related to host metabolic status. University laboratories. Twenty-one 6-week-old male C57 BL/6 J mice were randomized on an HFD (n = 14) or normal chow (NC, n = 7). After 14 weeks of feeding, HFD-induced obese mice were randomized to receive either SG or sham surgery (n = 7 in each group). Fecal samples were collected every 6 hours over a 24-hour period at 14 weeks of NC or HFD feeding and subsequently 8 weeks after surgery. The composition and diurnal oscillation of gut microbiota were characterized using next-generation Illumina sequencing of 16 S rDNA. HFD feeding led to adiposity, disrupted composition, and impaired diurnal oscillation of gut microbiota relative to NC. After surgery, SG mice had considerable weight loss, improved glucose tolerance, and insulin sensitivity compared with sham mice. SG restored the reduced richness and disruptions in the composition of gut microbiota. The diminished diurnal oscillation of gut microbiota was improved after SG. SG not only changed the disrupted composition of gut microbiota toward that of NC feeding, but also improved the dampened diurnal oscillation of gut microbiota due to HFD feeding. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.

PubMed

Rizzetto, Lisa; Fava, Francesca; Tuohy, Kieran M; Selmi, Carlo

2018-05-31

Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in

Real-time analysis of gut flora in Entamoeba histolytica infected patients of Northern India

PubMed Central

2012-01-01

Background Amebic dysentery is caused by the protozoan parasite Entamoeba histolytica and the ingestion of quadrinucleate cyst of E. histolytica from fecally contaminated food or water initiates infection. Excystation occurs in the lumen of small intestine, where motile and potentially invasive trophozoites germinate from cysts. The ability of trophozoites to interact and digest gut bacteria is apparently important for multiplication of the parasite and its pathogenicity; however the contribution of resident bacterial flora is not well understood. We quantified the population of Bacteroides, Bifidobacterium, Ruminococcus, Lactobacillus, Clostridium leptum subgroup, Clostridium coccoides subgroup, Eubacterium, Campylobacter, Methanobrevibacter smithii and Sulphur reducing bacteria using genus specific primers in healthy (N = 22) vs amebic patients (E. histolytica positive, N = 17) stool samples by Real-time PCR. Results Absolute quantification of Bacteroides (p = .001), Closrtridium coccoides subgroup (p = 0.002), Clostridium leptum subgroup (p = 0.0001), Lactobacillus (p = 0.037), Campylobacter (p = 0.0014) and Eubacterium (p = 0.038) show significant drop in their population however, significant increase in Bifdobacterium (p = 0.009) was observed where as the population of Ruminococcus (p = 0.33) remained unaltered in healthy vs amebic patients (E. histolytica positive). We also report high prevalence of nimE gene in stool samples of both healthy volunteers and amebic patients. No significant decrease in nimE gene copy number was observed before and after the treatment with antiamebic drug. Conclusions Our results show significant alteration in predominant gut bacteria in E. histolytica infected individuals. The frequent episodes of intestinal amoebic dysentery thus result in depletion of few predominant genera in gut that may lead to poor digestion and absorption of food in intestine. It further disturbs the homeostasis

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis.

PubMed

Seal, John B; Alverdy, John C; Zaborina, Olga; An, Gary

2011-09-19

There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed--i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data--i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design--i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new investigatory avenues proposed to test those

E6^E7, a Novel Splice Isoform Protein of Human Papillomavirus 16, Stabilizes Viral E6 and E7 Oncoproteins via HSP90 and GRP78

PubMed Central

Ajiro, Masahiko

2015-01-01

ABSTRACT Transcripts of human papillomavirus 16 (HPV16) E6 and E7 oncogenes undergo alternative RNA splicing to produce multiple splice isoforms. However, the importance of these splice isoforms is poorly understood. Here we report a critical role of E6^E7, a novel isoform containing the 41 N-terminal amino acid (aa) residues of E6 and the 38 C-terminal aa residues of E7, in the regulation of E6 and E7 stability. Through mass spectrometric analysis, we identified that HSP90 and GRP78, which are frequently upregulated in cervical cancer tissues, are two E6^E7-interacting proteins responsible for the stability and function of E6^E7, E6, and E7. Although GRP78 and HSP90 do not bind each other, GRP78, but not HSP90, interacts with E6 and E7. E6^E7 protein, in addition to self-binding, interacts with E6 and E7 in the presence of GRP78 and HSP90, leading to the stabilization of E6 and E7 by prolonging the half-life of each protein. Knocking down E6^E7 expression in HPV16-positive CaSki cells by a splice junction-specific small interfering RNA (siRNA) destabilizes E6 and E7 and prevents cell growth. The same is true for the cells with a GRP78 knockdown or in the presence of an HSP90 inhibitor. Moreover, mapping and alignment analyses for splicing elements in 36 alpha-HPVs (α-HPVs) suggest the possible expression of E6^E7 mostly by other oncogenic or possibly oncogenic α-HPVs (HPV18, -30, -31, -39, -42, -45, -56, -59, -70, and -73). HPV18 E6^E7 is detectable in HPV18-positive HeLa cells and HPV18-infected raft tissues. All together, our data indicate that viral E6^E7 and cellular GRP78 or HSP90 might be novel targets for cervical cancer therapy. PMID:25691589

The gut mycobiome of the Human Microbiome Project healthy cohort.

PubMed

Nash, Andrea K; Auchtung, Thomas A; Wong, Matthew C; Smith, Daniel P; Gesell, Jonathan R; Ross, Matthew C; Stewart, Christopher J; Metcalf, Ginger A; Muzny, Donna M; Gibbs, Richard A; Ajami, Nadim J; Petrosino, Joseph F

2017-11-25

Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene. Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents. Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that

Role of the normal gut microbiota.

PubMed

Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Nageshwar Reddy, D

2015-08-07

Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

Marked alterations in the distal gut microbiome linked to diet-induced obesity

PubMed Central

Turnbaugh, Peter J.; Backhed, Fredrik; Fulton, Lucinda; Gordon, Jeffrey I.

2013-01-01

SUMMARY We have investigated the inter-relationship between diet, gut microbial ecology and energy balance using a mouse model of obesity produced by consumption of a prototypic Western diet. Diet-induced obesity (DIO) produced a bloom in a single uncultured clade within the Mollicutes class of the Firmicutes, which became the dominant lineage within the distal gut microbiota. This bloom was diminished by subsequent dietary manipulations that limit weight gain and reduce adiposity. Transplantation of the microbiota from mice with DIO to lean germ-free recipients produced a significantly greater increase in adiposity than transplants from lean donors. Metagenomic sequencing of the gut microbiome, biochemical assays, plus sequencing and in silico metabolic reconstructions of a related human gut-associated Mollicute (E.dolichum), revealed features that may provide a competitive advantage for members of the bloom in the Western diet nutrient milieu, including genes involved in import and metabolism of simple sugars. Our study illustrates how combining comparative metagenomics with gnotobiotic mouse models and specific dietary manipulations can disclose the niches of previously uncharacterized members of the gut microbiota. PMID:18407065

Derivation and characterization of gut-like structures from embryonic stem cells.

PubMed

Yamada, Takatsugu; Nakajima, Yoshiyuki

2006-01-01

Embryonic stem (ES) cells have a pluripotent ability to differentiate into a variety of cell lineages of all three embryonic germ layers in vitro. The hanging drop culture of ES cell suspension in the absence of leukemia inhibitory factor induces aggregation and differentiation of the cells into simple or cystic embryoid bodies (EBs). After 6 d of hanging drop culture, the resulting EBs are plated onto plastic dishes for the outgrowth culture. At d 21 after outgrowth culture, cell populations of EBs can give rise to three-dimensional gut-like structures that exhibit spontaneous contraction and highly coordinated peristalsis. The gut-like structures have large lumens surrounded by three layers: epithelium, lamina propria, and muscularis. Ganglia are scattered along the periphery, and interstitial cells of Cajal are distributed among the smooth muscle cells. The fundamental process of formation of the in vitro organized gut-like structures is similar to embryonic gastrointestinal development in vivo. The EBs at the 6-d egg-cylinder stage may have the potential to regulate developmental programs associated with cell lineage commitment and provide an appropriate microenvironment to differentiate ES cells into enteric derivatives of all three embryonic germ layers and reproduce the gut organization process in vitro.

Gut Microbiota and Metabolic Disorders

PubMed Central

Hur, Kyu Yeon

2015-01-01

Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders. PMID:26124989

Gut microbiota signatures of longevity.

PubMed

Kong, Fanli; Hua, Yutong; Zeng, Bo; Ning, Ruihong; Li, Ying; Zhao, Jiangchao

2016-09-26

An aging global population poses substantial challenges to society [1]. Centenarians are a model for healthy aging because they have reached the extreme limit of life by escaping, surviving, or delaying chronic diseases [2]. The genetics of centenarians have been extensively examined [3], but less is known about their gut microbiotas. Recently, Biagi et al.[4] characterized the gut microbiota in Italian centenarians and semi-supercentenarians. Here, we compare the gut microbiota of Chinese long-living people with younger age groups, and with the results from the Italian population [4], to identify gut-microbial signatures of healthy aging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues.

PubMed

Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei

2017-10-01

Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.

Finding viable models in SUSY parameter spaces with signal specific discovery potential

NASA Astrophysics Data System (ADS)

Burgess, Thomas; Lindroos, Jan Øye; Lipniacka, Anna; Sandaker, Heidi

2013-08-01

Recent results from ATLAS giving a Higgs mass of 125.5 GeV, further constrain already highly constrained supersymmetric models such as pMSSM or CMSSM/mSUGRA. As a consequence, finding potentially discoverable and non-excluded regions of model parameter space is becoming increasingly difficult. Several groups have invested large effort in studying the consequences of Higgs mass bounds, upper limits on rare B-meson decays, and limits on relic dark matter density on constrained models, aiming at predicting superpartner masses, and establishing likelihood of SUSY models compared to that of the Standard Model vis-á-vis experimental data. In this paper a framework for efficient search for discoverable, non-excluded regions of different SUSY spaces giving specific experimental signature of interest is presented. The method employs an improved Markov Chain Monte Carlo (MCMC) scheme exploiting an iteratively updated likelihood function to guide search for viable models. Existing experimental and theoretical bounds as well as the LHC discovery potential are taken into account. This includes recent bounds on relic dark matter density, the Higgs sector and rare B-mesons decays. A clustering algorithm is applied to classify selected models according to expected phenomenology enabling automated choice of experimental benchmarks and regions to be used for optimizing searches. The aim is to provide experimentalist with a viable tool helping to target experimental signatures to search for, once a class of models of interest is established. As an example a search for viable CMSSM models with τ-lepton signatures observable with the 2012 LHC data set is presented. In the search 105209 unique models were probed. From these, ten reference benchmark points covering different ranges of phenomenological observables at the LHC were selected.

Pathophysiology of the gut and the microbiome in the host response

PubMed Central

Lyons, John D.; Coopersmith, Craig M.

2016-01-01

Objective To describe and summarize the data supporting the “gut” as the motor driving critical illness and multiple organ dysfunction syndrome (MODS) presented at the Eunice Kennedy Shriver National Institute of Child Health and Human Development MODS Workshop (March 26–27, 2015). Data Sources Summary of workshop keynote presentation. Study Selection Not applicable. Data Extraction Presented by an expert in the field, the data assessing the role of gastrointestinal dysfunction driving critical illness were described with a focus on identifying knowledge gaps and research priorities. Data Synthesis Summary of presentation and discussion supported and supplemented by relevant literature. Conclusions The understanding of gut dysfunction in critical illness has evolved greatly over time, and the gut is now often considered as the “motor” of critical illness. The association of the gut with critical illness is supported by both animal models and clinical studies. Initially, the association between gut dysfunction and critical illness focused primarily on bacterial translocation into the bloodstream. However, that work has evolved to include other gut-derived products causing distant injury via other routes (e.g. lymphatics). Additionally, alterations in the gut epithelium may be associated with critical illness and influence outcomes. Gut epithelial apoptosis, intestinal hyperpermeability and perturbations in the intestinal mucus layer have all been associated with critical illness. Finally, there is growing evidence that the intestinal microbiome plays a crucial role in mediating pathology in critical illness. Further research is needed to better understand the role of each of these mechanisms and their contribution to MODS in children. PMID:28248833

The human gut microbiome as a screening tool for colorectal cancer.

PubMed

Zackular, Joseph P; Rogers, Mary A M; Ruffin, Mack T; Schloss, Patrick D

2014-11-01

Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information. ©2014 American Association for Cancer Research.

Potential Role of the Gut Microbiome in ALS: A Systematic Review.

PubMed

Wright, Michelle L; Fournier, Christina; Houser, Madelyn C; Tansey, Malú; Glass, Jonathan; Hertzberg, Vicki Stover

2018-01-01

Amyotrophic lateral sclerosis (ALS) etiology and pathophysiology are not well understood. Recent data suggest that dysbiosis of gut microbiota may contribute to ALS etiology and progression. This review aims to explore evidence of associations between gut microbiota and ALS etiology and pathophysiology. Databases were searched for publications relevant to the gut microbiome in ALS. Three publications provided primary evidence of changes in microbiome profiles in ALS. An ALS mouse model revealed damaged tight junction structure and increased permeability in the intestine versus controls along with a shifted microbiome profile, including decreased levels of butyrate-producing bacteria. In a subsequent publication, again using an ALS mouse model, researchers showed that dietary supplementation with butyrate relieved symptoms and lengthened both time to onset of weight loss and survival time. In a small study of ALS patients and healthy controls, investigators also found decreased levels of butyrate-producing bacteria. Essential for maintaining gut barrier integrity, butyrate is the preferred energy source of intestinal epithelial cells. Ten other articles were reviews and commentaries providing indirect support for a role of gut microbiota in ALS pathophysiology. Thus, these studies provide a modicum of evidence implicating gut microbiota in ALS disease, although more research is needed to confirm the connection and determine pathophysiologic mechanisms. Nurses caring for these patients need to understand the gut microbiome and its potential role in ALS in order to effectively counsel patients and their families about emerging therapies (e.g., prebiotics, probiotics, and fecal microbial transplant) and their off-label uses.

Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota.

PubMed

Malo, M S; Alam, S Nasrin; Mostafa, G; Zeller, S J; Johnson, P V; Mohammad, N; Chen, K T; Moss, A K; Ramasamy, S; Faruqui, A; Hodin, S; Malo, P S; Ebrahimi, F; Biswas, B; Narisawa, S; Millán, J L; Warren, H S; Kaplan, J B; Kitts, C L; Hohmann, E L; Hodin, R A

2010-11-01

The intestinal microbiota plays a critical role in maintaining human health; however, the mechanisms governing the normal homeostatic number and composition of these microbes are largely unknown. Previously it was shown that intestinal alkaline phosphatase (IAP), a small intestinal brush border enzyme, functions as a gut mucosal defence factor limiting the translocation of gut bacteria to mesenteric lymph nodes. In this study the role of IAP in the preservation of the normal homeostasis of the gut microbiota was investigated. Bacterial culture was performed in aerobic and anaerobic conditions to quantify the number of bacteria in the stools of wild-type (WT) and IAP knockout (IAP-KO) C57BL/6 mice. Terminal restriction fragment length polymorphism, phylogenetic analyses and quantitative real-time PCR of subphylum-specific bacterial 16S rRNA genes were used to determine the compositional profiles of microbiotas. Oral supplementation of calf IAP (cIAP) was used to determine its effects on the recovery of commensal gut microbiota after antibiotic treatment and also on the colonisation of pathogenic bacteria. IAP-KO mice had dramatically fewer and also different types of aerobic and anaerobic microbes in their stools compared with WT mice. Oral supplementation of IAP favoured the growth of commensal bacteria, enhanced restoration of gut microbiota lost due to antibiotic treatment and inhibited the growth of a pathogenic bacterium (Salmonella typhimurium). IAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections.

Diet rapidly and reproducibly alters the human gut microbiome

PubMed Central

David, Lawrence A.; Maurice, Corinne F.; Carmody, Rachel N.; Gootenberg, David B.; Button, Julie E.; Wolfe, Benjamin E.; Ling, Alisha V.; Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.; Biddinger, Sudha B.; Dutton, Rachel J.; Turnbaugh, Peter J.

2013-01-01

Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut1–5, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals2, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease6. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. PMID:24336217

E6AP is Required for Human Papillomavirus type 16 E6 to Cause Cervical Cancer in Mice

PubMed Central

Shai, Anny; Pitot, Henry C.; Lambert, Paul F.

2010-01-01

High-risk human papillomaviruses cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins including Bak, E6BP1, E6TP1, and proteins that contain PDZ domains such as hScrib and hDlg. Many of these activities are thought to contribute to E6’s role in carcinogenesis. E6’s interaction with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through E6’s ability to recruit the ubiquitin ligase, E6AP into complexes with these cellular proteins resulting in their ubiquitin–mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating E6's acute and oncogenic phenotypes, including induction of epithelial hyperplasia, abrogation of DNA damage response and induction of cervical cancer. Loss of E6AP had no discernable effect on E6's ability to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of E6’s oncogenic potential in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer. PMID:20530688

The Maternal Gut Microbiome During Pregnancy.

PubMed

Edwards, Sara M; Cunningham, Solveig A; Dunlop, Anne L; Corwin, Elizabeth J

The gut microbiome is a critical component of an individual's metabolism and overall health. The prenatal period is marked by unique inflammatory and immune changes that alter maternal gut function and bacterial composition as the pregnancy advances. The composition of the maternal gut microbiome contributes to obstetric outcomes with long-term health sequelae for mother and child. Estrogen and progesterone also have an impact on gut function, especially during the prenatal period. These physiologic changes in pregnancy allow for adjustments in maternal metabolism and weight necessary to support the pregnancy. Normal hormonal, metabolic, and immunologic changes to the maternal gut microbiome throughout the prenatal period are reviewed, including relevant implications for nurses providing care for pregnant women.

Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract.

PubMed

Toh, Michael C; Goodyear, Mara; Daigneault, Michelle; Allen-Vercoe, Emma; Van Raay, Terence J

2013-06-01

The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.

Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.

PubMed

Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M

2015-10-01

Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.

GUTs on Compact Type IIB Orientifolds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blumenhagen, Ralph; /Munich, Max Planck Inst.; Braun, Volker

We systematically analyze globally consistent SU(5) GUT models on intersecting D7-branes in genuine Calabi-Yau orientifolds with O3- and O7-planes. Beyond the well-known tadpole and K-theory cancellation conditions there exist a number of additional subtle but quite restrictive constraints. For the realization of SU(5) GUTs with gauge symmetry breaking via U(1)Y flux we present two classes of suitable Calabi-Yau manifolds defined via del Pezzo transitions of the elliptically fibred hypersurface P{sub 1,1,1,6,9}[18] and of the Quintic P{sub 1,1,1,1,1}[5], respectively. To define an orientifold projection we classify all involutions on del Pezzo surfaces. We work out the model building prospects of thesemore » geometries and present five globally consistent string GUT models in detail, including a 3-generation SU(5) model with no exotics whatsoever. We also realize other phenomenological features such as the 10 10 5{sub H} Yukawa coupling and comment on the possibility of moduli stabilization, where we find an entire new set of so-called swiss-cheese type Calabi-Yau manifolds. It is expected that both the general constrained structure and the concrete models lift to F-theory vacua on compact Calabi-Yau fourfolds.« less

Gut dysbiosis and detection of "live gut bacteria" in blood of Japanese patients with type 2 diabetes.

PubMed

Sato, Junko; Kanazawa, Akio; Ikeda, Fuki; Yoshihara, Tomoaki; Goto, Hiromasa; Abe, Hiroko; Komiya, Koji; Kawaguchi, Minako; Shimizu, Tomoaki; Ogihara, Takeshi; Tamura, Yoshifumi; Sakurai, Yuko; Yamamoto, Risako; Mita, Tomoya; Fujitani, Yoshio; Fukuda, Hiroshi; Nomoto, Koji; Takahashi, Takuya; Asahara, Takashi; Hirose, Takahisa; Nagata, Satoru; Yamashiro, Yuichiro; Watada, Hirotaka

2014-08-01

Mounting evidence indicates that the gut microbiota are an important modifier of obesity and diabetes. However, so far there is no information on gut microbiota and "live gut bacteria" in the systemic circulation of Japanese patients with type 2 diabetes. Using a sensitive reverse transcription-quantitative PCR (RT-qPCR) method, we determined the composition of fecal gut microbiota in 50 Japanese patients with type 2 diabetes and 50 control subjects, and its association with various clinical parameters, including inflammatory markers. We also analyzed the presence of gut bacteria in blood samples. The counts of the Clostridium coccoides group, Atopobium cluster, and Prevotella (obligate anaerobes) were significantly lower (P < 0.05), while the counts of total Lactobacillus (facultative anaerobes) were significantly higher (P < 0.05) in fecal samples of diabetic patients than in those of control subjects. Especially, the counts of Lactobacillus reuteri and Lactobacillus plantarum subgroups were significantly higher (P < 0.05). Gut bacteria were detected in blood at a significantly higher rate in diabetic patients than in control subjects (28% vs. 4%, P < 0.01), and most of these bacteria were Gram-positive. This is the first report of gut dysbiosis in Japanese patients with type 2 diabetes as assessed by RT-qPCR. The high rate of gut bacteria in the circulation suggests translocation of bacteria from the gut to the bloodstream. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Search for beyond standard model physics (non-SUSY) in final states with photons at the Tevatron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palencia, Jose Enrique; /Fermilab

2009-01-01

We present the results of searches for non-standard model phenomena in photon final states. These searches use data from integrated luminosities of {approx} 1-4 fb{sup -1} of p{bar p} collisions at {radical}s = 1.96 TeV, collected with the CDF and D0 detectors at the Fermilab Tevatron. No significant excess in data has been observed. We report limits on the parameters of several BSM models (excluding SUSY) for events containing photons.

Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

PubMed Central

Martinez-Zapien, Denise; Ruiz, Francesc Xavier; Poirson, Juline; Mitschler, André; Ramirez-Ramos, Juan; Forster, Anne; Cousido-Siah, Alexandra; Masson, Murielle; Pol, Scott Vande; Podjarny, Alberto; Travé, Gilles; Zanier, Katia

2015-01-01

Summary The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers 1, p53 is degraded by the viral oncoprotein E6 2. In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 4. Neither E6 nor E6AP are separately able to recruit p53 3,5, and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis. PMID:26789255

Parkinson’s Disease and PD Medications Have Distinct Signatures of the Gut Microbiome

PubMed Central

Hill-Burns, Erin M.; Debelius, Justine W.; Morton, James T.; Wissemann, William T.; Lewis, Matthew R.; Wallen, Zachary D.; Peddada, Shyamal D.; Factor, Stewart A.; Molho, Eric; Zabetian, Cyrus P.; Knight, Rob; Payami, Haydeh

2017-01-01

Background There is mounting evidence for a connection between the gut and Parkinson’s disease (PD). Dysbiosis of gut microbiota could explain several features of PD. Objective To determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research. Methods 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways. Results Independent microbial signatures were detected for PD (P=4E-5), subjects’ region of residence within the United States (P=3E-3), age (P=0.03), sex (P=1E-3) and dietary fruits/vegetables (P=0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P=4E-4), anticholinergics (P=5E-3), and possibly carbidopa/levodopa (P=0.05). We found significantly altered abundance of Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways including metabolism of plant-derived compounds and xenobiotics degradation. Conclusion PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. PMID:28195358

Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease.

PubMed

Pistollato, Francesca; Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

2016-10-01

It has been hypothesized that alterations in the composition of the gut microbiota might be associated with the onset of certain human pathologies, such as Alzheimer disease, a neurodegenerative syndrome associated with cerebral accumulation of amyloid-β fibrils. It has been shown that bacteria populating the gut microbiota can release significant amounts of amyloids and lipopolysaccharides, which might play a role in the modulation of signaling pathways and the production of proinflammatory cytokines related to the pathogenesis of Alzheimer disease. Additionally, nutrients have been shown to affect the composition of the gut microbiota as well as the formation and aggregation of cerebral amyloid-β. This suggests that modulating the gut microbiome and amyloidogenesis through specific nutritional interventions might prove to be an effective strategy to prevent or reduce the risk of Alzheimer disease. This review examines the possible role of the gut in the dissemination of amyloids, the role of the gut microbiota in the regulation of the gut-brain axis, the potential amyloidogenic properties of gut bacteria, and the possible impact of nutrients on modulation of microbiota composition and amyloid formation in relation to the pathogenesis of Alzheimer disease. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gut Microbiota Dysbiosis in Obesity-Linked Metabolic Diseases and Prebiotic Potential of Polyphenol-Rich Extracts.

PubMed

Anhê, Fernando F; Varin, Thibault V; Le Barz, Mélanie; Desjardins, Yves; Levy, Emile; Roy, Denis; Marette, André

2015-12-01

Trillions of microorganisms inhabit the human body, strongly colonizing the gastro-intestinal tract and outnumbering our own cells. High-throughput sequencing techniques and new bioinformatic tools have enabled scientists to extend our knowledge on the relationship between the gut microbiota and host's physiology. Disruption of the ecological equilibrium in the gut (i.e., dysbiosis) has been associated with several pathological processes, including obesity and its related comorbidities, with diet being a strong determinant of gut microbial balance. In this review, we discuss the potential prebiotic effect of polyphenol-rich foods and extracts and how they can reshape the gut microbiota, emphasizing the novel role of the mucin-degrading bacterium Akkermansia muciniphila in their metabolic benefits.

On `light' fermions and proton stability in `big divisor' D3/ D7 large volume compactifications

NASA Astrophysics Data System (ADS)

Misra, Aalok; Shukla, Pramod

2011-06-01

Building on our earlier work (Misra and Shukla, Nucl. Phys. B 827:112, 2010; Phys. Lett. B 685:347-352, 2010), we show the possibility of generating "light" fermion mass scales of MeV-GeV range (possibly related to the first two generations of quarks/leptons) as well as eV (possibly related to first two generations of neutrinos) in type IIB string theory compactified on Swiss-Cheese orientifolds in the presence of a mobile space-time filling D3-brane restricted to (in principle) stacks of fluxed D7-branes wrapping the "big" divisor Σ B . This part of the paper is an expanded version of the latter half of Sect. 3 of a published short invited review (Misra, Mod. Phys. Lett. A 26:1, 2011) written by one of the authors [AM]. Further, we also show that there are no SUSY GUT-type dimension-five operators corresponding to proton decay, and we estimate the proton lifetime from a SUSY GUT-type four-fermion dimension-six operator to be 1061 years. Based on GLSM calculations in (Misra and Shukla, Nucl. Phys. B 827:112, 2010) for obtaining the geometric Kähler potential for the "big divisor," using further the Donaldson's algorithm, we also briefly discuss in the first of the two appendices the metric for the Swiss-Cheese Calabi-Yau used, which we obtain and which becomes Ricci flat in the large-volume limit.

Gut microbiome and its role in cardiovascular diseases.

PubMed

Ahmadmehrabi, Shadi; Tang, W H Wilson

2017-11-01

In recent years, an interest in intestinal microbiota-host interactions has increased due to many findings about the impact of gut bacteria on human health and disease. Dysbiosis, a change in the composition of the gut microbiota, has been associated with much pathology, including cardiovascular diseases (CVD). This article will review normal functions of the gut microbiome, its link to CVD, and potential therapeutic interventions. The recently discovered contribution of gut microbiota-derived molecules in the development of heart disease and its risk factors has significantly increased attention towards the connection between our gut and heart. The gut microbiome is virtually an endocrine organ, arguably the largest, capable of contributing to and reacting to circulating signaling molecules within the host. Gut microbiota-host interactions occur through many pathways, including trimethylamine-N-oxide and short-chain fatty acids. These molecules and others have been linked to much pathology including chronic kidney disease, atherosclerosis, and hypertension. Although our understanding of gut microbiota-host interactions has increased recently; many questions remain about the mechanistic links between the gut microbiome and CVD. With further research, we may one day be able to add gut microbiota profiles as an assessable risk factor for CVD and target therapies towards the gut microbiota.

Prebiotic Potential of a Maize-Based Soluble Fibre and Impact of Dose on the Human Gut Microbiota.

PubMed

Costabile, Adele; Deaville, Eddie R; Morales, Agustin Martin; Gibson, Glenn R

2016-01-01

Dietary management of the human gut microbiota towards a more beneficial composition is one approach that may improve host health. To date, a large number of human intervention studies have demonstrated that dietary consumption of certain food products can result in significant changes in the composition of the gut microbiota i.e. the prebiotic concept. Thus the prebiotic effect is now established as a dietary approach to increase beneficial gut bacteria and it has been associated with modulation of health biomarkers and modulation of the immune system. Promitor™ Soluble Corn Fibre (SCF) is a well-known maize-derived source of dietary fibre with potential selective fermentation properties. Our aim was to determine the optimum prebiotic dose of tolerance, desired changes to microbiota and fermentation of SCF in healthy adult subjects. A double-blind, randomised, parallel study was completed where volunteers (n = 8/treatment group) consumed 8, 14 or 21 g from SCF (6, 12 and 18 g/fibre delivered respectively) over 14-d. Over the range of doses studied, SCF was well tolerated Numbers of bifidobacteria were significantly higher for the 6 g/fibre/day compared to 12 g and 18 g/fibre delivered/day (mean 9.25 and 9.73 Log10 cells/g fresh faeces in the pre-treatment and treatment periods respectively). Such a numerical change of 0.5 Log10 bifidobacteria/g fresh faeces is consistent with those changes observed for inulin-type fructans, which are recognised prebiotics. A possible prebiotic effect of SCF was therefore demonstrated by its stimulation of bifidobacteria numbers in the overall gut microbiota during a short-term intervention.

Gut bacteria facilitate adaptation to crop rotation in the western corn rootworm

PubMed Central

Chu, Chia-Ching; Spencer, Joseph L.; Curzi, Matías J.; Zavala, Jorge A.; Seufferheld, Manfredo J.

2013-01-01

Insects are constantly adapting to human-driven landscape changes; however, the roles of their gut microbiota in these processes remain largely unknown. The western corn rootworm (WCR, Diabrotica virgifera virgifera LeConte) (Coleoptera: Chrysomelidae) is a major corn pest that has been controlled via annual rotation between corn (Zea mays) and nonhost soybean (Glycine max) in the United States. This practice selected for a “rotation-resistant” variant (RR-WCR) with reduced ovipositional fidelity to cornfields. When in soybean fields, RR-WCRs also exhibit an elevated tolerance of antiherbivory defenses (i.e., cysteine protease inhibitors) expressed in soybean foliage. Here we show that gut bacterial microbiota is an important factor facilitating this corn specialist’s (WCR's) physiological adaptation to brief soybean herbivory. Comparisons of gut microbiota between RR- and wild-type WCR (WT-WCR) revealed concomitant shifts in bacterial community structure with host adaptation to soybean diets. Antibiotic suppression of gut bacteria significantly reduced RR-WCR tolerance of soybean herbivory to the level of WT-WCR, whereas WT-WCR were unaffected. Our findings demonstrate that gut bacteria help to facilitate rapid adaptation of insects in managed ecosystems. PMID:23798396

33 CFR 117.537 - Townsend Gut.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Townsend Gut. 117.537 Section 117... OPERATION REGULATIONS Specific Requirements Maine § 117.537 Townsend Gut. The draw of the Southport (SR27) Bridge, at mile 0.7, across Townsend Gut between Boothbay Harbor and Southport, Maine shall open on...

Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment.

PubMed

Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

2016-01-01

The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being.

Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment

PubMed Central

Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

2016-01-01

The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being. PMID:27416027

[Profiles of cell proliferation and apoptosis in the mouse epithelial regeneration model K6b-E6/E7].

PubMed

Bonilla-Delgado, José; Rodríguez-Uribe, Genaro; Cortés-Malagón, Enoc Mariano; Sierra Martínez, Mónica; Acosta-Altamirano, Gustavo; Gariglio-Vidal, Patricio

2012-01-01

Mammals have limited epithelial regeneration capacity. The K6b-E6/E7 mice model has been described as useful for the study of epithelial regeneration. The objective of this study is to compare the expression of E6/E7 oncogenes with those of cell proliferation and apoptosis during epithelization. The hypothesis of this study is that alterations in cell proliferation and apoptosis in K6b-E6/E7 mice will only occur during epithelization. Deep 2 mm punches were performed in the middle of transgenic and control mice's ears. A biopsy was collected from the epithelization zone 72 hours and 2 weeks post-injury. Assays for cell proliferation and apoptosis were carried out by immunohistochemistry and TUNEL techniques, respectively. RT-PCR in situ was performed to compare E6/E7 expressions in the areas studied. Transgenic strain K6b-E6/E7 presented more proliferative cells and less apoptotic cells in epithelizated zones. This effect was limited to suprabasal stratum only, and correlates with E6/E7 oncogenes expression. Two weeks post-injury, cell proliferation and apoptosis were similar in both samples as the E6/E7 expression went down. K6b-E6/E7 mouse model is useful for epithelial regeneration. Its mechanisms should be considered for the treatment of deep wounds.

Absence of Gut Microbiota Reduces Emotional Reactivity in Japanese Quails (Coturnix japonica).

PubMed

Kraimi, Narjis; Calandreau, Ludovic; Biesse, Manon; Rabot, Sylvie; Guitton, Edouard; Velge, Philippe; Leterrier, Christine

2018-01-01

Background: Recent studies have demonstrated an effect of the gut microbiota on brain development and behavior leading to the concept of the microbiota-gut-brain axis. However, its effect on behavior in birds is unknown. The aim of the present study was to determine the effect of the absence of gut microbiota on emotional reactivity in birds by comparing germ-free (GF) quails to those colonized (COL) with gut microbiota. Material and Methods: From hatching, the quails of both groups GF ( n = 36) and COL ( n = 36) were reared in sterile isolators. The COL quails were colonized at day 2 by introducing a pool of droppings from conventional adult females into the drinking water and feed. The quails were weighed individually on day 2, 6, and 14. From day 8, emotional reactivity was assessed in each group in the isolators through several behavioral tests. Results: GF quails showed a considerable decrease in emotional reactivity demonstrated by spending less time in tonic immobility during the tonic immobility test (242 s ± 31 vs. 331 s ± 32, p ≤ 0.05), traveling a shorter distance (3,897 cm ± 242 vs. 4,827 cm ± 278, p ≤ 0.05) at a lower velocity (6.55 cm/s ± 0.4 vs. 8.1 cm/s ± 0.5, p ≤ 0.05) during the social separation test and spending more time near an object at the beginning of the novel object test (33.7 s ± 6.4 vs. 18.5 s ± 4.1, p ≤ 0.05). No difference in growth was found between the 2 groups. Conclusion: For the first time, this study demonstrates that the absence of gut microbiota reduces emotional reactivity in Japanese quails in situations of fear and social perturbation without influence on growth.

Absence of Gut Microbiota Reduces Emotional Reactivity in Japanese Quails (Coturnix japonica)

PubMed Central

Kraimi, Narjis; Calandreau, Ludovic; Biesse, Manon; Rabot, Sylvie; Guitton, Edouard; Velge, Philippe; Leterrier, Christine

2018-01-01

Background: Recent studies have demonstrated an effect of the gut microbiota on brain development and behavior leading to the concept of the microbiota-gut-brain axis. However, its effect on behavior in birds is unknown. The aim of the present study was to determine the effect of the absence of gut microbiota on emotional reactivity in birds by comparing germ-free (GF) quails to those colonized (COL) with gut microbiota. Material and Methods: From hatching, the quails of both groups GF (n = 36) and COL (n = 36) were reared in sterile isolators. The COL quails were colonized at day 2 by introducing a pool of droppings from conventional adult females into the drinking water and feed. The quails were weighed individually on day 2, 6, and 14. From day 8, emotional reactivity was assessed in each group in the isolators through several behavioral tests. Results: GF quails showed a considerable decrease in emotional reactivity demonstrated by spending less time in tonic immobility during the tonic immobility test (242 s ± 31 vs. 331 s ± 32, p ≤ 0.05), traveling a shorter distance (3,897 cm ± 242 vs. 4,827 cm ± 278, p ≤ 0.05) at a lower velocity (6.55 cm/s ± 0.4 vs. 8.1 cm/s ± 0.5, p ≤ 0.05) during the social separation test and spending more time near an object at the beginning of the novel object test (33.7 s ± 6.4 vs. 18.5 s ± 4.1, p ≤ 0.05). No difference in growth was found between the 2 groups. Conclusion: For the first time, this study demonstrates that the absence of gut microbiota reduces emotional reactivity in Japanese quails in situations of fear and social perturbation without influence on growth. PMID:29881357

Gut microbiota imbalance and colorectal cancer

PubMed Central

Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde

2016-01-01

The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603

E6-associated protein is required for human papillomavirus type 16 E6 to cause cervical cancer in mice.

PubMed

Shai, Anny; Pitot, Henry C; Lambert, Paul F

2010-06-15

High-risk human papillomaviruses (HPV) cause certain anogenital and head and neck cancers. E6, one of three potent HPV oncogenes that contribute to the development of these malignancies, is a multifunctional protein with many biochemical activities. Among these activities are its ability to bind and inactivate the cellular tumor suppressor p53, induce expression of telomerase, and bind to various other proteins, including Bak, E6BP1, and E6TP1, and proteins that contain PDZ domains, such as hScrib and hDlg. Many of these activities are thought to contribute to the role of E6 in carcinogenesis. The interaction of E6 with many of these cellular proteins, including p53, leads to their destabilization. This property is mediated at least in part through the ability of E6 to recruit the ubiquitin ligase E6-associated protein (E6AP) into complexes with these cellular proteins, resulting in their ubiquitin-mediated degradation by the proteasome. In this study, we address the requirement for E6AP in mediating acute and oncogenic phenotypes of E6, including induction of epithelial hyperplasia, abrogation of DNA damage response, and induction of cervical cancer. Loss of E6AP had no discernible effect on the ability of E6 to induce hyperplasia or abrogate DNA damage responses, akin to what we had earlier observed in the mouse epidermis. Nevertheless, in cervical carcinogenesis studies, there was a complete loss of the oncogenic potential of E6 in mice nulligenic for E6AP. Thus, E6AP is absolutely required for E6 to cause cervical cancer.

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats.

PubMed

Gao, Jin-Hang; Wen, Shi-Lei; Tong, Huan; Wang, Chun-Hui; Yang, Wen-Juan; Tang, Shi-Hang; Yan, Zhao-Ping; Tai, Yang; Ye, Cheng; Liu, Rui; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Tang, Cheng-Wei

2016-06-01

Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis. Copyright © 2016 the American Physiological Society.

Gut immunity in Lepidopteran insects.

PubMed

Wu, Kai; Yang, Bing; Huang, Wuren; Dobens, Leonard; Song, Hongsheng; Ling, Erjun

2016-11-01

Lepidopteran insects constitute one of the largest fractions of animals on earth, but are considered pests in their relationship with man. Key to the success of this order of insects is its ability to digest food and absorb nutrition, which takes place in the midgut. Because environmental microorganisms can easily enter Lepidopteran guts during feeding, the innate immune response guards against pathogenic bacteria, virus and microsporidia that can be devoured with food. Gut immune responses are complicated by both resident gut microbiota and the surrounding peritrophic membrane and are distinct from immune responses in the body cavity, which depend on the function of the fat body and hemocytes. Due to their relevance to agricultural production, studies of Lepidopteran insect midgut and immunity are receiving more attention, and here we summarize gut structures and functions, and discuss how these confer immunity against different microorganisms. It is expected that increased knowledge of Lepidopteran gut immunity may be utilized for pest biological control in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

The E6 and E7 genes of human papillomavirus type 6 have weak immortalizing activity in human epithelial cells.

PubMed Central

Halbert, C L; Demers, G W; Galloway, D A

1992-01-01

Previous studies have shown that the E7 gene of human papillomavirus (HPV) type 16 or 18 alone was sufficient for immortalization of human foreskin epithelial cells (HFE) and that the efficiency was increased in cooperation with the respective E6 gene, whereas the HPV6 E6 or E7 gene was not active in HFE. To detect weak immortalizing activities of the HPV6 genes, cells were infected with recombinant retroviruses containing HPV genes, alone and in homologous and heterologous combinations. The HPV6 genes, alone or together (HPV6 E6 plus HPV6 E7), were not able to immortalize cells. However the HPV6 E6 gene, in concert with HPV16 E7, increased the frequency of immortalization threefold over that obtained with HPV16 E7 alone. Interestingly, 6 of 20 clones containing the HPV16 E6 gene and the HPV6 E7 gene were immortalized, whereas neither gene alone was sufficient. Thus, the HPV6 E6 and E7 genes have weak immortalizing activities which can be detected in cooperation with the more active transforming genes of HPV16. Acute expression of the HPV6 and HPV16 E6 and E7 genes revealed that only HPV16 E7 was able to stimulate the proliferation of cells in organotypic culture, resulting in increased expression of the proliferative cell nuclear antigen and the formation of a disorganized epithelial layer. Additionally, combinations of genes that immortalized HFE cells (HPV16 E6 plus HPV16 E7, HPV16 E6 plus HPV6 E7, and HPV6 E6 plus HPV16 E7) also stimulated proliferation. Images PMID:1312623

Healthy human gut phageome

PubMed Central

Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; van der Oost, John; de Vos, Willem M.; Young, Mark J.

2016-01-01

The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20–50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health. PMID:27573828

Healthy human gut phageome.

PubMed

Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

2016-09-13

The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis

PubMed Central

2011-01-01

Background There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. Methodology/Principal Findings An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed - i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data - i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design - i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new

COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

PubMed

Gao, Shujun; Fang, Lekun; Phan, Liem Minh; Qdaisat, Aiham; Yeung, Sai-Ching J; Lee, Mong-Hong

2015-09-29

Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.

The Underlying Ecological Processes of Gut Microbiota Among Cohabitating Retarded, Overgrown and Normal Shrimp.

PubMed

Xiong, Jinbo; Dai, Wenfang; Zhu, Jinyong; Liu, Keshao; Dong, Chunming; Qiu, Qiongfen

2017-05-01

Increasing evidence of tight links among the gut microbiota, obesity, and host health has emerged, but knowledge of the ecological processes that shape the variation in microbial assemblages across growth rates remains elusive. Moreover, inadequately control for differences in factors that profoundly affect the gut microbial community, hampers evaluation of the gut microbiota roles in regulating growth rates. To address this gap, we evaluated the composition and ecological processes of the gut bacterial community in cohabitating retarded, overgrown, and normal shrimps from identically managed ponds. Gut bacterial community structures were distinct (P = 0.0006) among the shrimp categories. Using a structural equation modeling (SEM), we found that changes in the gut bacterial community were positively related to digestive activities, which subsequently affected shrimp growth rate. This association was further supported by intensified interspecies interaction and enriched lineages with high nutrient intake efficiencies in overgrown shrimps. However, the less phylogenetic clustering of gut microbiota in overgrown and retarded subjects may offer empty niches for pathogens invasion, as evidenced by higher abundances of predicted functional pathways involved in disease infection. Given no differences in biotic and abiotic factors among the cohabitating shrimps, we speculated that the distinct gut community assembly could be attributed to random colonization in larval shrimp (e.g., priority effects) and that an altered microbiota could be a causative factor in overgrowth or retardation in shrimp. To our knowledge, this is the first study to provide an integrated overview of the direct roles of gut microbiota in shaping shrimp growth rate and the underlying ecological mechanisms.

Brain Gut Microbiome Interactions and Functional Bowel Disorders

PubMed Central

Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

2014-01-01

Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

Beneficial Effect of Bidens pilosa on Body Weight Gain, Food Conversion Ratio, Gut Bacteria and Coccidiosis in Chickens

PubMed Central

Chang, Cicero L. T.; Chung, Chih-Yao; Kuo, Chih-Horng; Kuo, Tien-Fen; Yang, Chu-Wen; Yang, Wen-Chin

2016-01-01

In the interests of food safety and public health, plants and their compounds are now re-emerging as an alternative approach to treat gastrointestinal diseases in chickens. Here, we studied the impact of the edible medicinal plant, B. pilosa, on growth performance, gut bacteria and coccidiosis in chickens. First, we found that B. pilosa significantly elevated body weight gain and lowered feed conversion ratio in chickens. Next, we showed that B. pilosa reduced cecal damage as evidenced by increased hemorrhage, villus destruction and decreased villus-to-crypt ratio in chicken ceca. We also performed pyrosequencing of the PCR ampilcons based on the 16S rRNA genes of gut bacteria in chickens. Metagenomic analysis indicated that the chicken gut bacteria belonged to 6 phyla, 6 classes, 6 orders, 9 families, and 8 genera. More importantly, we found that B. pilosa affected the composition of bacteria. This change in bacteria composition was correlated with body weight gain, feed conversion ratio and gut pathology in chickens. Collectively, this work suggests that B. pilosa has beneficial effects on growth performance and protozoan infection in chickens probably via modulation of gut bacteria. PMID:26765226

Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice.

PubMed

Lam, Yan Y; Ha, Connie W Y; Hoffmann, Jenny M A; Oscarsson, Jan; Dinudom, Anuwat; Mather, Thomas J; Cook, David I; Hunt, Nicholas H; Caterson, Ian D; Holmes, Andrew J; Storlien, Len H

2015-07-01

To distinguish the effects of dietary fat profile on gut parameters and their relationships with metabolic changes and to determine the capacity of n-3 fatty acids to modify gut variables in the context of diet-induced metabolic dysfunctions. Mice received control or high-fat diets emphasizing saturated (HFD-sat), n-6 (HFD-n6), or n-3 (HFD-n3) fatty acids for 8 weeks. In another cohort, mice that were maintained on HFD-sat received n-3-rich fish oil or resolvin D1 supplementation. HFD-sat and HFD-n6 induced similar weight gain, but only HFD-sat increased index of insulin resistance (HOMA-IR), colonic permeability, and mesenteric fat inflammation. Hydrogen sulfide-producing bacteria were one of the major groups driving the diet-specific changes in gut microbiome, with the overall microbial profile being associated with changes in body weight, HOMA-IR, and gut permeability. In mice maintained on HFD-sat, fish oil and resolvin D1 restored barrier function and reduced inflammation in the colon but were unable to normalize HOMA-IR. Different dietary fat profiles led to distinct intestinal and metabolic outcomes that are independent of obesity. Interventions targeting inflammation successfully restored gut health but did not reverse systemic aspects of diet-induced metabolic dysfunction, implicating separation between gut dysfunctions and disease-initiating and/or -maintaining processes. © 2015 The Obesity Society.

Linking the Gut Microbial Ecosystem with the Environment: Does Gut Health Depend on Where We Live?

PubMed Central

Tasnim, Nishat; Abulizi, Nijiati; Pither, Jason; Hart, Miranda M.; Gibson, Deanna L.

2017-01-01

Global comparisons reveal a decrease in gut microbiota diversity attributed to Western diets, lifestyle practices such as caesarian section, antibiotic use and formula-feeding of infants, and sanitation of the living environment. While gut microbial diversity is decreasing, the prevalence of chronic inflammatory diseases such as inflammatory bowel disease, diabetes, obesity, allergies and asthma is on the rise in Westernized societies. Since the immune system development is influenced by microbial components, early microbial colonization may be a key factor in determining disease susceptibility patterns later in life. Evidence indicates that the gut microbiota is vertically transmitted from the mother and this affects offspring immunity. However, the role of the external environment in gut microbiome and immune development is poorly understood. Studies show that growing up in microbe-rich environments, such as traditional farms, can have protective health effects on children. These health-effects may be ablated due to changes in the human lifestyle, diet, living environment and environmental biodiversity as a result of urbanization. Importantly, if early-life exposure to environmental microbes increases gut microbiota diversity by influencing patterns of gut microbial assembly, then soil biodiversity loss due to land-use changes such as urbanization could be a public health threat. Here, we summarize key questions in environmental health research and discuss some of the challenges that have hindered progress toward a better understanding of the role of the environment on gut microbiome development. PMID:29056933

Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China

PubMed Central

Xie, Haiyang; Li, Ang; Lu, Haifeng; Xu, Shaoyan; Zhou, Lin; Zhang, Hua; Cui, Guangying; Chen, Xinhua; Liu, Yuanxing; Wu, Liming; Qin, Nan; Sun, Ranran; Wang, Wei; Li, Lanjuan; Wang, Weilin; Zheng, Shusen

2017-01-01

Pancreatic carcinoma (PC) is a lethal cancer. Gut microbiota is associated with some risk factors of PC, e.g. obesity and types II diabetes. However, the specific gut microbial profile in clinical PC in China has never been reported. This prospective study collected 85 PC and 57 matched healthy controls (HC) to analyze microbial characteristics by MiSeq sequencing. The results showed that gut microbial diversity was decreased in PC with an unique microbial profile, which partly attributed to its decrease of alpha diversity. Microbial alterations in PC featured by the increase of certain pathogens and lipopolysaccharides-producing bacteria, and the decrease of probiotics and butyrate-producing bacteria. Microbial community in obstruction cases was separated from the un-obstructed cases. Streptococcus was associated with the bile. Furthermore, 23 microbial functions e.g. Leucine and LPS biosynthesis were enriched, while 13 functions were reduced in PC. Importantly, based on 40 genera associated with PC, microbial markers achieves a high classification power with AUC of 0.842. In conclusion, gut microbial profile was unique in PC, providing a microbial marker for non-invasive PC diagnosis. PMID:29221120

Innate immunity and gut-microbe mutualism in Drosophila.

PubMed

Ryu, Ji-Hwan; Ha, Eun-Mi; Lee, Won-Jae

2010-04-01

Metazoan guts face a wide variety of microorganisms upon exposure to the environment, including beneficial symbionts, non-symbionts, food-borne microbes and life-threatening pathogens. Recent evidence has shown that the innate immunity of gut epithelia, such as anti-microbial peptide- and reactive oxygen species-based immune systems, actively participate in gut-microbe homeostasis by shaping the commensal community while efficiently eliminating unwanted bacteria. Therefore, elucidation of the regulatory mechanism by which gut innate immunity occurs at the molecular level will provide a novel perspective of gut-microbe mutualisms as well as of gut diseases caused by alterations in the innate immunity.

Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome.

PubMed

Hill-Burns, Erin M; Debelius, Justine W; Morton, James T; Wissemann, William T; Lewis, Matthew R; Wallen, Zachary D; Peddada, Shyamal D; Factor, Stewart A; Molho, Eric; Zabetian, Cyrus P; Knight, Rob; Payami, Haydeh

2017-05-01

There is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD. The objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research. A total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways. Independent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation. PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society. © 2017

Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE-/- mice.

PubMed

Vujic, Nemanja; Korbelius, Melanie; Leopold, Christina; Duta-Mare, Madalina; Rainer, Silvia; Schlager, Stefanie; Goeritzer, Madeleine; Kolb, Dagmar; Eichmann, Thomas O; Diwoky, Clemens; Zimmer, Andreas; Zimmermann, Robert; Lass, Achim; Radovic, Branislav; Kratky, Dagmar

2017-05-16

Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (-/-) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)-/- mice, an established animal model for dyslipidemia and atherosclerosis. In the current study, we investigated functional consequences of MGL deficiency on lipid and energy metabolism in ApoE/MGL double knockout (DKO) mice. MGL deficiency affected hepatic cholesterol metabolism by causing increased cholesterol elimination via the biliary pathway. Moreover, DKO mice exhibit lipid-triggered delay in gastric emptying without major effects on overall triglyceride and cholesterol absorption. The observed phenotype of DKO mice is likely not a consequence of potentiated CB1R signaling but rather dependent on the activation of alternative signaling pathways. We conclude that MGL deficiency causes complex metabolic changes including cholesterol metabolism and regulation of gut transit independent of the endocannabinoid system.

Two dynamic regimes in the human gut microbiome

PubMed Central

Smillie, Chris S.; Alm, Eric J.

2017-01-01

The gut microbiome is a dynamic system that changes with host development, health, behavior, diet, and microbe-microbe interactions. Prior work on gut microbial time series has largely focused on autoregressive models (e.g. Lotka-Volterra). However, we show that most of the variance in microbial time series is non-autoregressive. In addition, we show how community state-clustering is flawed when it comes to characterizing within-host dynamics and that more continuous methods are required. Most organisms exhibited stable, mean-reverting behavior suggestive of fixed carrying capacities and abundant taxa were largely shared across individuals. This mean-reverting behavior allowed us to apply sparse vector autoregression (sVAR)—a multivariate method developed for econometrics—to model the autoregressive component of gut community dynamics. We find a strong phylogenetic signal in the non-autoregressive co-variance from our sVAR model residuals, which suggests niche filtering. We show how changes in diet are also non-autoregressive and that Operational Taxonomic Units strongly correlated with dietary variables have much less of an autoregressive component to their variance, which suggests that diet is a major driver of microbial dynamics. Autoregressive variance appears to be driven by multi-day recovery from frequent facultative anaerobe blooms, which may be driven by fluctuations in luminal redox. Overall, we identify two dynamic regimes within the human gut microbiota: one likely driven by external environmental fluctuations, and the other by internal processes. PMID:28222117

Two dynamic regimes in the human gut microbiome.

PubMed

Gibbons, Sean M; Kearney, Sean M; Smillie, Chris S; Alm, Eric J

2017-02-01

The gut microbiome is a dynamic system that changes with host development, health, behavior, diet, and microbe-microbe interactions. Prior work on gut microbial time series has largely focused on autoregressive models (e.g. Lotka-Volterra). However, we show that most of the variance in microbial time series is non-autoregressive. In addition, we show how community state-clustering is flawed when it comes to characterizing within-host dynamics and that more continuous methods are required. Most organisms exhibited stable, mean-reverting behavior suggestive of fixed carrying capacities and abundant taxa were largely shared across individuals. This mean-reverting behavior allowed us to apply sparse vector autoregression (sVAR)-a multivariate method developed for econometrics-to model the autoregressive component of gut community dynamics. We find a strong phylogenetic signal in the non-autoregressive co-variance from our sVAR model residuals, which suggests niche filtering. We show how changes in diet are also non-autoregressive and that Operational Taxonomic Units strongly correlated with dietary variables have much less of an autoregressive component to their variance, which suggests that diet is a major driver of microbial dynamics. Autoregressive variance appears to be driven by multi-day recovery from frequent facultative anaerobe blooms, which may be driven by fluctuations in luminal redox. Overall, we identify two dynamic regimes within the human gut microbiota: one likely driven by external environmental fluctuations, and the other by internal processes.

Gut microbiota and malnutrition.

PubMed

Million, Matthieu; Diallo, Aldiouma; Raoult, Didier

2017-05-01

Malnutrition is the leading cause of death worldwide in children under the age of five, and is the focus of the first World Health Organization (WHO) Millennium Development Goal. Breastfeeding, food and water security are major protective factors against malnutrition and critical factors in the maturation of healthy gut microbiota, characterized by a transient bifidobacterial bloom before a global rise in anaerobes. Early depletion in gut Bifidobacterium longum, a typical maternal probiotic, known to inhibit pathogens, represents the first step in gut microbiota alteration associated with severe acute malnutrition (SAM). Later, the absence of the Healthy Mature Anaerobic Gut Microbiota (HMAGM) leads to deficient energy harvest, vitamin biosynthesis and immune protection, and is associated with diarrhea, malabsorption and systemic invasion by microbial pathogens. A therapeutic diet and infection treatment may be unable to restore bifidobacteria and HMAGM. Besides refeeding and antibiotics, future trials including non-toxic missing microbes and nutrients necessary to restore bifidobacteria and HMAGM, including prebiotics and antioxidants, are warranted in children with severe or refractory disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adaptive immune education by gut microbiota antigens.

PubMed

Zhao, Qing; Elson, Charles O

2018-05-01

Host-microbiota mutualism has been established during long-term co-evolution. A diverse and rich gut microbiota plays an essential role in the development and maturation of the host immune system. Education of the adaptive immune compartment by gut microbiota antigens is important in establishing immune balance. In particular, a critical time frame immediately after birth provides a 'window of opportunity' for the development of lymphoid structures, differentiation and maturation of T and B cells and, most importantly, establishment of immune tolerance to gut commensals. Depending on the colonization niche, antigen type and metabolic property of different gut microbes, CD4 T-cell responses vary greatly, which results in differentiation into distinct subsets. As a consequence, certain bacteria elicit effector-like immune responses by promoting the production of pro-inflammatory cytokines such as interferon-γ and interleukin-17A, whereas other bacteria favour the generation of regulatory CD4 T cells and provide help with gut homeostasis. The microbiota have profound effects on B cells also. Gut microbial exposure leads to a continuous diversification of B-cell repertoire and the production of T-dependent and -independent antibodies, especially IgA. These combined effects of the gut microbes provide an elegant educational process to the adaptive immune network. Contrariwise, failure of this process results in a reduced homeostasis with the gut microbiota, and an increased susceptibility to various immune disorders, both inside and outside the gut. With more definitive microbial-immune relations waiting to be discovered, modulation of the host gut microbiota has a promising future for disease intervention. © 2018 John Wiley & Sons Ltd.

A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0654 TITLE: A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS...Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Major Tasks and subtasks: Aim#1: To compare the gut microbiome of subjects with RMS and PPMS. Major Task 1: To seek and obtain HRPO approval Major

A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0652 TITLE: A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS...0652 A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...SOW, each Aim was subdivided into Major Tasks and subtasks: Aim#1: To compare the gut microbiome of subjects with RMS and PPMS. Major Task 1

Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota.

PubMed

Serino, Matteo; Luche, Elodie; Gres, Sandra; Baylac, Audrey; Bergé, Mathieu; Cenac, Claire; Waget, Aurelie; Klopp, Pascale; Iacovoni, Jason; Klopp, Christophe; Mariette, Jerome; Bouchez, Olivier; Lluch, Jerome; Ouarné, Francoise; Monsan, Pierre; Valet, Philippe; Roques, Christine; Amar, Jacques; Bouloumié, Anne; Théodorou, Vassilia; Burcelin, Remy

2012-04-01

The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

Biotransformation of aesculin by human gut bacteria and identification of its metabolites in rat urine.

PubMed

Ding, Wei-Jun; Deng, Yun; Feng, Hao; Liu, Wei-Wei; Hu, Rong; Li, Xiang; Gu, Zhe-Ming; Dong, Xiao-Ping

2009-03-28

To observe the biotransformation process of a Chinese compound, aesculin, by human gut bacteria, and to identify its metabolites in rat urine. Representative human gut bacteria were collected from 20 healthy volunteers, and then utilized in vitro to biotransform aesculin under anaerobic conditions. At 0, 2, 4, 8, 12, 16, 24, 48 and 72 h post-incubation, 10 mL of culture medium was collected. Metabolites of aesculin were extracted 3 x from rat urine with methanol and analyzed by HPLC. For in vivo metabolite analysis, aesculetin (100 mg/kg) was administered to rats via stomach gavage, rat urine was collected from 6 to 48 h post-administration, and metabolite analysis was performed by LC/ESI-MS and MS/MS in the positive and negative modes. Human gut bacteria could completely convert aesculin into aesculetin in vitro. The biotransformation process occurred from 8 to 24 h post-incubation, with its highest activity was seen from 8 to 12 h. The in vitro process was much slower than the in vivo process. In contrast to the in vitro model, six aesculetin metabolites were identified in rat urine, including 6-hydroxy-7-gluco-coumarin (M1), 6-hydroxy-7-sulf-coumarin (M2), 6, 7-di-gluco-coumarin (M3), 6-glc-7-gluco-coumarin (M4), 6-O-methyl-7-gluco-coumarin (M5) and 6-O-methyl-7-sulf-coumarin (M6). Of which, M2 and M6 were novel metabolites. Aesculin can be transferred into aesculetin by human gut bacteria and is further modified by the host in vivo. The diverse metabolites of aesculin may explain its pleiotropic pharmaceutical effects.

Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

PubMed

Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

2017-02-01

There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

Bound state solution of Dirac equation for 3D harmonics oscillator plus trigonometric scarf noncentral potential using SUSY QM approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cari, C., E-mail: carinln@yahoo.com; Suparmi, A., E-mail: carinln@yahoo.com

2014-09-30

Dirac equation of 3D harmonics oscillator plus trigonometric Scarf non-central potential for spin symmetric case is solved using supersymmetric quantum mechanics approach. The Dirac equation for exact spin symmetry reduces to Schrodinger like equation. The relativistic energy and wave function for spin symmetric case are simply obtained using SUSY quantum mechanics method and idea of shape invariance.

Preservation of three-dimensional spatial structure in the gut microbiome.

PubMed

Hasegawa, Yuko; Mark Welch, Jessica L; Rossetti, Blair J; Borisy, Gary G

2017-01-01

Preservation of three-dimensional structure in the gut is necessary in order to analyze the spatial organization of the gut microbiota and gut luminal contents. In this study, we evaluated preparation methods for mouse gut with the goal of preserving micron-scale spatial structure while performing fluorescence imaging assays. Our evaluation of embedding methods showed that commonly used media such as Tissue-Tek Optimal Cutting Temperature (OCT) compound, paraffin, and polyester waxes resulted in redistribution of luminal contents. By contrast, a hydrophilic methacrylate resin, Technovit H8100, preserved three-dimensional organization. Our mouse intestinal preparation protocol optimized using the Technovit H8100 embedding method was compatible with microbial fluorescence in situ hybridization (FISH) and other labeling techniques, including immunostaining and staining with both wheat germ agglutinin (WGA) and 4', 6-diamidino-2-phenylindole (DAPI). Mucus could be visualized whether the sample was fixed with paraformaldehyde (PFA) or with Carnoy's fixative. The protocol optimized in this study enabled simultaneous visualization of micron-scale spatial patterns formed by microbial cells in the mouse intestines along with biogeographical landmarks such as host-derived mucus and food particles.

Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type.

PubMed

Lee, Min-Jung; Kang, Mi-Jin; Lee, So-Yeon; Lee, Eun; Kim, Kangjin; Won, Sungho; Suh, Dong In; Kim, Kyung Won; Sheen, Youn Ho; Ahn, Kangmo; Kim, Bong-Soo; Hong, Soo-Jong

2018-04-01

Perturbations of the infant gut microbiota can shape development of the immune system and link to the risk of allergic diseases. We sought to understand the role of the gut microbiome in patients with atopic dermatitis (AD). The metagenome of the infant gut microbiome was analyzed according to feeding types. Composition of the gut microbiota was analyzed in fecal samples from 129 infants (6 months old) by using pyrosequencing, including 66 healthy infants and 63 infants with AD. The functional profile of the gut microbiome was analyzed by means of whole-metagenome sequencing (20 control subjects and 20 patients with AD). In addition, the total number of bacteria in the feces was determined by using real-time PCR. The gut microbiome of 6-month-old infants was different based on feeding types, and 2 microbiota groups (Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in the feces were lower in infants with AD than in control infants. Although no specific taxa directly correlated with AD in 16S rRNA gene results, whole-metagenome analysis revealed differences in functional genes related to immune development. The reduction in genes for oxidative phosphorylation, phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide-binding domain-like receptor signaling, and antigen processing and presentation induced by reduced colonization of mucin-degrading bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was significantly associated with stunted immune development in the AD group compared with the control group (P < .05). Alterations in the gut microbiome can be associated with AD because of different bacterial genes that can modulate host immune cell function. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome.

PubMed

Xiao, Shuiming; Fei, Na; Pang, Xiaoyan; Shen, Jian; Wang, Linghua; Zhang, Baorang; Zhang, Menghui; Zhang, Xiaojun; Zhang, Chenhong; Li, Min; Sun, Lifeng; Xue, Zhengsheng; Wang, Jingjing; Feng, Jie; Yan, Feiyan; Zhao, Naisi; Liu, Jiaqi; Long, Wenmin; Zhao, Liping

2014-02-01

Chronic inflammation induced by endotoxin from a dysbiotic gut microbiota contributes to the development of obesity-related metabolic disorders. Modification of gut microbiota by a diet to balance its composition becomes a promising strategy to help manage obesity. A dietary scheme based on whole grains, traditional Chinese medicinal foods, and prebiotics (WTP diet) was designed to meet human nutritional needs as well as balance the gut microbiota. Ninety-three of 123 central obese volunteers (BMI ≥ 28 kg m(-2) ) completed a self-controlled clinical trial consisting of 9-week intervention on WTP diet followed by a 14-week maintenance period. The average weight loss reached 5.79 ± 4.64 kg (6.62 ± 4.94%), in addition to improvement in insulin sensitivity, lipid profiles, and blood pressure. Pyrosequencing of fecal samples showed that phylotypes related to endotoxin-producing opportunistic pathogens of Enterobacteriaceae and Desulfovibrionaceae were reduced significantly, while those related to gut barrier-protecting bacteria of Bifidobacteriaceae increased. Gut permeability, measured as lactulose/mannitol ratio, was decreased compared with the baseline. Plasma endotoxin load as lipopolysaccharide-binding protein was also significantly reduced, with concomitant decrease in tumor necrosis factor-α, interleukin-6, and an increase in adiponectin. These results suggest that modulation of the gut microbiota via dietary intervention may enhance the intestinal barrier integrity, reduce circulating antigen load, and ultimately ameliorate the inflammation and metabolic phenotypes. © 2013 The Authors. FEMS Microbiology Ecology pubished by John Wiley & Sons Ltd on behalf of the Federation of European Microbiological Societies.

Gut dysfunction in Parkinson's disease

PubMed Central

Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

2016-01-01

Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

SO(10) Yukawa unification after the first run of the LHC

NASA Astrophysics Data System (ADS)

Raby, Stuart

2014-06-01

In this talk we discuss SO(10) Yukawa unification and its ramifications for phenomenology. The initial constraints come from fitting the top, bottom and tau masses, requiring large tan β ˜ 50 and particular values for soft SUSY breaking parameters. We perform a global χ2 analysis, fitting the recently observed `Higgs' with mass of order 125 GeV in addition to fermion masses and mixing angles and several flavor violating observables. We discuss two distinct GUT scale boundary conditions for soft SUSY breaking masses. In both cases we have a universal cubic scalar parameter, A0. In the first case we consider universal gaugino masses, and universal scalar masses, m16, for squarks and sleptons; while in the latter case we have non-universal gaugino masses and either universal scalar masses, m16, for squarks and sleptons or D-term splitting of scalar masses. We discuss the spectrum of SUSY particle masses and consequences for the LHC.

Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer.

PubMed

Tsuruya, Atsuki; Kuwahara, Akika; Saito, Yuta; Yamaguchi, Haruhiko; Tsubo, Takahisa; Suga, Shogo; Inai, Makoto; Aoki, Yuichi; Takahashi, Seiji; Tsutsumi, Eri; Suwa, Yoshihide; Morita, Hidetoshi; Kinoshita, Kenji; Totsuka, Yukari; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Mizukami, Takeshi; Yokoyama, Akira; Shimoyama, Takefumi; Nakayama, Toru

2016-06-13

Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic. However, the effects of chronic ethanol consumption on the human gut microbiome are poorly understood, and the role of gut microbes in the proposed AcH-mediated pathogenesis of ER-CRC remains to be elaborated. Here we analyse and compare the gut microbiota structures of non-alcoholics and alcoholics. The gut microbiotas of alcoholics were diminished in dominant obligate anaerobes (e.g., Bacteroides and Ruminococcus) and enriched in Streptococcus and other minor species. This alteration might be exacerbated by habitual smoking. These observations could at least partly be explained by the susceptibility of obligate anaerobes to reactive oxygen species, which are increased by chronic exposure of the gut mucosa to ethanol. The AcH productivity from ethanol was much lower in the faeces of alcoholic patients than in faeces of non-alcoholic subjects. The faecal phenotype of the alcoholics could be rationalised based on their gut microbiota structures and the ability of gut bacteria to accumulate AcH from ethanol.

Brane SUSY breaking and the gravitino mass

NASA Astrophysics Data System (ADS)

Kitazawa, Noriaki

2018-04-01

Supergravity models with spontaneously broken supersymmetry have been widely investigated over the years, together with some notable non-linear limits. Although in these models the gravitino becomes naturally massive absorbing the degrees of freedom of a Nambu-Goldstone fermion, there are cases in which the naive counting of degrees of freedom does not apply, in particular because of the absence of explicit gravitino mass terms in unitary gauge. The corresponding models require non-trivial de Sitter-like backgrounds, and it becomes of interest to clarify the fate of their Nambu-Goldstone modes. We elaborate on the fact that these non-trivial backgrounds can accommodate, consistently, gravitino fields carrying a number of degrees of freedom that is intermediate between those of massless and massive fields in a flat spacetime. For instance, in a simple supergravity model of this type with de Sitter background, the overall degrees of freedom of gravitino are as many as for a massive spin-3/2 field in flat spacetime, while the gravitino remains massless in the sense that it undergoes null-cone propagation in the stereographic picture. On the other hand, in the ten-dimensional USp(32) Type I Sugimoto model with "brane SUSY breaking", which requires a more complicated background, the degrees of freedom of gravitino are half as many of those of a massive one, and yet it somehow behaves again as a massless one.

Immune-modulatory genomic properties differentiate gut microbiota of infants with and without eczema.

PubMed

Oh, Seungdae; Yap, Gaik Chin; Hong, Pei-Ying; Huang, Chiung-Hui; Aw, Marion M; Shek, Lynette Pei-Chi; Liu, Wen-Tso; Lee, Bee Wah

2017-01-01

Gut microbiota play an important role in human immunological processes, potentially affecting allergic diseases such as eczema. The diversity and structure of gut microbiota in infants with eczema have been previously documented. This study aims to evaluate by comparative metagenomics differences in genetic content in gut microbiota of infants with eczema and their matched controls. Stools were collected at the age of one month old from twelve infants from an at risk birth cohort in a case control manner. Clinical follow up for atopic outcomes were carried out at the age of 12 and 24 months. Microbial genomic DNA were extracted from stool samples and used for shotgun sequencing. Comparative metagenomic analysis showed that immune-regulatory TCAAGCTTGA motifs were significantly enriched in the six healthy controls (C) communities compared to the six eczema subjects (E), with many encoded by Bifidobacterium (38% of the total motifs in the C communities). Draft genomes of five Bifidobacterium species populations (B. longum, B. bifidum, B. breve, B. dentium, and B. pseudocatenulatum) were recovered from metagenomic datasets. The B. longum BFN-121-2 genome encoded more TCAAGCTTGA motifs (4.2 copies per one million genome sequence) than other Bifidobacterium genomes. Additionally, the communities in the stool of controls (C) were also significantly enriched in functions associated with tetrapyrrole biosynthesis compared to those of eczema (E). Our results show distinct immune-modulatory genomic properties of gut microbiota in infants associated with eczema and provide new insights into potential role of gut microbiota in affecting human immune homeostasis.

Immune-modulatory genomic properties differentiate gut microbiota of infants with and without eczema

PubMed Central

Oh, Seungdae; Yap, Gaik Chin; Hong, Pei-Ying; Huang, Chiung-Hui; Aw, Marion M.; Shek, Lynette Pei-Chi; Liu, Wen-Tso; Lee, Bee Wah

2017-01-01

Gut microbiota play an important role in human immunological processes, potentially affecting allergic diseases such as eczema. The diversity and structure of gut microbiota in infants with eczema have been previously documented. This study aims to evaluate by comparative metagenomics differences in genetic content in gut microbiota of infants with eczema and their matched controls. Stools were collected at the age of one month old from twelve infants from an at risk birth cohort in a case control manner. Clinical follow up for atopic outcomes were carried out at the age of 12 and 24 months. Microbial genomic DNA were extracted from stool samples and used for shotgun sequencing. Comparative metagenomic analysis showed that immune-regulatory TCAAGCTTGA motifs were significantly enriched in the six healthy controls (C) communities compared to the six eczema subjects (E), with many encoded by Bifidobacterium (38% of the total motifs in the C communities). Draft genomes of five Bifidobacterium species populations (B. longum, B. bifidum, B. breve, B. dentium, and B. pseudocatenulatum) were recovered from metagenomic datasets. The B. longum BFN-121-2 genome encoded more TCAAGCTTGA motifs (4.2 copies per one million genome sequence) than other Bifidobacterium genomes. Additionally, the communities in the stool of controls (C) were also significantly enriched in functions associated with tetrapyrrole biosynthesis compared to those of eczema (E). Our results show distinct immune-modulatory genomic properties of gut microbiota in infants associated with eczema and provide new insights into potential role of gut microbiota in affecting human immune homeostasis. PMID:29049378

The gut microbiota, obesity and insulin resistance

USDA-ARS?s Scientific Manuscript database

The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflam...

The earthworm gut: an ideal habitat for ingested N2O-producing microorganisms.

PubMed

Horn, Marcus A; Schramm, Andreas; Drake, Harold L

2003-03-01

The in vivo production of nitrous oxide (N(2)O) by earthworms is due to their gut microbiota, and it is hypothesized that the microenvironment of the gut activates ingested N(2)O-producing soil bacteria. In situ measurement of N(2)O and O(2) with microsensors demonstrated that the earthworm gut is anoxic and the site of N(2)O production. The gut had a pH of 6.9 and an average water content of approximately 50%. The water content within the gut decreased from the anterior end to the posterior end. In contrast, the concentration of N(2)O increased from the anterior end to the mid-gut region and then decreased along the posterior part of the gut. Compared to the soil in which worms lived and fed, the gut of the earthworm was highly enriched in total carbon, organic carbon, and total nitrogen and had a C/N ratio of 7 (compared to a C/N ratio of 12 in soil). The aqueous phase of gut contents contained up to 80 mM glucose and numerous compounds that were indicative of anaerobic metabolism, including up to 9 mM formate, 8 mM acetate, 3 mM lactate, and 2 mM succinate. Compared to the soil contents, nitrite and ammonium were enriched in the gut up to 10- and 100-fold, respectively. The production of N(2)O by soil was induced when the gut environment was simulated in anoxic microcosms for 24 h (the approximate time for passage of soil through the earthworm). Anoxia, high osmolarity, nitrite, and nitrate were the dominant factors that stimulated the production of N(2)O. Supplemental organic carbon had a very minimal stimulatory effect on the production of N(2)O, and addition of buffer or ammonium had essentially no effect on the initial N(2)O production rates. However, a combination of supplements yielded rates greater than that obtained mathematically for single supplements, suggesting that the maximum rates observed were due to synergistic effects of supplements. Collectively, these results indicate that the special microenvironment of the earthworm gut is ideally suited

Enteric pathogens and gut function: Role of cytokines and STATs.

PubMed

Shea-Donohue, Terez; Fasano, Alessio; Smith, Allen; Zhao, Aiping

2010-09-01

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against the pathogens. In response to the invasion of various pathogens, naïve CD4(+) cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of JAK-STAT signaling pathway and influence gut function by upregulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles.

Enteric pathogens and gut function: Role of cytokines and STATs

PubMed Central

Fasano, Alessio; Smith, Allen; Zhao, Aiping

2010-01-01

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against the pathogens. In response to the invasion of various pathogens, naïve CD4+ cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of JAK-STAT signaling pathway and influence gut function by upregulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles. PMID:21327040

Gut emotions - mechanisms of action of probiotics as novel therapeutic targets for depression and anxiety disorders.

PubMed

Slyepchenko, Anastasiya; Carvalho, Andre F; Cha, Danielle S; Kasper, Siegfried; McIntyre, Roger S

2014-01-01

A priority clinical and research agenda in mood and anxiety disorders is to identify determinants that influence illness trajectory and outcome. Over the past decade, studies have demonstrated a bidirectional relationship between the gut microbiome and brain function (i.e., the microbiota-gut-brain axis). Probiotic treatments and developmental analysis of the microbiome may provide potential treatments and preventative measures for depressive and anxiety disorders. This systematic literature review aims to identify original studies linking the gut microbiota to major depressive disorder and anxiety disorders. Furthermore, this review searched for original reports focusing on possible therapeutic and preventative effects of probiotics for these debilitating conditions. Accumulating data indicate that the gut microbiota communicates with the CNS through neural, endocrine and immune pathways. Studies in germ-free animals indicate that the microbiota is involved in the regulation of the stress response (e.g., hypothalamic-pituitary-adrenal axis) and in CNS development at critical stages. Probiotics attenuate anxiety and depressive-like behaviors in experimental animal models. Notwithstanding some inconsistencies and methodological limitations across trials, clinical studies suggest that probiotics may mitigate anxiety symptoms. However, future studies should investigate the anxiolytic and antidepressant effects of probiotics in more phenotypically homogeneous populations. In conclusion, the emerging concept of a gut microbiota-brain axis suggests that the modulation of the gut microbiota may provide a novel therapeutic target for the treatment and/or prevention of mood and anxiety disorders.

A Mesocosm of Lactobacillus johnsonii, Bifidobacterium longum, and Escherichia coli in the mouse gut.

PubMed

Denou, Emmanuel; Rezzonico, Enea; Panoff, Jean-Michel; Arigoni, Fabrizio; Brüssow, Harald

2009-08-01

The relative contribution of competition and cooperation at the microbe-microbe level is not well understood for the bacteria constituting the gut microbiota. The high number and variability of human gut commensals have hampered the analysis. To get some insight into the question how so many different bacterial species can coexist in the mammalian gut, we studied the interaction between three human gut commensals (Escherichia coli K-12, Lactobacillus johnsonii NCC533, and Bifidobacterium longum NCC2705) in the intestine of gnotobiotic mice. The bacterial titers and their anatomical distribution were studied in the colonized mice. L. johnsonii achieved the highest cell counts in the stomach, while B. longum dominated the colon. The colon was also the intestinal location in which B. longum displayed the highest number of expressed genes, followed by the cecum and the small intestine. Addition of further bacterial strains led to strikingly different results. A Lactobacillus paracasei strain coexisted, while a second B. longum strain was excluded from the system. Notably, this strain lacked an operon involved in the degradation, import, and metabolism of mannosylated glycans. Subsequent introduction of the E. coli Nissle strain resulted in the elimination of L. johnsonii NCC533 and E. coli K-12, while B. longum NCC2705 showed a transient decrease in population size, demonstrating the dynamic nature of microbe-microbe interactions. The study of such simple interacting bacterial systems might help to derive some basic rules governing microbial ecology within the mammalian gut.

Brain-gut-microbiota axis in Parkinson's disease.

PubMed

Mulak, Agata; Bonaz, Bruno

2015-10-07

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.

The liver-gut microbiota axis modulates hepatotoxicity of tacrine in the rat.

PubMed

Yip, Lian Yee; Aw, Chiu Cheong; Lee, Sze Han; Hong, Yi Shuen; Ku, Han Chen; Xu, Winston Hecheng; Chan, Jessalyn Mei Xuan; Cheong, Eleanor Jing Yi; Chng, Kern Rei; Ng, Amanda Hui Qi; Nagarajan, Niranjan; Mahendran, Ratha; Lee, Yuan Kun; Browne, Edward R; Chan, Eric Chun Yong

2018-01-01

The gut microbiota possesses diverse metabolic activities, but its contribution toward heterogeneous toxicological responses is poorly understood. In this study, we investigated the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics, and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variations in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g., Lactobacillus, Bacteroides, and Enterobacteriaceae) and approximately 9% higher β-glucuronidase gene abundance compared with nonresponders. In the validation study, coadministration with oral β-glucuronidase derived from Escherichia coli and pretreatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. This study establishes pertinent gut microbial influences in modifying the hepatotoxicity of tacrine, providing insights for personalized medicine initiatives. (Hepatology 2018;67:282-295). © 2017 by the American Association for the Study of Liver Diseases.

Mycotoxin: Its Impact on Gut Health and Microbiota

PubMed Central

Liew, Winnie-Pui-Pui; Mohd-Redzwan, Sabran

2018-01-01

The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and

Differences in gut microbiota associated with age, sex, and stool consistency in healthy Japanese subjects.

PubMed

Takagi, Tomohisa; Naito, Yuji; Inoue, Ryo; Kashiwagi, Saori; Uchiyama, Kazuhiko; Mizushima, Katsura; Tsuchiya, Saeko; Dohi, Osamu; Yoshida, Naohisa; Kamada, Kazuhiro; Ishikawa, Takeshi; Handa, Osamu; Konishi, Hideyuki; Okuda, Kayo; Tsujimoto, Yoshimasa; Ohnogi, Hiromu; Itoh, Yoshito

2018-06-20

Human gut microbiota is involved in host health and disease development. Investigations of age-related and sex-related alterations in gut microbiota are limited, and the association between stool consistency and gut microbiota has not been fully investigated. We investigated gut microbiota differences related to age, sex, and stool consistency in healthy Japanese subjects. Two-hundred and seventy-seven healthy Japanese subjects aged 20-89 years were enrolled. Fecal samples were obtained to analyze the gut microbiome. We evaluated the association between stool consistency [Bristol stool scale (BSS)] and gut microbiota. Although there were significant differences in the microbial structure between males and females, the α-diversity of gut microbiota showed no difference between males and females or among age groups. There were significant increases in genera Prevotella, Megamonas, Fusobacterium, and Megasphaera and Bifidobacterium, Ruminococcus, and Akkermansia in males and females, respectively. The ratio of hard stools (BSS types 1 and 2) was higher in females; the ratio of loose stools (BSS type 6) was higher in males. No younger male had BSS type 1 or type 2. Fusobacterium in males was significantly higher in the loose consistency group, and Oscillospira was significantly higher in the hard consistency group in males; Campylobacter, SMB53, and Turicibacter were significantly higher in the hard consistency group in females. Several changes in gut microbiota were associated with age and sex. Stool consistency and gut microbiota associations emphasized the importance of stool consistency assessments to understand intestinal function.

Gut Microbiota-Induced Immunoglobulin G Controls Systemic Infection by Symbiotic Bacteria and Pathogens

PubMed Central

Zeng, Melody Y.; Cisalpino, Daniel; Varadarajan, Saranyaraajan; Hellman, Judith; Warren, H. Shaw; Cascalho, Marilia; Inohara, Naohiro; Núñez, Gabriel

2016-01-01

The gut microbiota is compartmentalized in the intestinal lumen and induces local immune responses, but it remains unknown whether the gut microbiota can induce systemic response and contribute to systemic immunity. We report that selective gut symbiotic gram-negative bacteria were able to disseminate systemically to induce immunoglobulin G (IgG) response, which primarily targeted gram-negative bacterial antigens and conferred protection against systemic infections by E. coli and Salmonella by directly coating bacteria to promote killing by phagocytes. T cells and Toll-like receptor 4 on B cells were important in the generation of microbiota-specific IgG. We identified murein lipoprotein (MLP), a highly conserved gram-negative outer membrane protein, as a major antigen that induced systemic IgG homeostatically in both mice and humans. Administration of anti-MLP IgG conferred crucial protection against systemic Salmonella infection. Thus, our findings reveal an important function for the gut microbiota in combating systemic infection through the induction of protective IgG. PMID:26944199

Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus.

PubMed

Su, Xiaomin; Yan, Hui; Huang, Yugang; Yun, Huan; Zeng, Benhua; Wang, Enlin; Liu, Yu; Zhang, Yuan; Liu, Feifei; Che, Yongzhe; Zhang, Zhiqian; Yang, Rongcun

2015-12-21

We here found that intestinal epithelial Paneth cells secrete FABP4, adipsin and adiponectin in both mice and human. Deletion of Paneth cell results in the decrease of FABP4, adipsin and adiponectin not only in intestinal crypt cells but also in sera, suggesting that they may influence the state of the whole body. We also demonstrate that expression of FABP4, adipsin and adiponectin may be modulated by specific gut microbiota. In germ-free (GF) mice, the expression of FABP4, adipsin and adiponectin were lower or difficult to be detected. Feces transplantation promoted the expression of FABP4, adipsin and adiponectin in gut epithelial Paneth cells. We have found that Lactobacillus NK6 colony, which has the highest similarity with Lactobacillus taiwanensis strain BCRC 17755, may induce the expression of FABP4, adipsin and adiponectin through TRAF2 and TRAF6 ubiquitination mediated NF-κB signaling. Taken together, our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells.

Expression of FABP4, adipsin and adiponectin in Paneth cells is modulated by gut Lactobacillus

PubMed Central

Su, Xiaomin; Yan, Hui; Huang, Yugang; Yun, Huan; Zeng, Benhua; Wang, Enlin; Liu, Yu; Zhang, Yuan; Liu, Feifei; Che, Yongzhe; Zhang, Zhiqian; Yang, Rongcun

2015-01-01

We here found that intestinal epithelial Paneth cells secrete FABP4, adipsin and adiponectin in both mice and human. Deletion of Paneth cell results in the decrease of FABP4, adipsin and adiponectin not only in intestinal crypt cells but also in sera, suggesting that they may influence the state of the whole body. We also demonstrate that expression of FABP4, adipsin and adiponectin may be modulated by specific gut microbiota. In germ-free (GF) mice, the expression of FABP4, adipsin and adiponectin were lower or difficult to be detected. Feces transplantation promoted the expression of FABP4, adipsin and adiponectin in gut epithelial Paneth cells. We have found that Lactobacillus NK6 colony, which has the highest similarity with Lactobacillus taiwanensis strain BCRC 17755, may induce the expression of FABP4, adipsin and adiponectin through TRAF2 and TRAF6 ubiquitination mediated NF-κB signaling. Taken together, our findings set up a novel mechanism for FABP4, adipsin and adiponectin through gut microbiota mediating expression in gut Paneth cells. PMID:26687459

Cellulose digestion in primitive hexapods: Effect of ingested antibiotics on gut microbial populations and gut cellulase levels in the firebrat,Thermobia domestica (Zygentoma, Lepismatidae).

PubMed

Treves, D S; Martin, M M

1994-08-01

Antibiotic feeding studies were conducted on the firebrat,Thermobia domestica (Zygentoma, Lepismatidae) to determine if the insect's gut cellulases were of insect or microbial origin. Firebrats were fed diets containing either nystatin, metronidazole, streptomycin, tetracycline, or an antibiotic cocktail consisting of all four antibiotics, and then their gut microbial populations and gut cellulase levels were monitored and compared with the gut microbial populations and gut cellulase levels in firebrats feeding on antibiotic-free diets. Each antibiotic significantly reduced the firebrat's gut micro-flora. Nystatin reduced the firebrat's viable gut fungi by 89%. Tetracycline and the antibiotic cocktail reduced the firebrat's viable gut bacteria by 81% and 67%, respectively, and metronidazole, streptomycin, tetracycline, and the antibiotic cocktail reduced the firebrat's total gut flora by 35%, 32%, 55%, and 64%, respectively. Although antibiotics significantly reduced the firebrat's viable and total gut flora, gut cellulase levels in firebrats fed antibiotics were not significantly different from those in firebrats on an antibiotic-free diet. Furthermore, microbial populations in the firebrat's gut decreased significantly over time, even in firebrats feeding on the antibiotic-free diet, without corresponding decreases in gut cellulase levels. Based on this evidence, we conclude that the gut cellulases of firebrats are of insect origin. This conclusion implies that symbiont-independent cellulose digestion is a primitive trait in insects and that symbiont-mediated cellulose digestion is a derived condition.

High-fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice.

PubMed

Xiao, Liang; Sonne, Si Brask; Feng, Qiang; Chen, Ning; Xia, Zhongkui; Li, Xiaoping; Fang, Zhiwei; Zhang, Dongya; Fjære, Even; Midtbø, Lisa Kolden; Derrien, Muriel; Hugenholtz, Floor; Tang, Longqing; Li, Junhua; Zhang, Jianfeng; Liu, Chuan; Hao, Qin; Vogel, Ulla Birgitte; Mortensen, Alicja; Kleerebezem, Michiel; Licht, Tine Rask; Yang, Huanming; Wang, Jian; Li, Yingrui; Arumugam, Manimozhiyan; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

2017-04-08

It is well known that the microbiota of high-fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent, this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. Using HiSeq-based whole genome sequencing, we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low-fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. HF feeding rather than obesity development led to distinct changes in the gut microbiota. We observed a robust increase in alpha diversity, gene count, abundance of genera known to be butyrate producers, and abundance of genes involved in butyrate production in Sv129 mice compared to BL6 mice fed either a LF or a HF diet. Conversely, the abundance of genes involved in propionate metabolism, associated with increased energy harvest, was higher in BL6 mice than Sv129 mice. The changes in the composition of the gut microbiota were predominantly driven by high-fat feeding rather than reflecting the obese state of the mice. Differences in the abundance of butyrate and propionate producing bacteria in the gut may at least in part contribute to the observed differences in obesity propensity in Sv129 and BL6 mice.

No-scale SU( 5) super-GUTs

DOE PAGES

Ellis, John; Evans, Jason L.; Nagata, Natsumi; ...

2017-04-12

We reconsider the minimal SU( 5) grand unified theory (GUT) in the context of no-scale supergravity inspired by string compactification scenarios, assuming that the soft supersymmetry-breaking parameters satisfy universality conditions at some input scale M in above the GUT scale M GUT. When setting up such a no-scale super-GUT model, special attention must be paid to avoiding the Scylla of rapid proton decay and the Charybdis of an excessive density of cold dark matter, while also having an acceptable mass for the Higgs boson. Furthermore, we do not find consistent solutions if none of the matter and Higgs fields aremore » assigned to twisted chiral supermultiplets, even in the presence of Giudice–Masiero terms. But, consistent solutions may be found if at least one fiveplet of GUT Higgs fields is assigned to a twisted chiral supermultiplet, with a suitable choice of modular weights. Spin-independent dark matter scattering may be detectable in some of these consistent solutions.« less

Impaired gut contractility following hemorrhagic shock is accompaied by IL-6 and G-CSF production and neutrophil infiltration.

PubMed

Hierholzer, C; Kalff, J C; Chakraborty, A; Watkins, S C; Billiar, T R; Bauer, A J; Tweardy, D J

2001-02-01

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment

PubMed Central

Wang, Lin; Li, Peicheng; Tang, Zhaosheng; Yan, Xinfeng; Feng, Bo

2016-01-01

The mechanisms underlying the weight-loss effect of GLP-1 receptor agonists need further elucidation. The present study was performed to explore the effects of liraglutide and saxagliptin on the composition of the gut microbiota. Mice were randomly treated with saxagliptin or liraglutide for eight weeks. Their metabolic profiles were assessed, and 454 pyrosequencing of 16s rRNA of faeces was performed. Liraglutide induced a smaller body weight gain in mice. The pyrosequencing showed that liraglutide, but not saxagliptin, substantially changed the overall structure of the gut microbiota as well as the relative abundance of weight-relevant phylotypes. Subsequent ridge regression analyses indicated that, in addition to food intake (β = −0.182, p = 0.043 in phylotypes inversely correlated with body weight) and blood glucose level (β = −0.240, p = 0.039 in phylotypes positively correlated with body weight), the administration of liraglutide was another independent factor associated with the abundance of weight-relevant phylotypes (β = 0.389, p = 6.24e-5 in inversely correlated ones; β = −0.508, p = 2.25e-5 in positively correlated ones). These results evidenced that GLP-1 receptor agonist liraglutide could modulate the composition of the gut microbiota, leading to a more lean-related profile that was consistent with its weight-losing effect. PMID:27633081

Interindividual variability of soil arsenic metabolism by human gut microbiota using SHIME model.

PubMed

Yin, Naiyi; Du, Huili; Wang, Pengfei; Cai, Xiaolin; Chen, Peng; Sun, Guoxin; Cui, Yanshan

2017-10-01

Arsenic (As) metabolism by human gut microbiota has been evidenced with in vitro experiments from contaminated soils. In this study, the variability in the metabolic potency toward As-contaminated soils and gut microbial diversity were investigated between healthy individuals (Adult versus Child). Arsenic bioaccessibility in the colon phase increased by 1.4-6.8 and 1.2-8.7 folds for adult and child, respectively. We found a high degree of As methylation for the colon digests of the adult (mean 2 μg methylarsenicals/hr/g biomass), 3-folds higher than that of the child. Besides, arsenite [As(III)] concentration (1.5-391.3 μg/L) for the child was 2-18 times for the adult. 16S rRNA gene sequencing revealed that human gut microbiota from 20 various genera potentially had resistance genes to reduce and methylate As under conservative statistics. Our results indicated that As metabolism by gut microbiota from adult and child was significantly different. The adult gut microbiota had a great ability of As methylation; the child gut microbiota exhibited high As(III) level, which could encounter high health risk. The identity and activity of arsenic-metabolizing bacteria isolated from human gut and its homologous role in As metabolism need be further explored. This study provides a better understanding of health risk assessment to adults and children upon soil As exposures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drug-Gut Microbiota Interactions: Implications for Neuropharmacology.

PubMed

Walsh, Jacinta; Griffin, Brendan T; Clarke, Gerard; Hyland, Niall P

2018-05-21

The fate and activity of drugs are frequently dictated not only by the host per se but also by the microorganisms present in the gastrointestinal tract. The gut microbiome is known to, both directly and indirectly, affect drug metabolism. More evidence now hints at the impact that drugs can have on the function and composition of the gut microbiome. Both microbiota-mediated alterations in drug metabolism and drug-mediated alterations in the gut microbiome can have beneficial or detrimental effects on the host. Greater insights into the mechanisms driving these reciprocal drug-gut microbiota interactions are needed, to guide the development of microbiome-targeted dietary or pharmacological interventions, with the potential to enhance drug efficacy or reduce drug side-effects. In this review, we explore the relationship between drugs and the gut microbiome, with a specific focus on potential mechanisms underpinning the drug-mediated alterations on the gut microbiome and the potential implications for psychoactive drugs. This article is protected by copyright. All rights reserved.

Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

PubMed

Quigley, Eamonn M M

2017-10-17

The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

Microbiota-gut-brain axis and the central nervous system.

PubMed

Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

2017-08-08

The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

A geographically-diverse collection of 418 human gut microbiome pathway genome databases

PubMed Central

Hahn, Aria S.; Altman, Tomer; Konwar, Kishori M.; Hanson, Niels W.; Kim, Dongjae; Relman, David A.; Dill, David L.; Hallam, Steven J.

2017-01-01

Advances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GutCyc, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using MetaPathways, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GutCyc data products are searchable online, or may be downloaded and explored locally using MetaPathways and Pathway Tools. PMID:28398290

Gut Microbiota of Nonalcoholic Fatty Liver Disease.

PubMed

Abdou, Reham M; Zhu, Lixin; Baker, Robert D; Baker, Susan S

2016-05-01

The prevalence of nonalcoholic fatty liver disease has been rapidly increasing worldwide. It has become a leading cause of liver transplantation. Accumulating evidence suggests a significant role for gut microbiota in its development and progression. Here we review the effect of gut microbiota on developing hepatic fatty infiltration and its progression. Current literature supports a possible role for gut microbiota in the development of liver steatosis, inflammation and fibrosis. We also review the literature on possible interventions for NAFLD that target the gut microbiota.

The Gut Microbiota and Autism Spectrum Disorders

PubMed Central

Li, Qinrui; Han, Ying; Dy, Angel Belle C.; Hagerman, Randi J.

2017-01-01

Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD. PMID:28503135

The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

PubMed

West, Christina E; Renz, Harald; Jenmalm, Maria C; Kozyrskyj, Anita L; Allen, Katrina J; Vuillermin, Peter; Prescott, Susan L

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Associations between micronutrient intakes and gut microbiota in a group of adults with cystic fibrosis.

PubMed

Li, Li; Krause, Lutz; Somerset, Shawn

2017-08-01

Cystic fibrosis (CF) involves chronic inflammation and oxidative stress affecting mainly the respiratory and digestive systems. Survival rates for CF have improved with advances in treatment including nutritional interventions such as micronutrient supplementation. Diet can modulate gut microbiota in the general population with consequences on local and systemic immunity, and inflammation. The gut microbiota appears disrupted and may associate with pulmonary status in CF. This study investigated associations between micronutrient intakes and gut microbiota variations in a group of adults with CF. Faecal microbiota of sixteen free-living adults with CF was profiled by 16ss rDNA sequencing on the GS-FLX platform. Associations were tested between UniFrac distances of faecal microbiota and time-corresponding micronutrient intakes. Associations between relative abundances of bacterial taxa and micronutrient intakes (those showing significant associations with UniFrac distances) were examined by Spearman correlation. Unweighted UniFrac distances were associated with intakes of potassium and antioxidant vitamins C, E and beta-carotene equivalents, whereas weighted UniFrac distances were associated with antioxidant vitamins riboflavin, niacin equivalents, beta-carotene equivalents and vitamin A equivalents. Intakes of beta-carotene equivalents, vitamin C, vitamin E, niacin equivalents and riboflavin correlated negatively with Bacteroides and/or its corresponding higher level taxa. Intakes of beta-carotene equivalents and vitamin E also positively correlated with Firmicutes and specific taxa belonging to Firmicutes. Some micronutrients, particularly antioxidant vitamins, correlated with gut microbiota variations in the studied cohort. Further research is required to clarify whether antioxidant vitamin intakes can influence CF gut microbiota and potential clinical/therapeutic implications in CF. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and

Pyrosequencing Reveals the Predominance of Pseudomonadaceae in Gut Microbiome of a Gall Midge

PubMed Central

Bansal, Raman; Hulbert, Scot H.; Reese, John C.; Whitworth, Robert J.; Stuart, Jeffrey J.; Chen, Ming-Shun

2014-01-01

Gut microbes are known to play various roles in insects such as digestion of inaccessible nutrients, synthesis of deficient amino acids, and interaction with ecological environments, including host plants. Here, we analyzed the gut microbiome in Hessian fly, a serious pest of wheat. A total of 3,654 high quality sequences of the V3 hypervariable region of the 16S rRNA gene were obtained through 454-pyrosequencing. From these sequences, 311 operational taxonomic units (OTUs) were obtained at the ≥97% similarity cutoff. In the gut of 1st instar, otu01, a member of Pseudomonas, was predominant, representing 90.2% of total sequences. otu13, an unidentified genus in the Pseudomonadaceae family, represented 1.9% of total sequences. The remaining OTUs were each less than 1%. In the gut of the 2nd instar, otu01 and otu13 decreased to 85.5% and 1.5%, respectively. otu04, a member of Buttiauxella, represented 9.7% of total sequences. The remaining OTUs were each less than 1%. In the gut of the 3rd instar, otu01 and otu13 further decreased to 29.0% and 0%, respectively. otu06, otu08, and otu16, also three members of the Pseudomonadaceae family were 13.2%, 8.6%, and 2.3%, respectively. In addition, otu04 and otu14, two members of the Enterobacteriaceae family, were 4.7% and 2.5%; otu18 and otu20, two members of the Xanthomonadaceae family, were 1.3% and 1.2%, respectively; otu12, a member of Achromobacter, was 4.2%; otu19, a member of Undibacterium, was 1.4%; and otu9, otu10, and otu15, members of various families, were 6.1%, 6.3%, and 1.9%, respectively. The investigation into dynamics of Pseudomonas, the most abundant genera, revealed that its population level was at peak in freshly hatched or 1 day larvae as well as in later developmental stages, thus suggesting a prominent role for this bacterium in Hessian fly development and in its interaction with host plants. This study is the first comprehensive survey on bacteria associated with the gut of a gall midge, and

Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease.

PubMed

Mohan, Mahesh; Chow, Cheryl-Emiliane T; Ryan, Caitlin N; Chan, Luisa S; Dufour, Jason; Aye, Pyone P; Blanchard, James; Moehs, Charles P; Sestak, Karol

2016-10-28

The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity ( p < 0.05) following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae ) were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity) of gut microbiome in GS macaques started to change ( p = 0.011) towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b) were upregulated ( p < 0.05) in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911), Prevotella stercorea (NR_041364) and Streptococcus luteciae (AJ297218) that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes in

[Gut microbiota: Description, role and pathophysiologic implications].

PubMed

Landman, C; Quévrain, E

2016-06-01

The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION

PubMed Central

Yang, Tao; Santisteban, Monica M.; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J.; Raizada, Mohan K.; Mohamadzadeh, Mansour

2015-01-01

Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. The present study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension since genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of two rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes to Bacteroidetes ratio. These changes were accompanied with decreases in acetate- and butyrate-producing bacteria. Additionally, the microbiota of a small cohort of human hypertension patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes to Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes to Bacteroidetes ratio. These observations demonstrate that high BP is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

PubMed

Ntranos, Achilles; Casaccia, Patrizia

2018-01-01

Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

Gut-Bioreactor and Human Health in Future.

PubMed

Purohit, Hemant J

2018-03-01

Gut-microbiome provides the complementary metabolic potential to the human system. To understand the active participation and the performance of the microbial community in human health, the concept of gut as a plug-flow reactor with the fed-batch mode of operation can provide better insight. The concept suggests the virtual compartmentalized gut with sequential stratification of the microbial community in response to a typical host genotype. It also provides the analysis plan for gut microbiome; and its relevance in developing health management options under the identified clinical conditions.

Villification of the gut

NASA Astrophysics Data System (ADS)

Tallinen, Tuomas; Shyer, Amy E.; Tabin, Clifford J.; Mahadevan, L.

2014-03-01

The villi of the human and chick gut are formed in similar stepwise progressions, wherein the mesenchyme and attached epithelium first fold into longitudinal ridges, then a zigzag pattern, and lastly individual villi. We combine biological manipulations and quantitative modeling to show that these steps of villification depend on the sequential differentiation of the distinct smooth muscle layers of the gut, which restrict the expansion of the growing endoderm and mesenchyme, generating compressive stresses that lead to their buckling and folding. Our computational model incorporates measured elastic properties and growth rates in the developing gut, recapitulating the morphological patterns seen during villification in a variety of species. Our study provides a mechanical basis for the genesis of these epithelial protrusions that are essential for providing sufficient surface area for nutrient absorption.

Gut fermentation seems to promote decompression sickness in humans.

PubMed

de Maistre, Sébastien; Vallee, Nicolas; Gempp, Emmanuel; Louge, Pierre; Duchamp, Claude; Blatteau, Jean-Eric

2016-10-01

Massive bubble formation after diving can lead to decompression sickness (DCS) that can result in neurological disorders. In experimental dives using hydrogen as the diluent gas, decreasing the body's H 2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. In contrast, we have shown that gut bacterial fermentation in rats on a standard diet promotes DCS through endogenous hydrogen production. Therefore, we set out to test these experimental results in humans. Thirty-nine divers admitted into our hyperbaric center with neurological DCS (Affected Divers) were compared with 39 healthy divers (Unaffected Divers). Their last meal time and composition were recorded. Gut fermentation rate was estimated by measuring breath hydrogen 1-4 h after the dive. Breath hydrogen concentrations were significantly higher in Affected Divers (15 ppm [6-23] vs. 7 ppm [3-12]; P = 0.0078). With the use of a threshold value of 16.5 ppm, specificity was 87% [95% confidence interval (CI) 73-95] for association with neurological DCS onset. We observed a strong association between hydrogen values above this threshold and an accident occurrence (odds ratio = 5.3, 95% CI 1.8-15.7, P = 0.0025). However, high fermentation potential foodstuffs consumption was not different between Affected and Unaffected Divers. Gut fermentation rate at dive time seemed to be higher in Affected Divers. Hydrogen generated by fermentation diffuses throughout the body and could increase DCS risk. Prevention could be helped by excluding divers who are showing a high fermentation rate, by eliminating gas produced in gut, or even by modifying intestinal microbiota to reduce fermentation rate during a dive. Copyright © 2016 the American Physiological Society.

Diet simplification selects for high gut microbial diversity and strong fermenting ability in high-altitude pikas.

PubMed

Li, Huan; Qu, Jiapeng; Li, Tongtong; Wirth, Stephan; Zhang, Yanming; Zhao, Xinquan; Li, Xiangzhen

2018-06-03

The gut microbiota in mammals plays a key role in host metabolism and adaptation. However, relatively little is known regarding to how the animals adapts to extreme environments through regulating gut microbial diversity and function. Here, we investigated the diet, gut microbiota, short-chain fatty acid (SCFA) profiles, and cellulolytic activity from two common pika (Ochotona spp.) species in China, including Plateau pika (Ochotona curzoniae) from the Qinghai-Tibet Plateau and Daurian pika (Ochotona daurica) from the Inner Mongolia Grassland. Despite a partial diet overlap, Plateau pikas harbored lower diet diversity than Daurian pikas. Some bacteria (e.g., Prevotella and Ruminococcus) associated with fiber degradation were enriched in Plateau pikas. They harbored higher gut microbial diversity, total SCFA concentration, and cellulolytic activity than Daurian pikas. Interestingly, cellulolytic activity was positively correlated with the gut microbial diversity and SCFAs. Gut microbial communities and SCFA profiles were segregated structurally between host species. PICRUSt metagenome predictions demonstrated that microbial genes involved in carbohydrate metabolism and energy metabolism were overrepresented in the gut microbiota of Plateau pikas. Our results demonstrate that Plateau pikas harbor a stronger fermenting ability for the plant-based diet than Daurian pikas via gut microbial fermentation. The enhanced ability for utilization of plant-based diets in Plateau pikas may be partly a kind of microbiota adaptation for more energy requirements in cold and hypoxic high-altitude environments.

Pregnancy-related changes in the maternal gut microbiota are dependent upon the mother's periconceptional diet

PubMed Central

Gohir, Wajiha; Whelan, Fiona J; Surette, Michael G; Moore, Caroline; Schertzer, Jonathan D; Sloboda, Deborah M

2015-01-01

Shifts in the maternal gut microbiome have been implicated in metabolic adaptations to pregnancy. We investigated how pregnancy and diet interact to influence the composition of the maternal gut microbiota. Female C57BL/6 mice were fed either a control or a high fat diet for 8 weeks prior to mating. After confirmation of pregnancy, maternal weight gain and food intake were recorded. Fecal pellets were collected at 2 timepoints prior to mating (at the beginning of the experiment, and after 6 weeks of the specified diet) and at 4 timepoints during pregnancy (gestation day 0.5, 5.5, 10.5, and 15.5). The microbial composition and predicted metabolic functionality of the non-pregnant and pregnant gut was determined via sequencing of the variable 3 region of the 16S rRNA gene. Upon conception, differences in gut microbial communities were observed in both control and high fat-fed mice, including an increase in mucin-degrading bacteria. Control versus high fat-fed pregnant mice possessed the most profound changes to their maternal gut microbiota as indicated by statistically significant taxonomic differences. High fat-fed pregnant mice, when compared to control-fed animals, were found to be significantly enriched in microbes involved in metabolic pathways favoring fatty acid, ketone, vitamin, and bile synthesis. We show that pregnancy-induced changes in the female gut microbiota occur immediately at the onset of pregnancy, are vulnerable to modulation by diet, but are not dependent upon increases in maternal weight gain during pregnancy. High fat diet intake before and during pregnancy results in distinctive shifts in the pregnant gut microbiota in a gestational-age dependent manner and these shifts predict significant differences in the abundance of genes that favor lipid metabolism, glycolysis and gluconeogenic metabolic pathways over the course of pregnancy. PMID:26322500

Influence of gut microbiota on neuropsychiatric disorders.

PubMed

Cenit, María Carmen; Sanz, Yolanda; Codoñer-Franch, Pilar

2017-08-14

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and

Influence of gut microbiota on neuropsychiatric disorders

PubMed Central

Cenit, María Carmen; Sanz, Yolanda; Codoñer-Franch, Pilar

2017-01-01

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors

Using corticosteroids to reshape the gut microbiome: implications for inflammatory bowel diseases.

PubMed

Huang, Edmond Y; Inoue, Takuya; Leone, Vanessa A; Dalal, Sushila; Touw, Ketrija; Wang, Yunwei; Musch, Mark W; Theriault, Betty; Higuchi, Kazuhide; Donovan, Sharon; Gilbert, Jack; Chang, Eugene B

2015-05-01

Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. We sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Adult male C57Bl/6 mice, germ-free, Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for 4 weeks. Fecal samples were collected for gut microbiota analysis through 16S rRNA terminal restriction fragment length polymorphism and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. Germ-free mice were conventionalized with gut microbes from treated and nontreated groups to determine their functional capacities in recipient hosts. Exposure to dexamethasone in wild-type mice led to substantial shifts in gut microbiota over a 4-week period. Furthermore, a significant downregulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a proinflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pretreated with dexamethasone, however, ameliorated symptoms of inflammation. Commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after glucocorticoid exposure. These findings underscore the notion that intestinal microbes comprise a "microbial organ" essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.

Gut microbiota and host metabolism in liver cirrhosis

PubMed Central

Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

2015-01-01

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

Gut microbiota and host metabolism in liver cirrhosis.

PubMed

Usami, Makoto; Miyoshi, Makoto; Yamashita, Hayato

2015-11-07

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics

The Gut Microbiota of Marine Fish.

PubMed

Egerton, Sian; Culloty, Sarah; Whooley, Jason; Stanton, Catherine; Ross, R Paul

2018-01-01

The body of work relating to the gut microbiota of fish is dwarfed by that on humans and mammals. However, it is a field that has had historical interest and has grown significantly along with the expansion of the aquaculture industry and developments in microbiome research. Research is now moving quickly in this field. Much recent focus has been on nutritional manipulation and modification of the gut microbiota to meet the needs of fish farming, while trying to maintain host health and welfare. However, the diversity amongst fish means that baseline data from wild fish and a clear understanding of the role that specific gut microbiota play is still lacking. We review here the factors shaping marine fish gut microbiota and highlight gaps in the research.

Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice.

PubMed

Singh, Dhirendra Pratap; Singh, Jagdeep; Boparai, Ravneet Kaur; Zhu, JianHua; Mantri, Shrikant; Khare, Pragyanshu; Khardori, Romesh; Kondepudi, Kanthi Kiran; Chopra, Kanwaljit; Bishnoi, Mahendra

2017-09-01

High fat diet (HFD)-induced alterations in gut microbiota and resultant 'leaky gut' phenomenon promotes metabolic endotoxemia, ectopic fat deposition, and low-grade systemic inflammation. Here we evaluated the effects of a combination of green tea extract (GTE) with isomalto-oligosaccharide (IMOs) on HFD-induced alterations in mice. Male Swiss albino mice were fed with HFD (58% fat kcal) for 12 weeks. Systemic adiposity, gut derangement parameters and V3-V4 region based 16S rRNA metagenomic sequencing, ectopic fat deposition, liver metabolome analysis, systemic and tissue inflammation, and energy homeostasis markers along with gene expression analysis in multiple tissues were done in mice supplemented with GTE, IMOs or their combination. The combination of GTE and IMOs effectively prevented HFD-induced adiposity and lipid accumulation in liver and muscle while normalizing fasting blood glucose, insulin, glucagon, and leptin levels. Co-administration of GTE with IMOs effectively modulated liver metabolome associated with lipid metabolism. It also prevented leaky gut phenotype and HFD-induced increase in circulating lipopolysaccharides and pro-inflammatory cytokines (e.g. resistin, TNF-α, and IL-1β) and reduction in anti-inflammatory cytokines (e.g. adiponectin and IL-6). Gene expression analysis across multiple tissues further supported these functional outcomes. Most importantly, this combination improved beneficial gut microbiota (Lactobacillus sp., Bifidobacteria, Akkermansia muciniphila, Roseburia spp.) abundances, restored Firmicutes/Bacteriodetes and improved Prevotella/Bacteroides proportions. In particular, a combination of these two agents has shown improved beneficial effects on multiple parameters studied. Data presented herein suggests that strategically chosen food components might be highly effective in the prevention of HFD-induced alterations and may further be developed as functional foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular Insight into Gut Microbiota and Rheumatoid Arthritis.

PubMed

Wu, Xiaohao; He, Bing; Liu, Jin; Feng, Hui; Ma, Yinghui; Li, Defang; Guo, Baosheng; Liang, Chao; Dang, Lei; Wang, Luyao; Tian, Jing; Zhu, Hailong; Xiao, Lianbo; Lu, Cheng; Lu, Aiping; Zhang, Ge

2016-03-22

Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA.

Intersecting branes, Higgs sector, and chirality from N = 4 SYM with soft SUSY breaking

NASA Astrophysics Data System (ADS)

Sperling, Marcus; Steinacker, Harold C.

2018-04-01

We consider SU( N ) N = 4 super Yang-Mills with cubic and quadratic soft SUSY breaking potential, such that the global SU(4) R is broken to SU(3) or further. As shown recently, this set-up supports a rich set of non-trivial vacua with the geometry of self-intersecting SU(3) branes in 6 extra dimensions. The zero modes on these branes can be interpreted as 3 generations of bosonic and chiral fermionic strings connecting the branes at their intersections. Here, we uncover a large class of exact solutions consisting of branes connected by Higgs condensates, leading to Yukawa couplings between the chiral fermionic zero modes. Under certain decoupling conditions, the backreaction of the Higgs on the branes vanishes exactly. The resulting physics is that of a spontaneously broken chiral gauge theory on branes with fluxes. In particular, we identify combined brane plus Higgs configurations which lead to gauge fields that couple to chiral fermions at low energy. This turns out to be quite close to the Standard Model and its constructions via branes in string theory. As a by-product, we construct a G 2-brane solution corresponding to a squashed fuzzy coadjoint orbit of G 2.

Mechanisms of inflammation-driven bacterial dysbiosis in the gut

PubMed Central

Zeng, MY; Inohara, N; Nuñez, G

2018-01-01

The gut microbiota has diverse and essential roles in host metabolism, development of the immune system and as resistance to pathogen colonization. Perturbations of the gut microbiota, termed gut dysbiosis, are commonly observed in diseases involving inflammation in the gut, including inflammatory bowel disease, infection, colorectal cancer and food allergies. Importantly, the inflamed microenvironment in the gut is particularly conducive to blooms of Enterobacteriaceae, which acquire fitness benefits while other families of symbiotic bacteria succumb to environmental changes inflicted by inflammation. Here we summarize studies that examined factors in the inflamed gut that contribute to blooms of Enterobacterieaceae, and highlight potential approaches to restrict Enterobacterial blooms in treating diseases that are otherwise complicated by overgrowth of virulent Enterobacterial species in the gut. PMID:27554295

[Glucose homeostasis and gut-brain connection].

PubMed

De Vadder, Filipe; Mithieux, Gilles

2015-02-01

Since the XIX(th) century, the brain has been known for its role in regulating food intake (via the control of hunger sensation) and glucose homeostasis. Further interest has come from the discovery of gut hormones, which established a clear link between the gut and the brain in regulating glucose and energy homeostasis. The brain has two particular structures, the hypothalamus and the brainstem, which are sensitive to information coming either from peripheral organs or from the gut (via circulating hormones or nutrients) about the nutritional status of the organism. However, the efforts for a better understanding of these mechanisms have allowed to unveil a new gut-brain neural axis as a key regulator of the metabolic status of the organism. Certain nutrients control the hypothalamic homeostatic function via this axis. In this review, we describe how the gut is connected to the brain via different neural pathways, and how the interplay between these two organs drives the energy balance. © 2015 médecine/sciences – Inserm.

Introduction to the human gut microbiota.

PubMed

Thursby, Elizabeth; Juge, Nathalie

2017-05-16

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host-microbe interactions. © 2017 The Author(s).

Introduction to the human gut microbiota

PubMed Central

Thursby, Elizabeth

2017-01-01

The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bacterial composition (dysbiosis) has been associated with the pathogenesis of many inflammatory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions. PMID:28512250

Microbiota-gut-brain axis: Interaction of gut microbes and their metabolites with host epithelial barriers.

PubMed

Bhattarai, Y

2018-06-01

The gastrointestinal barrier and the blood brain barrier represent an important line of defense to protect the underlying structures against harmful external stimuli. These host barriers are composed of epithelial and endothelial cells interconnected by tight junction proteins along with several other supporting structures. Disruption in host barrier structures has therefore been implicated in various diseases of the gastrointestinal tract and the central nervous system. While there are several factors that influence host barrier, recently there is an increasing appreciation of the role of gut microbiota and their metabolites in regulating barrier integrity. In the current issue of Neurogastroenterology and Motility, Marungruang et al. describe the effect of gastrointestinal barrier maturation on gut microbiota and the blood brain barrier adding to the growing evidence of microbiota-barrier interactions. In this mini-review I will discuss the effect of gut microbiota on host epithelial barriers and its implications for diseases associated with disrupted gut-brain axis. © 2018 John Wiley & Sons Ltd.

Characterization of the gut microbiota in the red panda (Ailurus fulgens).

PubMed

Kong, Fanli; Zhao, Jiangchao; Han, Shushu; Zeng, Bo; Yang, Jiandong; Si, Xiaohui; Yang, Benqing; Yang, Mingyao; Xu, Huailiang; Li, Ying

2014-01-01

The red panda is the only living species of the genus Ailurus. Like giant pandas, red pandas are also highly specialized to feed mainly on highly fibrous bamboo. Although several studies have focused on the gut microbiota in the giant panda, little is known about the gut microbiota of the red panda. In this study, we characterized the fecal microbiota from both wild (n = 16) and captive (n = 6) red pandas using a pyrosequecing based approach targeting the V1-V3 hypervariable regions of the 16S rRNA gene. Distinct bacterial communities were observed between the two groups based on both membership and structure. Wild red pandas maintained significantly higher community diversity, richness and evenness than captive red pandas, the communities of which were skewed and dominated by taxa associated with Firmicutes. Phylogenetic analysis of the top 50 OTUs revealed that 10 of them were related to known cellulose degraders. To the best of our knowledge, this is the first study of the gut microbiota of the red panda. Our data suggest that, similar to the giant panda, the gut microbiota in the red panda might also play important roles in the digestion of bamboo.

A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

PubMed

Sylvia, Kristyn E; Demas, Gregory E

2018-03-01

The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder.

PubMed

Coretti, Lorena; Cristiano, Claudia; Florio, Ermanno; Scala, Giovanni; Lama, Adriano; Keller, Simona; Cuomo, Mariella; Russo, Roberto; Pero, Raffaela; Paciello, Orlando; Mattace Raso, Giuseppina; Meli, Rosaria; Cocozza, Sergio; Calignano, Antonio; Chiariotti, Lorenzo; Lembo, Francesca

2017-03-28

Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.

Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials.

PubMed

Piwowarski, Jakub P; Granica, Sebastian; Zwierzyńska, Marta; Stefańska, Joanna; Schopohl, Patrick; Melzig, Matthias F; Kiss, Anna K

2014-08-08

Ellagitannin-rich plant materials are widely used in traditional medicine as effective, internally used anti-inflammatory agents. Due to the not well-established bioavailability of ellagitannins, the mechanisms of observed therapeutic effects following oral administration still remain unclear. The aim of the study was to evaluate if selected ellagitannin-rich plant materials could be the source of bioavailable gut microbiota metabolites, i.e. urolithins, together with determination of the anti-inflammatory activity of the metabolites produced on the THP-1 cell line derived macrophages model. The formation of urolithins was determined by ex vivo incubation of human fecal samples with aqueous extracts from selected plant materials. The anti-inflammatory activity study of metabolites was determined on PMA differentiated, IFN-γ and LPS stimulated, human THP-1 cell line-derived macrophages. The formation of urolithin A, B and C by human gut microbiota was established for aqueous extracts from Filipendula ulmaria (L.) Maxim. herb (Ph. Eur.), Geranium pratense L. herb, Geranium robertianum L. herb, Geum urbanum L. root and rhizome, Lythrum salicaria L. herb (Ph. Eur.), Potentilla anserina L. herb, Potentilla erecta (L.) Raeusch rhizome (Ph. Eur.), Quercus robur L. bark (Ph. Eur.), Rubus idaeus L. leaf, Rubus fruticosus L. and pure ellagitannin vescalagin. Significant inhibition of TNF-α production was determined for all urolithins, while for the most potent urolithin A inhibition was observed at nanomolar concentrations (at 0.625 μM 29.2±6.4% of inhibition). Urolithin C was the only compound inhibiting IL-6 production (at 0.625 μM 13.9±2.2% of inhibition). The data obtained clearly indicate that in the case of peroral use of the examined ellagitannin-rich plant materials the bioactivity of gut microbiota metabolites, i.e. urolithins, has to be taken under consideration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The human gut microbiota and virome: Potential therapeutic implications.

PubMed

Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio

2015-12-01

Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Candida albicans and Enterococcus faecalis in the gut

PubMed Central

Garsin, Danielle A; Lorenz, Michael C

2013-01-01

The fungus Candida albicans and the gram-positive bacterium Enterococcus faecalis are both normal residents of the human gut microbiome and cause opportunistic disseminated infections in immunocompromised individuals. Using a nematode infection model, we recently showed that co-infection resulted in less pathology and less mortality than infection with either species alone and this was partly explained by an interkingdom signaling event in which a bacterial-derived product inhibits hyphal morphogenesis of C. albicans. In this addendum we discuss these findings in the contest of other described bacterial-fungal interactions and recent data suggesting a potentially synergistic relationship between these two species in the mouse gut as well. We suggest that E. faecalis and C. albicans promote a mutually beneficial association with the host, in effect choosing a commensal lifestyle over a pathogenic one. PMID:23941906

Mechanisms Linking the Gut Microbiome and Glucose Metabolism

PubMed Central

Kratz, Mario; Damman, Chris J.; Hullarg, Meredith

2016-01-01

Context: Type 2 diabetes mellitus is associated with gastrointestinal dysbiosis involving both compositional and functional changes in the gut microbiome. Changes in diet and supplementation with probiotics and prebiotics (ie, fermentable fibers) can induce favorable changes in gut bacterial species and improve glucose homeostasis. Objective: This paper will review the data supporting several potential mechanisms whereby gut dysbiosis contributes to metabolic dysfunction, including microbiota driven increases in systemic lipopolysaccharide concentrations, changes in bile acid metabolism, alterations in short chain fatty acid production, alterations in gut hormone secretion, and changes in circulating branched-chain amino acids. Methods: Data for this review were identified by searching English language references from PubMed and relevant articles. Conclusions: Understanding the mechanisms linking the gut microbiome to glucose metabolism, and the relevant compositional and functional characteristics of the gut microbiome, will help direct future research to develop more targeted approaches or novel compounds aimed at restoring a more healthy gut microbiome as a new approach to prevent and treat type 2 diabetes mellitus and related metabolic conditions. PMID:26938201

Microbiota in fermented feed and swine gut.

PubMed

Wang, Cheng; Shi, Changyou; Zhang, Yu; Song, Deguang; Lu, Zeqing; Wang, Yizhen

2018-04-01

Development of alternatives to antibiotic growth promoters (AGP) used in swine production requires a better understanding of their impacts on the gut microbiota. Supplementing fermented feed (FF) in swine diets as a novel nutritional strategy to reduce the use of AGP and feed price, can positively affect the porcine gut microbiota, thereby improving pig productivities. Previous studies have noted the potential effects of FF on the shift in benefit of the swine microbiota in different regions of the gastrointestinal tract (GIT). The positive influences of FF on swine gut microbiota may be due to the beneficial effects of both pre- and probiotics. Necessarily, some methods should be adopted to properly ferment and evaluate the feed and avoid undesired problems. In this mini-review, we mainly discuss the microbiota in both fermented feed and swine gut and how FF influences swine gut microbiota.

Acne vulgaris, probiotics and the gut-brain-skin axis: from anecdote to translational medicine.

PubMed

Bowe, W; Patel, N B; Logan, A C

2014-06-01

Acne vulgaris has long been postulated to feature a gastrointestinal mechanism, dating back 80 years to dermatologists John H. Stokes and Donald M. Pillsbury. They hypothesised that emotional states (e.g. depression and anxiety) could alter normal intestinal microbiota, increase intestinal permeability, and contribute to systemic inflammation. They were also among the first to propose the use of probiotic Lactobacillus acidophilus cultures. In recent years, aspects of this gut-brain-skin theory have been further validated via modern scientific investigations. It is evident that gut microbes and oral probiotics could be linked to the skin, and particularly acne severity, by their ability to influence systemic inflammation, oxidative stress, glycaemic control, tissue lipid content, and even mood. This intricate relationship between gut microbiota and the skin may also be influenced by diet, a current area of intense scrutiny by those who study acne. Here we provide a historical background to the gut-brain-skin theory in acne, followed by a summary of contemporary investigations and clinical implications.

Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury.

PubMed

Cho, Young-Eun; Yu, Li-Rong; Abdelmegeed, Mohamed A; Yoo, Seong-Ho; Song, Byoung-Joon

2018-07-01

Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced gut leakiness. The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses. Binge alcohol exposure caused apoptosis of gut enterocytes with elevated serum endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated proteins and apoptosis-related marker proteins were significantly elevated in binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses of the TJ-enriched fractions of intestinal epithelial layers revealed that several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed rats compared to controls. Consistently, the levels of TJ proteins (claudin-1, claudin-4, occludin and zonula occludens-1), AJ proteins (β-catenin and E-cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats, wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice. Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent proteolysis, resulting in their decreased levels. These results demonstrated for the first time the critical roles of CYP2E1, apoptosis of enterocytes, and nitration followed by ubiquitin-dependent proteolytic degradation of the

The Gut Microbiota of Marine Fish

PubMed Central

Egerton, Sian; Culloty, Sarah; Whooley, Jason; Stanton, Catherine; Ross, R. Paul

2018-01-01

The body of work relating to the gut microbiota of fish is dwarfed by that on humans and mammals. However, it is a field that has had historical interest and has grown significantly along with the expansion of the aquaculture industry and developments in microbiome research. Research is now moving quickly in this field. Much recent focus has been on nutritional manipulation and modification of the gut microbiota to meet the needs of fish farming, while trying to maintain host health and welfare. However, the diversity amongst fish means that baseline data from wild fish and a clear understanding of the role that specific gut microbiota play is still lacking. We review here the factors shaping marine fish gut microbiota and highlight gaps in the research. PMID:29780377

Saccharide breakdown and fermentation by the honey bee gut microbiome.

PubMed

Lee, Fredrick J; Rusch, Douglas B; Stewart, Frank J; Mattila, Heather R; Newton, Irene L G

2015-03-01

The honey bee, the world's most important agricultural pollinator, relies exclusively on plant-derived foods for nutrition. Nectar and pollen collected by honey bees are processed and matured within the nest through the activities of honey bee-derived microbes and enzymes. In order to better understand the contribution of the microbial community to food processing in the honey bee, we generated a metatranscriptome of the honey bee gut microbiome. The function of the microbial community in the honey bee, as revealed by metatranscriptome sequencing, resembles that of other animal guts and food-processing environments. We identified three major bacterial classes that are active in the gut (γ-Proteobacteria, Bacilli and Actinobacteria), all of which are predicted to participate in the breakdown of complex macromolecules (e.g. polysaccharides and polypeptides), the fermentation of component parts of these macromolecules, and the generation of various fermentation products, such as short-chain fatty acids and alcohol. The ability of the microbial community to metabolize these carbon-rich food sources was confirmed through the use of community-level physiological profiling. Collectively, these findings suggest that the gut microflora of the honey bee harbours bacterial members with unique roles, which ultimately can contribute to the processing of plant-derived food for colonies. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Gut Microbiome-based Therapeutics in Liver Cirrhosis: Basic Consideration for the Next Step.

PubMed

Fukui, Hiroshi

2017-09-28

Infections account for significant morbidity and mortality in liver cirrhosis and most are related to the gut microbiome. Fecal dysbiosis, characterized by an overgrowth of potentially pathogenic bacteria and a decrease in autochthonous non-pathogenic bacteria, becomes prominent with the progression of liver cirrhosis. In cirrhotic patients, disruption of the intestinal barrier causes intestinal hyperpermeability (i.e. leaky gut), which is closely related to gut dysmotility, dysbiosis and small intestinal bacterial overgrowth and may induce pathological bacterial translocation. Although the involved microbial taxa are somewhat different between the cirrhotic patients from the East and the West, the common manifestation of a shortage of bacteria that contribute to the production of short-chain fatty acids and secondary bile acids may facilitate intestinal inflammation, leaky gut and gut dysbiosis. Translocated endotoxin and bacterial DNA are capable of provoking potent inflammation and affecting the metabolic and hemodynamic systems, which may ultimately enhance the progression of liver cirrhosis and its various complications, such as hepatic encephalopathy (HE), variceal bleeding, infection and renal disturbances. Among studies on the microbiome-based therapeutics, findings of probiotic effects on HE have been contradictory in spite of several supportive results. However, the effects of synbiotics and prebiotics are substantially documented. The background of their effectiveness should be evaluated again in relation to the cirrhosis-related changes in gut microbiome and their metabolic effects. Strict indications for the antibiotic rifaximin remain unestablished, although its effect is promising, improving HE and other complications with little influence on microbial populations. The final goal of microbiome-based therapeutics is to adjust the gut-liver axis to the maximal benefit of cirrhotic patients, with the aid of evolving metagenomic and metabolomic analyses.

Effect of gut bacterial isolates from Apis mellifera jemenitica on Paenibacillus larvae infected bee larvae.

PubMed

Al-Ghamdi, Ahmad; Ali Khan, Khalid; Javed Ansari, Mohammad; Almasaudi, Saad B; Al-Kahtani, Saad

2018-02-01

The probiotic effects of seven newly isolated gut bacteria, from the indegenous honey bees of Saudi Arabia were investigated. In vivo bioassays were used to investigate the effects of each gut bacterium namely, Fructobacillus fructosus (T1), Proteus mirabilis (T2), Bacillus licheniformis (T3), Lactobacillus kunkeei (T4), Bacillus subtilis (T5), Enterobacter kobei (T6), and Morganella morganii (T7) on mortality percentage of honey bee larvae infected with P. larvae spores along with negative control (normal diet) and positive control (normal diet spiked with P. larvae spores). Addition of gut bacteria to the normal diet significantly reduced the mortality percentage of the treated groups. Mortality percentage in all treated groups ranged from 56.67% up to 86.67%. T6 treated group exhibited the highest mortality (86.67%), whereas T4 group showed the lowest mortality (56.67%). Among the seven gut bacterial treatments, T4 and T3 decreased the mortality 56.67% and 66.67%, respectively, whereas, for T2, T6, and T7 the mortality percentage was equal to that of the positive control (86.67%). Mortality percentages in infected larval groups treated with T1, and T5 were 78.33% and 73.33% respectively. Most of the mortality occurred in the treated larvae during days 2 and 3. Treatments T3 and T4 treatments showed positive effects and reduced mortality.

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota.

PubMed

Milani, Christian; Duranti, Sabrina; Bottacini, Francesca; Casey, Eoghan; Turroni, Francesca; Mahony, Jennifer; Belzer, Clara; Delgado Palacio, Susana; Arboleya Montes, Silvia; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Rodriguez, Juan Miguel; Bode, Lars; de Vos, Willem; Gueimonde, Miguel; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

2017-12-01

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and

The impact of gut microbiota on kidney function and pathogenesis.

PubMed

Mahmoodpoor, Fariba; Rahbar Saadat, Yalda; Barzegari, Abolfazl; Ardalan, Mohammadreza; Zununi Vahed, Sepideh

2017-09-01

Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Human gut microbiota: does diet matter?

PubMed

Maukonen, Johanna; Saarela, Maria

2015-02-01

The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated.

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases.

PubMed

Yarandi, Shadi S; Peterson, Daniel A; Treisman, Glen J; Moran, Timothy H; Pasricha, Pankaj J

2016-04-30

Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes.

PubMed

Clark, Allison; Mach, Núria

2016-01-01

Fatigue, mood disturbances, under performance and gastrointestinal distress are common among athletes during training and competition. The psychosocial and physical demands during intense exercise can initiate a stress response activating the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal (HPA) axes, resulting in the release of stress and catabolic hormones, inflammatory cytokines and microbial molecules. The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function. The gut microbiome and its influence on host behavior, intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis. Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition. For instance, induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus, which have well defined roles in intestinal mucus degradation and immune function. Diet is known to dramatically modulate the composition of the gut microbiota. Due to the considerable complexity of stress responses in elite athletes (from leaky gut to increased catabolism and depression), defining standard diet regimes is difficult. However, some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results, indicating that the microbiota acts like an endocrine organ (e.g. secreting serotonin, dopamine or other neurotransmitters) and may control the HPA axis in athletes. What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality (e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters). As more

Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.

PubMed

Cai, Jingwei; Zhang, Limin; Jones, Richard A; Correll, Jared B; Hatzakis, Emmanuel; Smith, Philip B; Gonzalez, Frank J; Patterson, Andrew D

2016-02-05

Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state.

Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.

Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized withmore » gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.« less

Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

DOE PAGES

Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.; ...

2015-05-01

Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized withmore » gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.« less

An altered gut microbiota in HIV infection: future prospective of FMT therapy.

PubMed

Kang, Yongbo; Cai, Yue

2018-06-07

Human immunodeficiency virus (HIV) infection progressively destroys CD4+ mononuclear cells leading to profound cellular immune deficiency that manifests as life threatening opportunistic infections and malignancies, i.e., the acquired immune deficiency syndrome (AIDS). Gut microbiota play key roles in the modulation of host metabolism and gene expression, maintenance of epithelial integrity, and mediation of inflammatory and immunity. Hence, the normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, a large number of studies have shown that the alteration of the gut microbiota contribute to the pathogenesis of several diseases, such as inflammatory bowel diseases, irritable bowel syndrome, metabolic diseases, anorexia nervosa, autoimmune diseases, multiple sclerosis, cancer, neuropsychiatric disorders, and cardiovascular diseases. Recently, accumulating evidences have has shed light on the association of dysbiosis of gut microbiota with HIV infection. Hence, the modification of gut microbiota may be a potential therapeutic tool. Fecal microbiota transplantation (FMT) may be a more straightforward and better therapy for HIV infection by manipulating the human intestinal bacteria. However, the relevant research is very limited, and large amount of scientific research work need to be done in the near further.

Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides , Odoribacter , and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a

An Investigation of Cellulose Digesting Bacteria in the Panda Gut Microbiome

NASA Astrophysics Data System (ADS)

Lu, M.; Leung, F. C.

2014-12-01

The Giant Panda (Ailuropoda melanoleuca) diet consists primarily of bamboo leaves, stems and shoots. However, the Giant Panda lacks genes for the enzymes needed to digest cellulose, the core component of bamboo. Thus, it is hypothesized that the cellulolytic digestion necessary for maintaining the Giant Panda diet is carried out by microbial symbionts in the panda gut microbiota. Fecal microbiota is used as surrogate index for gut microbiota since the Giant Panda is listed by the World Conservation Union as a Threatened Species. Two bacterial isolates with potential cellulolytic activity were isolated from Giant Panda fecal samples and cultured on selective media CMC (carboxymethyl cellulose) agar and CMC-Congo Red agar using various methods of inoculation. After incubation, clearance zones around colonies were observed and used as qualitative assays for cellulose digestion. Polymerase chain reaction amplification of the 16S rRNA gene was completed and species identification was done based on the BLAST result of 16S rRNA sequence obtained using Sanger sequencing. Once the cellulase activity is confirmed, genomic DNA of the bacteria will be extracted and used for whole genome shotgun sequencing. Illumina next generation sequencing platform will be adopted as it yields high-throughput information, providing a better understanding of cellulose digestion and the molecular genetic pathways to renewable sources of biofuels. Researchers have identified multiple cellulose-digesting microbes in the Giant Panda gut, but few have applied such bacteria in converting cellulose into glucose to create biofuel. Cellulosic ethanol, a biofuel, is produced through the fermentation of lignocellulosic biomasses. This anaerobic process is aided by cellulose-digesting enzymes. Certain microbes, such as those present in the Giant Panda gut, can produce enzymes that cleave the glycosidic bonds of cellulose (C6H10O5) into glucose molecules (C6H12O6), which can then be fermented into ethanol

Habitat and indigenous gut microbes contribute to the plasticity of gut microbiome in oriental river prawn during rapid environmental change

PubMed Central

Chen, Po-Cheng; Weng, Francis Cheng-Hsuan; Shaw, Grace Tzun-Wen

2017-01-01

Growing evidence points out that the capacity of organisms to acclimate or adapt to new habitat conditions basically depends on their phenomic plasticity attributes, of which their gut commensal microbiota might be an essential impact factor. Especially in aquatic organisms, which are in direct and continual contact with the aquatic environment, the complex and dynamic microbiota have significant effects on health and development. However, an understanding of the relative contribution of internal sorting (host genetic) and colonization (environmental) processes is still unclear. To understand how microbial communities differ in response to rapid environmental change, we surveyed and studied the environmental and gut microbiota of native and habitat-exchanged shrimp (Macrobrachium nipponense) using 16S rRNA amplicon sequencing on the Illumina MiSeq platform. Corresponding with microbial diversity of their living water areas, the divergence in gut microbes of lake-to-river shrimp (CK) increased, while that of river-to-lake shrimp (KC) decreased. Importantly, among the candidate environment specific gut microbes in habitat-exchanged shrimp, over half of reads were associated with the indigenous bacteria in native shrimp gut, yet more candidates presented in CK may reflect the complexity of new environment. Our results suggest that shrimp gut microbiota has high plasticity when its host faces environmental changes, even over short timescales. Further, the changes in external environment might influence the gut microbiome not just by providing environment-associated microbes directly, but also by interfering with the composition of indigenous gut bacteria indirectly. PMID:28715471

Gut hormones: the future of obesity treatment?

PubMed Central

McGavigan, Anne K; Murphy, Kevin G

2012-01-01

Obesity is a major worldwide health problem. The treatment options are severely limited. The development of novel anti-obesity drugs is fraught with efficacy and safety issues. Consequently, several investigational anti-obesity drugs have failed to gain marketing approval in recent years. Anorectic gut hormones offer a potentially safe and viable option for the treatment of obesity. The prospective utility of gut hormones has improved drastically in recent years with the development of longer acting analogues. Additionally, specific combinations of gut hormones have been demonstrated to have additive anorectic effects. This article reviews the current stage of anti-obesity drugs in development, focusing on gut hormone-based therapies. PMID:22452339

Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.

PubMed

Lach, Gilliard; Schellekens, Harriet; Dinan, Timothy G; Cryan, John F

2018-01-01

The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.

The Role of Microbiota on the Gut Immunology.

PubMed

Min, Yang Won; Rhee, Poong-Lyul

2015-05-01

The human gut contains >100 trillion microbes. This microbiota plays a crucial role in the gut homeostasis. Importantly, the microbiota contributes to the development and regulation of the gut immune system. Dysbiosis of the gut microbiota could also cause several intestinal and extraintestinal diseases. Many experimental studies help us to understand the complex interplay between the host and microbiota. This review presents our current understanding of the mucosal immune system and the role of gut microbiota for the development and functionality of the mucosal immunity, with a particular focus on gut-associated lymphoid tissues, mucosal barrier, TH17 cells, regulatory T cells, innate lymphoid cells, dendritic cells, and IgA-producing B cells and plasma cells. Comparative studies using germ-free and conventionally-raised animals reveal that the presence of microbiota is important for the development and regulation of innate and adaptive immune systems. The host-microbial symbiosis seems necessary for gut homeostasis. However, the precise mechanisms by which microbiota contributes to development and functionality of the immune system remain to be elucidated. Understanding the complex interplay between the host and microbiota and further investigation of the host-microbiota relationship could provide us the insight into the therapeutic and/or preventive strategy for the disorders related to dysbiosis of the gut microbiota. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Global fits of GUT-scale SUSY models with GAMBIT

NASA Astrophysics Data System (ADS)

Athron, Peter; Balázs, Csaba; Bringmann, Torsten; Buckley, Andy; Chrząszcz, Marcin; Conrad, Jan; Cornell, Jonathan M.; Dal, Lars A.; Edsjö, Joakim; Farmer, Ben; Jackson, Paul; Krislock, Abram; Kvellestad, Anders; Mahmoudi, Farvah; Martinez, Gregory D.; Putze, Antje; Raklev, Are; Rogan, Christopher; de Austri, Roberto Ruiz; Saavedra, Aldo; Savage, Christopher; Scott, Pat; Serra, Nicola; Weniger, Christoph; White, Martin

2017-12-01

We present the most comprehensive global fits to date of three supersymmetric models motivated by grand unification: the constrained minimal supersymmetric standard model (CMSSM), and its Non-Universal Higgs Mass generalisations NUHM1 and NUHM2. We include likelihoods from a number of direct and indirect dark matter searches, a large collection of electroweak precision and flavour observables, direct searches for supersymmetry at LEP and Runs I and II of the LHC, and constraints from Higgs observables. Our analysis improves on existing results not only in terms of the number of included observables, but also in the level of detail with which we treat them, our sampling techniques for scanning the parameter space, and our treatment of nuisance parameters. We show that stau co-annihilation is now ruled out in the CMSSM at more than 95% confidence. Stop co-annihilation turns out to be one of the most promising mechanisms for achieving an appropriate relic density of dark matter in all three models, whilst avoiding all other constraints. We find high-likelihood regions of parameter space featuring light stops and charginos, making them potentially detectable in the near future at the LHC. We also show that tonne-scale direct detection will play a largely complementary role, probing large parts of the remaining viable parameter space, including essentially all models with multi-TeV neutralinos.

Metagenomics analysis of gut microbiota and immune modulation in zebrafish (Danio rerio) fed chitosan silver nanocomposites.

PubMed

Udayangani, R M C; Dananjaya, S H S; Nikapitiya, Chamilani; Heo, Gang-Joon; Lee, Jehee; De Zoysa, Mahanama

2017-07-01

In this study, we evaluated the effects of chitosan silver nanocomposites (CAgNCs) supplemented diet on gut microbial community, goblet cell density, gut morphometry and mRNA expression of immune related and mucin encoding genes in zebrafish. Zebrafish gut microbiota analysis results clearly showed the reduction of phylum Proteobacteria. However, they remained as the major bacterial group in gut with CAgNCs supplemented diet, while the abundance of phylum Fusobacteria and phylum Bacteroidetes were increased notably compared to the control diet fed fish. Total goblet cell density was significantly increased at 30 and 60 days in CAgNCs supplemented group (1.6-fold and 2.0-fold, respectively) compared to the control group indicating enhanced immune function in the gut. CAgNCs supplementation has also increased villi height significantly in the zebrafish mid gut at the end of 30 (95.5 ± 3.7 μm) and 60 days (144.40 ± 4.8 μm) compared to control diet fed fish at 30 (86.90 ± 3.7 μm) and 60 days (96.2 ± 4.8 μm). Furthermore, mRNA expression of immune related genes such as TNF-α (6.2-fold), IL-10 (5.0-fold), IL-12 (9.2-fold), IRF-1 (5.2-fold), Defbl1 (3-fold), Lyz (5.1-fold) and mucin encoding genes were significantly upregulated (above 2-fold) compared to that of control group. The current study revealed that CAgNCs supplemented diet engenders promising effects on fish gut immunity by enhancing beneficial microbial populations, goblet cell density, villi length, and transcriptional regulation of immune related and mucin encoding genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes.

PubMed

Saad, Rama; Rizkallah, Mariam R; Aziz, Ramy K

2012-11-30

The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

PubMed Central

Temko, Jamie E.; Bouhlal, Sofia; Farokhnia, Mehdi; Lee, Mary R.; Cryan, John F.; Leggio, Lorenzo

2017-01-01

Abstract Aims Accumulating evidence for the influence of the gut microbiota on the bidirectional communication along the gut-brain axis suggests a role of the gut microbiota in eating disorders (EDs) and alcohol and substance use disorders. The potential influence of altered gut microbiota (dysbiosis) on behaviors associated with such disorders may have implications for developing therapeutic interventions. Methods A systematic review of preclinical and clinical studies evaluating the gut microbiota, EDs and alcohol and substance use disorders was conducted using MEDLINE, Embase and Web of Science databases with the objective being to examine the role of the gut microbiota in behavioral correlates of these disorders. Original papers focused on the gut microbiota and potential behavioral implications were deemed eligible for consideration. Results The resulting 12 publications were limited to gut microbiota studies related to EDs and alcohol and substance use disorders. Some studies suggest that dysbiosis and gut microbial byproducts may influence the pathophysiology of EDs via direct and indirect interference with peptide hormone signaling. Additionally, dysbiosis was shown to be correlated with alcohol use disorder-related symptoms, i.e. craving, depression and anxiety. Finally, a mouse study suggests that manipulations in the gut microbiota may affect cocaine-related behaviors. Conclusions Promising, albeit preliminary, findings suggest a potential role of the gut microbiota in behavioral correlates of EDs and alcohol and substance use disorders. Short summary Preliminary evidence exists supporting the role of the gut microbiota in eating disorders and alcohol and substance use disorders, although additional investigation is needed to determine what is causative versus epiphenomenological. PMID:28482009

The giant panda gut microbiome.

PubMed

Wei, Fuwen; Wang, Xiao; Wu, Qi

2015-08-01

Giant pandas (Ailuropoda melanoleuca) are bamboo specialists that evolved from carnivores. Their gut microbiota probably aids in the digestion of cellulose and this is considered an example of gut microbiota adaptation to a bamboo diet. However, this issue remains unresolved and further functional and compositional studies are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early gut mycobiota and mother-offspring transfer.

PubMed

Schei, Kasper; Avershina, Ekaterina; Øien, Torbjørn; Rudi, Knut; Follestad, Turid; Salamati, Saideh; Ødegård, Rønnaug Astri

2017-08-24

The fungi in the gastrointestinal tract, the gut mycobiota, are now recognised as a significant part of the gut microbiota, and they may be important to human health. In contrast to the adult gut mycobiota, the establishment of the early gut mycobiota has never been described, and there is little knowledge about the fungal transfer from mother to offspring. In a prospective cohort, we followed 298 pairs of healthy mothers and offspring from 36 weeks of gestation until 2 years of age (1516 samples) and explored the gut mycobiota in maternal and offspring samples. Half of the pregnant mothers were randomised into drinking probiotic milk during and after pregnancy. The probiotic bacteria included Lactobacillus rhamnosus GG (LGG), Bifidobacterium animalis subsp. lactis Bb-12 and Lactobacillus acidophilus La-5. We quantified the fungal abundance of all the samples using qPCR of the fungal internal transcribed spacer (ITS)1 segment, and we sequenced the 18S rRNA gene ITS1 region of 90 high-quantity samples using the MiSeq platform (Illumina). The gut mycobiota was detected in most of the mothers and the majority of the offspring. The offspring showed increased odds of having detectable faecal fungal DNA if the mother had detectable fungal DNA as well (OR = 1.54, p = 0.04). The fungal alpha diversity in the offspring gut increased from its lowest at 10 days after birth, which was the earliest sampling point. The fungal diversity and fungal species showed a succession towards the maternal mycobiota as the child aged, with Debaryomyces hansenii being the most abundant species during breast-feeding and Saccharomyces cerevisiae as the most abundant after weaning. Probiotic consumption increased the gut mycobiota abundance in pregnant mothers (p = 0.01). This study provides the first insight into the early fungal establishment and the succession of fungal species in the gut mycobiota. The results support the idea that the fungal host phenotype is transferred from