Abelian gauge symmetries in F-theory and dual theories

NASA Astrophysics Data System (ADS)

Song, Peng

In this dissertation, we focus on important physical and mathematical aspects, especially abelian gauge symmetries, of F-theory compactifications and its dual formulations within type IIB and heterotic string theory. F-theory is a non-perturbative formulation of type IIB string theory which enjoys important dualities with other string theories such as M-theory and E8 x E8 heterotic string theory. One of the main strengths of F-theory is its geometrization of many physical problems in the dual string theories. In particular, its study requires a lot of mathematical tools such as advanced techniques in algebraic geometry. Thus, it has also received a lot of interests among mathematicians, and is a vivid area of research within both the physics and the mathematics community. Although F-theory has been a long-standing theory, abelian gauge symmetry in Ftheory has been rarely studied, until recently. Within the mathematics community, in 2009, Grassi and Perduca first discovered the possibility of constructing elliptically fibered varieties with non-trivial toric Mordell-Weil group. In the physics community, in 2012, Morrison and Park first made a major advancement by constructing general F-theory compactifications with U(1) abelian gauge symmetry. They found that in such cases, the elliptically-fibered Calabi-Yau manifold that F-theory needs to be compactified on has its fiber being a generic elliptic curve in the blow-up of the weighted projective space P(1;1;2) at one point. Subsequent developments have been made by Cvetic, Klevers and Piragua extended the works of Morrison and Park and constructed general F-theory compactifications with U(1) x U(1) abelian gauge symmetry. They found that in the U(1) x U(1) abelian gauge symmetry case, the elliptically-fibered Calabi-Yau manifold that F-theory needs to be compactified on has its fiber being a generic elliptic curve in the del Pezzo surface dP2. In chapter 2 of this dissertation, I bring this a step further by

Advances and perspectives in in vitro human gut fermentation modeling.

PubMed

Payne, Amanda N; Zihler, Annina; Chassard, Christophe; Lacroix, Christophe

2012-01-01

The gut microbiota is a highly specialized organ containing host-specific assemblages of microbes whereby metabolic activity directly impacts human health and disease. In vitro gut fermentation models present an unmatched opportunity of performing studies frequently challenged in humans and animals owing to ethical concerns. Multidisciplinary systems biology analyses supported by '-omics' platforms remain widely neglected in the field of in vitro gut fermentation modeling but are key to advancing the significance of these models. Model-driven experimentation using a combination of in vitro gut fermentation and in vitro human cell models represent an advanced approach in identifying complex host-microbe interactions and niches central to gut fermentation processes. The aim of this review is to highlight the advances and challenges exhibited by in vitro human gut fermentation modeling. Copyright © 2011 Elsevier Ltd. 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.

Discrete symmetries in Heterotic/F-theory duality and mirror symmetry

DOE PAGES

Cvetič, Mirjam; Grassi, Antonella; Poretschkin, Maximilian

2017-06-30

We study aspects of Heterotic/F-theory duality for compacti cations with Abelian discrete gauge symmetries. We consider F-theory compacti cations on genus-one bered Calabi-Yau manifolds with n-sections, associated with the Tate-Shafarevich group Z n. Such models are obtained by studying rst a speci c toric set-up whose associated Heterotic vector bundle has structure group Z n. By employing a conjectured Heterotic/Ftheory mirror symmetry we construct dual geometries of these original toric models, where in the stable degeneration limit we obtain a discrete gauge symmetry of order two and three, for compacti cations to six dimensions. We provide explicit constructions of mirrorpairsmore » for symmetric examples with Z 2 and Z 3, in six dimensions. The Heterotic models with symmetric discrete symmetries are related in eld theory to a Higgsing of Heterotic models with two symmetric abelian U(1) gauge factors, where due to the Stuckelberg mechanism only a diagonal U(1) factor remains massless, and thus after Higgsing only a diagonal discrete symmetry of order n is present in the Heterotic models and detected via Heterotic/F-theory duality. These constructions also provide further evidence for the conjectured mirror symmetry in Heterotic/F-theory at the level of brations with torsional sections and those with multi-sections.« less

Discrete symmetries in Heterotic/F-theory duality and mirror symmetry

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

Cvetič, Mirjam; Grassi, Antonella; Poretschkin, Maximilian

We study aspects of Heterotic/F-theory duality for compacti cations with Abelian discrete gauge symmetries. We consider F-theory compacti cations on genus-one bered Calabi-Yau manifolds with n-sections, associated with the Tate-Shafarevich group Z n. Such models are obtained by studying rst a speci c toric set-up whose associated Heterotic vector bundle has structure group Z n. By employing a conjectured Heterotic/Ftheory mirror symmetry we construct dual geometries of these original toric models, where in the stable degeneration limit we obtain a discrete gauge symmetry of order two and three, for compacti cations to six dimensions. We provide explicit constructions of mirrorpairsmore » for symmetric examples with Z 2 and Z 3, in six dimensions. The Heterotic models with symmetric discrete symmetries are related in eld theory to a Higgsing of Heterotic models with two symmetric abelian U(1) gauge factors, where due to the Stuckelberg mechanism only a diagonal U(1) factor remains massless, and thus after Higgsing only a diagonal discrete symmetry of order n is present in the Heterotic models and detected via Heterotic/F-theory duality. These constructions also provide further evidence for the conjectured mirror symmetry in Heterotic/F-theory at the level of brations with torsional sections and those with multi-sections.« less

[The role of gut instinct is an important subject].

PubMed

Snoek, Jos W

2010-01-01

The role of gut instinct in general practice is an important topic. The reliance on gut instinct by experienced doctors is thought to be a form of intuitive decision-making which fits in with System 1 processes in the dual process model in higher cognition. Special mention is made of the theories on intuitive decision-making by the famous Dutch psychologist De Groot, who, when investigating thought processes of chess masters more than half a century ago, developed a fundamental theory on intuitive heuristics. Further studies on the determinants and conditions under which heuristics, such as the reliance on gut instinct, are applied in clinical practice are very welcome.

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

Maximal sfermion flavour violation in super-GUTs

DOE PAGES

Ellis, John; Olive, Keith A.; Velasco-Sevilla, Liliana

2016-10-20

We consider supersymmetric grand unified theories with soft supersymmetry-breaking scalar masses m 0 specified above the GUT scale (super-GUTs) and patterns of Yukawa couplings motivated by upper limits on flavour-changing interactions beyond the Standard Model. If the scalar masses are smaller than the gaugino masses m 1/2, as is expected in no-scale models, the dominant effects of renormalisation between the input scale and the GUT scale are generally expected to be those due to the gauge couplings, which are proportional to m 1/2 and generation independent. In this case, the input scalar masses m 0 may violate flavour maximally, amore » scenario we call MaxSFV, and there is no supersymmetric flavour problem. As a result, we illustrate this possibility within various specific super-GUT scenarios that are deformations of no-scale gravity« less

Laminar fMRI and computational theories of brain function.

PubMed

Stephan, K E; Petzschner, F H; Kasper, L; Bayer, J; Wellstein, K V; Stefanics, G; Pruessmann, K P; Heinzle, J

2017-11-02

Recently developed methods for functional MRI at the resolution of cortical layers (laminar fMRI) offer a novel window into neurophysiological mechanisms of cortical activity. Beyond physiology, laminar fMRI also offers an unprecedented opportunity to test influential theories of brain function. Specifically, hierarchical Bayesian theories of brain function, such as predictive coding, assign specific computational roles to different cortical layers. Combined with computational models, laminar fMRI offers a unique opportunity to test these proposals noninvasively in humans. This review provides a brief overview of predictive coding and related hierarchical Bayesian theories, summarises their predictions with regard to layered cortical computations, examines how these predictions could be tested by laminar fMRI, and considers methodological challenges. We conclude by discussing the potential of laminar fMRI for clinically useful computational assays of layer-specific information processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Magnetized string cosmological models of accelerated expansion of the Universe in f(R,T) theory of gravity

NASA Astrophysics Data System (ADS)

Pradhan, Anirudh; Jaiswal, Rekha

A class of spatially homogeneous and anisotropic Bianchi-V massive string models have been studied in the modified f(R,T)-theory of gravity proposed by Harko et al. [Phys. Rev. D 84:024020, 2011] in the presence of magnetic field. For a specific choice of f(R,T)=f1(R) + f2(T), where f1(R) = ν1R and f2(T) = ν2T; ν1, ν2 being arbitrary parameters, solutions of modified gravity field equations have been generated. To find the deterministic solution of the field equations, we have considered the time varying deceleration parameter which is consistent with observational data of standard cosmology (SNIa, BAO and CMB). As a result to study the transit behavior of Universe, we consider a law of variation for the specifically chosen scale factor, which yields a time-dependent deceleration parameter comprising a class of models that depicts a transition of the Universe from the early decelerated phase to the recent accelerating phase. In this context, for the model of the Universe, the field equations are solved and corresponding cosmological aspects have been discussed. The Energy conditions in this modified gravity theory are also studied. Stability analysis of the solutions through cosmological perturbation is performed and it is concluded that the expanding solution is stable against the perturbation with respect to anisotropic spatial direction. Some physical and geometric properties of the models are also discussed.

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

Bianchi-III cosmological model with BVDP in modified f(R,T) theory

NASA Astrophysics Data System (ADS)

Mishra, R. K.; Dua, Heena; Chand, Avtar

2018-06-01

In present paper, we have investigated Bianchi type-III cosmological model in modified f(R,T) theory of gravity as proposed by Harko et al. (Phys. Rev. D 84:024020, 2011). To find the solution of field equations, we have used i) bilinear varying deceleration parameter (BVDP) (Mishra et al. in Astrophys. Space Sci. 361:259, 2016b) ii) the fact that expansion scalar of the space-time is proportional to the one of the components of the shear scalar. Physical and geometrical properties of the model have also been discussed along with the pictorial representation of various parameters. We have observed that presented model is compatible with the recent cosmological observations.

Talking theory, talking therapy: Emmy Gut and John Bowlby.

PubMed

Ross, Lynda R

2006-06-01

Emmy Gut was a psychotherapist who developed, in her later years, a unique theory distinguishing between "productive" and "unproductive" depression. Dr. John Bowlby was a leading psychoanalyst famous for his work on attachment theory. After the death of her second husband, Emmy contacted John because his work on mourning and grief spoke to her own depressed state. Although her views of the world and of her relationship with John were clearly coloured by bouts of depression, she was profoundly influenced by her personal, therapeutic, and intellectual involvement with him. Evidence of his influence is seen in the volumes of correspondence flowing between them beginning in 1971 and continuing until John's death in 1990. During that time, Emmy wrote more than 100-some very lengthy-letters to John. Much of her correspondence was devoted to discussions about their often ambiguous and conflicted therapeutic relationship. Through an analysis of attachment theory and the nature of the client-therapist alliance, this paper offers insights into the effects that imbalances in power, expectations, and shifting needs can play in the recovery process.

Isotropic cosmological models in F(T,TG) theory

NASA Astrophysics Data System (ADS)

Sharif, M.; Nazir, Kanwal

2016-09-01

This paper is devoted to study evolution of the isotropic universe models in the framework of F(T,TG) gravity (T represents torsion scalar and TG is the teleparallel equivalent of the Gauss-Bonnet (GB) term). We construct F(T,TG) models by taking different eras of the universe like non-relativistic and relativistic matter eras, dark energy (DE) dominated era and their combinations. It is found that the reconstructed models indicate decreasing behavior for DE dominated era and its combination with other eras. We also discuss stability of each reconstructed model. Finally, we evaluate equation of state (EoS) parameter by considering two models and study its behavior graphically.

F-theory on all toric hypersurface fibrations and its Higgs branches

DOE PAGES

Klevers, Denis; Mayorga Pena, Damian Kaloni; Oehlmann, Paul-Konstantin; ...

2015-01-27

We consider F-theory compactifications on genus-one fibered Calabi-Yau manifolds with their fibers realized as hypersurfaces in the toric varieties associated to the 16 reflexive 2D polyhedra. We present a base-independent analysis of the codimension one, two and three singularities of these fibrations. We use these geometric results to determine the gauge groups, matter representations, 6D matter multiplicities and 4D Yukawa couplings of the corresponding effective theories. All these theories have a non-trivial gauge group and matter content. We explore the network of Higgsings relating these theories. Such Higgsings geometrically correspond to extremal transitions induced by blow-ups in the 2D toric varieties. We recover the 6D effective theories of all 16 toric hypersurface fibrations by repeatedly Higgsing the theories that exhibit Mordell-Weil torsion. We find that the three Calabi-Yau manifolds without section, whose fibers are given by the toric hypersurfaces inmore » $$\\mathbb P^{2}$$, $$\\mathbb P^{1}$$ × $$\\mathbb P^{1}$$ and the recently studied $$\\mathbb P^{2}$$ (1,1, 2) , yield F-theory realizations of SUGRA theories with discrete gauge groups $$\\mathbb Z$$ 3, $$\\mathbb Z$$ 2 and $$\\mathbb Z$$ 4.This opens up a whole new arena for model building with discrete global symmetries in F-theory. In these three manifolds, we also find codimension two I 2-fibers supporting matter charged only under these discrete gauge groups. Their 6D matter multiplicities are computed employing ideal techniques and the associated Jacobian fibrations. Here, we also show that the Jacobian of the biquadric fibration has one rational section, yielding one U(1)-gauge field in F-theory. Furthermore, the elliptically fibered Calabi-Yau manifold based on dP 1 has a U(1)-gauge field induced by a non-toric rational section. In this model, we find the first F-theory realization of matter with U(1)-charge q = 3.« less

Neutrino assisted GUT baryogenesis revisited

NASA Astrophysics Data System (ADS)

Huang, Wei-Chih; Päs, Heinrich; Zeißner, Sinan

2018-03-01

Many grand unified theory (GUT) models conserve the difference between the baryon and lepton number, B -L . These models can create baryon and lepton asymmetries from heavy Higgs or gauge boson decays with B +L ≠0 but with B -L =0 . Since the sphaleron processes violate B +L , such GUT-generated asymmetries will finally be washed out completely, making GUT baryogenesis scenarios incapable of reproducing the observed baryon asymmetry of the Universe. In this work, we revisit the idea to revive GUT baryogenesis, proposed by Fukugita and Yanagida, where right-handed neutrinos erase the lepton asymmetry before the sphaleron processes can significantly wash out the original B +L asymmetry, and in this way one can prevent a total washout of the initial baryon asymmetry. By solving the Boltzmann equations numerically for baryon and lepton asymmetries in a simplified 1 +1 flavor scenario, we can confirm the results of the original work. We further generalize the analysis to a more realistic scenario of three active and two right-handed neutrinos to highlight flavor effects of the right-handed neutrinos. Large regions in the parameter space of the Yukawa coupling and the right-handed neutrino mass featuring successful baryogenesis are identified.

The toric SO(10) F-theory landscape

NASA Astrophysics Data System (ADS)

Buchmüller, W.; Dierigl, M.; Oehlmann, P.-K.; Rühle, F.

2017-12-01

Supergravity theories in more than four dimensions with grand unified gauge symmetries are an important intermediate step towards the ultraviolet completion of the Standard Model in string theory. Using toric geometry, we classify and analyze six-dimensional F-theory vacua with gauge group SO(10) taking into account Mordell-Weil U(1) and discrete gauge factors. We determine the full matter spectrum of these models, including charged and neutral SO(10) singlets. Based solely on the geometry, we compute all matter multiplicities and confirm the cancellation of gauge and gravitational anomalies independent of the base space. Particular emphasis is put on symmetry enhancements at the loci of matter fields and to the frequent appearance of superconformal points. They are linked to non-toric Kähler deformations which contribute to the counting of degrees of freedom. We compute the anomaly coefficients for these theories as well by using a base-independent blow-up procedure and superconformal matter transitions. Finally, we identify six-dimensional supergravity models which can yield the Standard Model with high-scale supersymmetry by further compactification to four dimensions in an Abelian flux background.

Dark Matter from SUGRA GUTs: mSUGRA, NUSUGRA and Yukawa-unified SUGRA

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

Baer, Howard

2009-09-08

Gravity-mediated SUSY breaking models with R-parity conservation give rise to dark matter in the universe. I review neutralino dark matter in the minimal supergravity model (mSUGRA), models with non-universal soft SUSY breaking terms (NUSUGRA) which yield a well-tempered neutralino, and models with unified Yukawa couplings at the GUT scale (as may occur in an SO(10) SUSY GUT theory). These latter models have difficulty accomodating neutralino dark matter, but work very well if the dark matter particles are axions and axinos.

Reconstructing a f ( R ) theory from the α-Attractors

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

Miranda, T.; Fabris, J. C.; Piattella, O. F., E-mail: tays.andrade@aluno.ufes.br, E-mail: oliver.piattella@pq.cnpq.br, E-mail: fabris@pq.cnpq.br

We show an analogy at high curvature between a f ( R ) = R + aR {sup n} {sup −} {sup 1} + bR {sup 2} theory and the α-Attractors. We calculate the expressions of the parameters a , b and n as functions of α and the predictions of the model f ( R ) = R + aR {sup n} {sup −} {sup 1} + bR {sup 2} on the scalar spectral index n {sub s} and the tensor-to-scalar ratio r . We find that the power law correction R {sup n} {sup −} {sup 1} allowsmore » for a production of gravitational waves enhanced with respect to the one in the Starobinsky model, while maintaining a viable prediction on n {sub s}. We numerically reconstruct the full α-Attractors class of models testing the goodness of our high-energy approximation f ( R ) = R + aR {sup n} {sup −} {sup 1} + bR {sup 2}. Moreover, we also investigate the case of a single power law f ( R ) = γ R {sup 2} {sup −} {sup δ} theory, with γ and δ free parameters. We calculate analytically the predictions of this model on the scalar spectral index n {sub s} and the tensor-to-scalar ratio r and the values of δ which are allowed from the current observational results. We find that −0.015 < δ < 0.016, confirming once again the excellent agreement between the Starobinsky model and observation.« less

Neutron Star Models in Alternative Theories of Gravity

NASA Astrophysics Data System (ADS)

Manolidis, Dimitrios

We study the structure of neutron stars in a broad class of alternative theories of gravity. In particular, we focus on Scalar-Tensor theories and f(R) theories of gravity. We construct static and slowly rotating numerical star models for a set of equations of state, including a polytropic model and more realistic equations of state motivated by nuclear physics. Observable quantities such as masses, radii, etc are calculated for a set of parameters of the theories. Specifically for Scalar-Tensor theories, we also calculate the sensitivities of the mass and moment of inertia of the models to variations in the asymptotic value of the scalar field at infinity. These quantities enter post-Newtonian equations of motion and gravitational waveforms of two body systems that are used for gravitational-wave parameter estimation, in order to test these theories against observations. The construction of numerical models of neutron stars in f(R) theories of gravity has been difficult in the past. Using a new formalism by Jaime, Patino and Salgado we were able to construct models with high interior pressure, namely pc > rho c/3, both for constant density models and models with a polytropic equation of state. Thus, we have shown that earlier objections to f(R) theories on the basis of the inability to construct viable neutron star models are unfounded.

Light bending in F [ g (□) R ] extended gravity theories

NASA Astrophysics Data System (ADS)

Giacchini, Breno L.; Shapiro, Ilya L.

2018-05-01

We show that in the weak field limit the light deflection alone cannot distinguish between different R + F [ g (□) R ] models of gravity, where F and g are arbitrary functions. This does not imply, however, that in all these theories an observer will see the same deflection angle. Owed to the need to calibrate the Newton constant, the deflection angle may be model-dependent after all necessary types of measurements are taken into account.

Possible antigravity regions in F(R) theory?

NASA Astrophysics Data System (ADS)

Bamba, Kazuharu; Nojiri, Shin'ichi; Odintsov, Sergei D.; Sáez-Gómez, Diego

2014-03-01

We construct an F(R) gravity theory corresponding to the Weyl invariant two scalar field theory. We investigate whether such F(R) gravity can have the antigravity regions where the Weyl curvature invariant does not diverge at the Big Bang and Big Crunch singularities. It is revealed that the divergence cannot be evaded completely but can be much milder than that in the original Weyl invariant two scalar field theory.

Gauge backgrounds and zero-mode counting in F-theory

NASA Astrophysics Data System (ADS)

Bies, Martin; Mayrhofer, Christoph; Weigand, Timo

2017-11-01

Computing the exact spectrum of charged massless matter is a crucial step towards understanding the effective field theory describing F-theory vacua in four dimensions. In this work we further develop a coherent framework to determine the charged massless matter in F-theory compactified on elliptic fourfolds, and demonstrate its application in a concrete example. The gauge background is represented, via duality with M-theory, by algebraic cycles modulo rational equivalence. Intersection theory within the Chow ring allows us to extract coherent sheaves on the base of the elliptic fibration whose cohomology groups encode the charged zero-mode spectrum. The dimensions of these cohomology groups are computed with the help of modern techniques from algebraic geometry, which we implement in the software gap. We exemplify this approach in models with an Abelian and non-Abelian gauge group and observe jumps in the exact massless spectrum as the complex structure moduli are varied. An extended mathematical appendix gives a self-contained introduction to the algebro-geometric concepts underlying our framework.

Origin of Abelian gauge symmetries in heterotic/F-theory duality

DOE PAGES

Cvetič, Mirjam; Grassi, Antonella; Klevers, Denis; ...

2016-04-07

Here, we study aspects of heterotic/F-theory duality for compactifications with Abelian gauge symmetries. We consider F-theory on general Calabi-Yau manifolds with a rank one Mordell-Weil group of rational sections. By rigorously performing the stable degeneration limit in a class of toric models, and also derive both the Calabi-Yau geometry and the spectral cover describing the vector bundle in the heterotic dual theory. We carefully investigate the spectral cover employing the group law on the elliptic curve in the heterotic theory. We find in explicit examples that there are three different classes of heterotic duals that have U(1) factors in theirmore » low energy effective theories: split spectral covers describing bundles with S(U(m) x U(1)) structure group, spectral covers containing torsional sections that seem to give rise to bundles with SU(m) x Z_k structure group and bundles with purely non-Abelian structure groups having a centralizer in E_8 containing a U(1) factor. In the former two cases, it is required that the elliptic fibration on the heterotic side has a non-trivial Mordell-Weil group. And while the number of geometrically massless U(1)'s is determined entirely by geometry on the F-theory side, on the heterotic side the correct number of U(1)'s is found by taking into account a Stuckelberg mechanism in the lower-dimensional effective theory. Finally, in geometry, this corresponds to the condition that sections in the two half K3 surfaces that arise in the stable degeneration limit of F-theory can be glued together globally.« less

The role of gut microbiota in health and disease: In vitro modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut.

PubMed

von Martels, Julius Z H; Sadaghian Sadabad, Mehdi; Bourgonje, Arno R; Blokzijl, Tjasso; Dijkstra, Gerard; Faber, Klaas Nico; Harmsen, Hermie J M

2017-04-01

The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition. Functional studies using (in vitro) gut models are required to investigate the precise interactions that occur between specific bacteria (or bacterial mixtures) and gut epithelial cells. As most gut bacteria are obligate or facultative anaerobes, studying their effect on oxygen-requiring human gut epithelial cells is technically challenging. Still, several (anaerobic) bacterial-epithelial co-culture systems have recently been developed that mimic host-microbe interactions occurring in the human gut, including 1) the Transwell "apical anaerobic model of the intestinal epithelial barrier", 2) the Host-Microbiota Interaction (HMI) module, 3) the "Human oxygen-Bacteria anaerobic" (HoxBan) system, 4) the human gut-on-a-chip and 5) the HuMiX model. This review discusses the role of gut microbiota in health and disease and gives an overview of the characteristics and applications of these novel host-microbe co-culture systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Bacterium Frischella perrara Causes Scab Formation in the Gut of its Honeybee Host

PubMed Central

Bartlett, Kelsey D.; Moran, Nancy A.

2015-01-01

ABSTRACT Honeybees harbor well-defined bacterial communities in their guts. The major members of these communities appear to benefit the host, but little is known about how they interact with the host and specifically how they interface with the host immune system. In the pylorus, a short region between the midgut and hindgut, honeybees frequently exhibit scab-like structures on the epithelial gut surface. These structures are reminiscent of a melanization response of the insect immune system. Despite the wide distribution of this phenotype in honeybee populations, its cause has remained elusive. Here, we show that the presence of a common member of the bee gut microbiota, the gammaproteobacterium Frischella perrara, correlates with the appearance of the scab phenotype. Bacterial colonization precedes scab formation, and F. perrara specifically localizes to the melanized regions of the host epithelium. Under controlled laboratory conditions, we demonstrate that exposure of microbiota-free bees to F. perrara but not to other bacteria results in scab formation. This shows that F. perrara can become established in a spatially restricted niche in the gut and triggers a morphological change of the epithelial surface, potentially due to a host immune response. As an intermittent colonizer, this bacterium holds promise for addressing questions of community invasion in a simple yet relevant model system. Moreover, our results show that gut symbionts of bees engage in differential host interactions that are likely to affect gut homeostasis. Future studies should focus on how these different gut bacteria impact honeybee health. PMID:25991680

The chemo-mechanical coupled model for F(1)F(0)-motor.

PubMed

Xu, Lizhong; Liu, Fang

2012-04-01

F(1)F(0)-motor (ATP synthase) is the universal enzyme in biological energy conversion that is present in the membranes of mitochondria, chloroplasts and bacteria. It uses the energy of the proton gradient across the membrane to synthesize ATP. Previous theory and model about rotation of the ATP synthase is reviewed, then a novel chemo-mechanical coupled model for rotation of the F(1)F(0)-motor is proposed. In the model, more events are considered simultaneously that includes the movement of F(1), the movement of F(0), reactions at F(1) and reactions at F(0). Using the model, the possible substep modes of the rotation for F(1)F(0) are predicted, the dependence of the motor efficiency and its rotation rate on the rigidity of the γ shaft is investigated. We conclude that the γ shaft has a large rotation rate for a limited driving potential because two ends of the γ shaft can rotate alternately for its flexibility. The flexibility also makes the efficiency of F(1)F(0) drop because elastic twisting deformation power is needed during alternate rotation of the γ shaft at two ends. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polymers in the gut compress the colonic mucus hydrogel.

PubMed

Datta, Sujit S; Preska Steinberg, Asher; Ismagilov, Rustem F

2016-06-28

Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host-microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer-mucus interactions can be described using a thermodynamic model based on Flory-Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice-whose microbiota degrade gut polymers-did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes.

From Network Analysis to Functional Metabolic Modeling of the Human Gut Microbiota.

PubMed

Bauer, Eugen; Thiele, Ines

2018-01-01

An important hallmark of the human gut microbiota is its species diversity and complexity. Various diseases have been associated with a decreased diversity leading to reduced metabolic functionalities. Common approaches to investigate the human microbiota include high-throughput sequencing with subsequent correlative analyses. However, to understand the ecology of the human gut microbiota and consequently design novel treatments for diseases, it is important to represent the different interactions between microbes with their associated metabolites. Computational systems biology approaches can give further mechanistic insights by constructing data- or knowledge-driven networks that represent microbe interactions. In this minireview, we will discuss current approaches in systems biology to analyze the human gut microbiota, with a particular focus on constraint-based modeling. We will discuss various community modeling techniques with their advantages and differences, as well as their application to predict the metabolic mechanisms of intestinal microbial communities. Finally, we will discuss future perspectives and current challenges of simulating realistic and comprehensive models of the human gut microbiota.

A viable logarithmic f(R) model for inflation

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

Amin, M.; Khalil, S.; Salah, M.

2016-08-18

Inflation in the framework of f(R) modified gravity is revisited. We study the conditions that f(R) should satisfy in order to lead to a viable inflationary model in the original form and in the Einstein frame. Based on these criteria we propose a new logarithmic model as a potential candidate for f(R) theories aiming to describe inflation consistent with observations from Planck satellite (2015). The model predicts scalar spectral index 0.9615

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.

Vectorlike particles, Z‧ and Yukawa unification in F-theory inspired E6

NASA Astrophysics Data System (ADS)

Karozas, Athanasios; Leontaris, George K.; Shafi, Qaisar

2018-03-01

We explore the low energy implications of an F-theory inspired E6 model whose breaking yields, in addition to the MSSM gauge symmetry, a Z‧ gauge boson associated with a U (1) symmetry broken at the TeV scale. The zero mode spectrum of the effective low energy theory is derived from the decomposition of the 27 and 27 ‾ representations of E6 and we parametrise their multiplicities in terms of a minimum number of flux parameters. We perform a two-loop renormalisation group analysis of the gauge and Yukawa couplings of the effective theory model and estimate lower bounds on the new vectorlike particles predicted in the model. We compute the third generation Yukawa couplings in an F-theory context assuming an E8 point of enhancement and express our results in terms of the local flux densities associated with the gauge symmetry breaking. We find that their values are compatible with the ones computed by the renormalisation group equations, and we identify points in the parameter space of the flux densities where the t - b - τ Yukawa couplings unify.

Impact of the gut microbiota on rodent models of human disease.

PubMed

Hansen, Axel Kornerup; Hansen, Camilla Hartmann Friis; Krych, Lukasz; Nielsen, Dennis Sandris

2014-12-21

Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 10(14) organisms dispersed on approximately 1000 different species. Today, diagnostics, in contrast to previous cultivation techniques, allow the identification of close to 100% of bacterial species. This has revealed that a range of animal models within different research areas, such as diabetes, obesity, cancer, allergy, behavior and colitis, are affected by their gut microbiota. Correlation studies may for some diseases show correlation between gut microbiota composition and disease parameters higher than 70%. Some disease phenotypes may be transferred when recolonizing germ free mice. The mechanistic aspects are not clear, but some examples on how gut bacteria stimulate receptors, metabolism, and immune responses are discussed. A more deeper understanding of the impact of microbiota has its origin in the overall composition of the microbiota and in some newly recognized species, such as Akkermansia muciniphila, Segmented filamentous bacteria and Faecalibacterium prausnitzii, which seem to have an impact on more or less severe disease in specific models. Thus, the impact of the microbiota on animal models is of a magnitude that cannot be ignored in future research. Therefore, either models with specific microbiota must be developed, or the microbiota must be characterized in individual studies and incorporated into data evaluation.

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.

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

Modified first-order Hořava-Lifshitz gravity: Hamiltonian analysis of the general theory and accelerating FRW cosmology in a power-law F(R) model

NASA Astrophysics Data System (ADS)

Carloni, Sante; Chaichian, Masud; Nojiri, Shin'Ichi; Odintsov, Sergei D.; Oksanen, Markku; Tureanu, Anca

2010-09-01

We propose the most general modified first-order Hořava-Lifshitz gravity, whose action does not contain time derivatives higher than the second order. The Hamiltonian structure of this theory is studied in all the details in the case of the spatially-flat Friedmann-Robertson-Walker (FRW) space-time, demonstrating many of the features of the general theory. It is shown that, with some plausible assumptions, including the projectability of the lapse function, this model is consistent. As a large class of such theories, the modified Hořava-Lifshitz F(R) gravity is introduced. The study of its ultraviolet properties shows that its z=3 version seems to be renormalizable in the same way as the original Hořava-Lifshitz proposal. The Hamiltonian analysis of the modified Hořava-Lifshitz F(R) gravity shows that it is in general a consistent theory. The F(R) gravity action is also studied in the fixed-gauge form, where the appearance of a scalar field is particularly illustrative. Then the spatially-flat FRW cosmology for this F(R) gravity is investigated. It is shown that a special choice of parameters for this theory leads to the same equations of motion as in the case of traditional F(R) gravity. Nevertheless, the cosmological structure of the modified Hořava-Lifshitz F(R) gravity turns out to be much richer than for its traditional counterpart. The emergence of multiple de Sitter solutions indicates the possibility of unification of early-time inflation with late-time acceleration within the same model. Power-law F(R) theories are also investigated in detail. It is analytically shown that they have a quite rich cosmological structure: early-/late-time cosmic acceleration of quintessence, as well as of phantom types. Also it is demonstrated that all the four known types of finite-time future singularities may occur in the power-law Hořava-Lifshitz F(R) gravity. Finally, a covariant proposal for (renormalizable) F(R) gravity within the Hořava-Lifshitz spirit is

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.

Polymers in the gut compress the colonic mucus hydrogel

PubMed Central

Datta, Sujit S.; Preska Steinberg, Asher

2016-01-01

Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host–microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer–mucus interactions can be described using a thermodynamic model based on Flory–Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice—whose microbiota degrade gut polymers—did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes. PMID:27303035

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.

Statefinder diagnostic and constraints on the Palatini f(R) gravity theories

NASA Astrophysics Data System (ADS)

Cao, Shu-Lei; Li, Song; Yu, Hao-Ran; Zhang, Tong-Jie

2018-03-01

We focus on a series of f(R) gravity theories in Palatini formalism to investigate the probabilities of producing late-time acceleration for the flat Friedmann-Robertson-Walker (FRW) universe. We apply a statefinder diagnostic to these cosmological models for chosen series of parameters to see if they can be distinguished from one another. The diagnostic involves the statefinder pair {r, s}, where r is derived from the scale factor a and its higher derivatives with respect to the cosmic time t, and s is expressed by r and the deceleration parameter q. In conclusion, we find that although two types of f(R) theories: (i) f(R) = R + αRm – βR ‑n and (ii) f(R) = R + α ln R – β can lead to late-time acceleration, their evolutionary trajectories in the r – s and r – q planes reveal different evolutionary properties, which certainly justify the merits of the statefinder diagnostic. Additionally, we utilize the observational Hubble parameter data (OHD) to constrain these models of f(R) gravity. As a result, except for m = n = 1/2 in case (i), α = 0 in case (i) and case (ii) allow the ΛCDM model to exist in the 1σ confidence region. After applying the statefinder diagnostic to the best-fit models, we find that all the best-fit models are capable of going through the deceleration/acceleration transition stage with a late-time acceleration epoch, and all these models turn to the de Sitter point ({r, s} = {1, 0}) in the future. Also, the evolutionary differences between these models are distinct, especially in the r – s plane, which makes the statefinder diagnostic more reliable in discriminating cosmological models.

Flavor structure in F-theory compactifications

NASA Astrophysics Data System (ADS)

Hayashi, Hirotaka; Kawano, Teruhiko; Tsuchiya, Yoichi; Watari, Taizan

2010-08-01

F-theory is one of frameworks in string theory where supersymmetric grand unification is accommodated, and all the Yukawa couplings and Majorana masses of righthanded neutrinos are generated. Yukawa couplings of charged fermions are generated at codimension-3 singularities, and a contribution from a given singularity point is known to be approximately rank 1. Thus, the approximate rank of Yukawa matrices in low-energy effective theory of generic F-theory compactifications are minimum of either the number of generations N gen = 3 or the number of singularity points of certain types. If there is a geometry with only one E 6 type point and one D 6 type point over the entire 7-brane for SU(5) gauge fields, F-theory compactified on such a geometry would reproduce approximately rank-1 Yukawa matrices in the real world. We found, however, that there is no such geometry. Thus, it is a problem how to generate hierarchical Yukawa eigenvalues in F-theory compactifications. A solution in the literature so far is to take an appropriate factorization limit. In this article, we propose an alternative solution to the hierarchical structure problem (which requires to tune some parameters) by studying how zero mode wavefunctions depend on complex structure moduli. In this solution, the N gen × N gen CKM matrix is predicted to have only N gen entries of order unity without an extra tuning of parameters, and the lepton flavor anarchy is predicted for the lepton mixing matrix. The hierarchy among the Yukawa eigenvalues of the down-type and charged lepton sector is predicted to be smaller than that of the up-type sector, and the Majorana masses of left-handed neutrinos generated through the see-saw mechanism have small hierarchy. All of these predictions agree with what we observe in the real world. We also obtained a precise description of zero mode wavefunctions near the E 6 type singularity points, where the up-type Yukawa couplings are generated.

Altered gut microbiome in a mouse model of Gulf War Illness causes neuroinflammation and intestinal injury via leaky gut and TLR4 activation.

PubMed

Alhasson, Firas; Das, Suvarthi; Seth, Ratanesh; Dattaroy, Diptadip; Chandrashekaran, Varun; Ryan, Caitlin N; Chan, Luisa S; Testerman, Traci; Burch, James; Hofseth, Lorne J; Horner, Ronnie; Nagarkatti, Mitzi; Nagarkatti, Prakash; Lasley, Stephen M; Chatterjee, Saurabh

2017-01-01

Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease in tight junction protein Occludin with a concomitant increase in Claudin-2, a signature of a leaky gut. Resultant leaching of gut caused portal endotoxemia that led to upregulation of toll like receptor 4 (TLR4) activation in the small intestine and the brain. TLR4 knock out mice and mice that had gut decontamination showed significant decrease in tyrosine nitration and inflammatory mediators IL1β and MCP-1 in both the small intestine and frontal cortex. These events signified that gut dysbiosis with simultaneous leaky gut and systemic endotoxemia-induced TLR4 activation contributes to GW chemical-induced neuroinflammation and gastrointestinal disturbances.

The vertical, the horizontal and the rest: anatomy of the middle cohomology of Calabi-Yau fourfolds and F-theory applications

NASA Astrophysics Data System (ADS)

Braun, A. P.; Watari, T.

2015-01-01

The four-form field strength in F-theory compactifications on Calabi-Yau four-folds takes its value in the middle cohomology group H 4. The middle cohomology is decomposed into a vertical, a horizontal and a remaining component, all three of which are present in general. We argue that a flux along the remaining or vertical component may break some symmetry, while a purely horizontal flux does not influence the unbroken part of the gauge group or the net chirality of charged matter fields. This makes the decomposition crucial to the counting of flux vacua in the context of F-theory GUTs. We use mirror symmetry to derive a combinatorial formula for the dimensions of these components applicable to any toric Calabi-Yau hypersurface, and also make a partial attempt at providing a geometric characterization of the four-cycles Poincaré dual to the remaining component of H 4. It is also found in general elliptic Calabi-Yau fourfolds supporting SU(5) gauge symmetry that a remaining component can be present, for example, in a form crucial to the symmetry breaking SU(5) - → SU(3) C × SU(2) L × U(1) Y . The dimension of the horizontal component is used to derive an estimate of the statistical distribution of the number of generations and the rank of 7-brane gauge groups in the landscape of F-theory flux vacua.

Modeling the viscoplastic behavior of Inconel 718 at 1200 F

NASA Technical Reports Server (NTRS)

Abdel-Kader, M. S.; Eftis, J.; Jones, D. L.

1988-01-01

A large number of tests, including tensile, creep, fatigue, and creep-fatigue were performed to characterize the mechanical properties of Inconel 718 (a nickel based superalloy) at 1200 F, the operating temperature for turbine blades. In addition, a few attempts were made to model the behavior of Inconel 718 at 1200 F using viscoplastic theories. The Chaboche theory of viscoplasticity can model a wide variety of mechanical behavior, including monotonic, sustained, and cyclic responses of homogeneous, initially-isotropic, strain hardening (or softening) materials. It is shown how the Chaboche theory can be used to model the viscoplastic behavior of Inconel 718 at 1200 F. First, an algorithm was developed to systematically determine the material parameters of the Chaboche theory from uniaxial tensile, creep, and cyclic data. The algorithm is general and can be used in conjunction with similar high temperature materials. A sensitivity study was then performed and an optimal set of Chaboche's parameters were obtained. This study has also indicated the role of each parameter in modeling the response to different loading conditions.

Theory of resonant x-ray emission spectra in compounds with localized f electrons

NASA Astrophysics Data System (ADS)

Kolorenč, Jindřich

2018-05-01

I discuss a theoretical description of the resonant x-ray emission spectroscopy (RXES) that is based on the Anderson impurity model. The parameters entering the model are determined from material-specific LDA+DMFT calculations. The theory is applicable across the whole f series, not only in the limits of nearly empty (La, Ce) or nearly full (Yb) valence f shell. Its performance is illustrated on the pressure-enhanced intermediate valency of elemental praseodymium. The obtained results are compared to the usual interpretation of RXES, which assumes that the spectrum is a superposition of several signals, each corresponding to one configuration of the 4f shell. The present theory simplifies to such superposition only if nearly all effects of hybridization of the 4f shell with the surrounding states are neglected. Although the assumption of negligible hybridization sounds reasonable for lanthanides, the explicit calculations show that it substantially distorts the analysis of the RXES data.

No Gut No Gain! Enteral Bile Acid Treatment Preserves Gut Growth but Not Parenteral Nutrition-Associated Liver Injury in a Novel Extensive Short Bowel Animal Model.

PubMed

Villalona, Gustavo; Price, Amber; Blomenkamp, Keith; Manithody, Chandrashekhara; Saxena, Saurabh; Ratchford, Thomas; Westrich, Matthew; Kakarla, Vindhya; Pochampally, Shruthika; Phillips, William; Heafner, Nicole; Korremla, Niraja; Greenspon, Jose; Guzman, Miguel A; Kumar Jain, Ajay

2018-04-27

Parenteral nutrition (PN) provides nutrition intravenously; however, this life-saving therapy is associated with significant liver disease. Recent evidence indicates improvement in PN-associated injury in animals with intact gut treated with enteral bile acid (BA), chenodeoxycholic acid (CDCA), and a gut farnesoid X receptor (FXR) agonist, which drives the gut-liver cross talk (GLCT). We hypothesized that similar improvement could be translated in animals with short bowel syndrome (SBS). Using piglets, we developed a novel 90% gut-resected SBS model. Fifteen SBS piglets receiving PN were given CDCA or control (vehicle control) for 2 weeks. Tissue and serum were analyzed posteuthanasia. CDCA increased gut FXR (quantitative polymerase chain reaction; P = .008), but not downstream FXR targets. No difference in gut fibroblast growth factor 19 (FGF19; P = .28) or hepatic FXR (P = .75), FGF19 (P = .86), FGFR4 (P = .53), or Cholesterol 7 α-hydroxylase (P = .61) was noted. PN resulted in cholestasis; however, no improvement was noted with CDCA. Hepatic fibrosis or immunostaining for Ki67, CD3, or Cytokeratin 7 was not different with CDCA. PN resulted in gut atrophy. CDCA preserved (P = .04 vs control) gut mass and villous/crypt ratio. The median (interquartile range) for gut mass for control was 0.28 (0.17-0.34) and for CDCA was 0.33 (0.26-0.46). We note that, unlike in animals with intact gut, in an SBS animal model there is inadequate CDCA-induced activation of gut-derived signaling to cause liver improvement. Thus, it appears that activation of GLCT is critically dependent on the presence of adequate gut. This is clinically relevant because it suggests that BA therapy may not be as effective for patients with SBS. © 2018 American Society for Parenteral and Enteral Nutrition.

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

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.

Palatini formulation of f( R, T) gravity theory, and its cosmological implications

NASA Astrophysics Data System (ADS)

Wu, Jimin; Li, Guangjie; Harko, Tiberiu; Liang, Shi-Dong

2018-05-01

We consider the Palatini formulation of f( R, T) gravity theory, in which a non-minimal coupling between the Ricci scalar and the trace of the energy-momentum tensor is introduced, by considering the metric and the affine connection as independent field variables. The field equations and the equations of motion for massive test particles are derived, and we show that the independent connection can be expressed as the Levi-Civita connection of an auxiliary, energy-momentum trace dependent metric, related to the physical metric by a conformal transformation. Similar to the metric case, the field equations impose the non-conservation of the energy-momentum tensor. We obtain the explicit form of the equations of motion for massive test particles in the case of a perfect fluid, and the expression of the extra force, which is identical to the one obtained in the metric case. The thermodynamic interpretation of the theory is also briefly discussed. We investigate in detail the cosmological implications of the theory, and we obtain the generalized Friedmann equations of the f( R, T) gravity in the Palatini formulation. Cosmological models with Lagrangians of the type f=R-α ^2/R+g(T) and f=R+α ^2R^2+g(T) are investigated. These models lead to evolution equations whose solutions describe accelerating Universes at late times.

Weak coupling limit of F-theory models with MSSM spectrum and massless U(1)'s

NASA Astrophysics Data System (ADS)

Mayorga Peña, Damián Kaloni; Valandro, Roberto

2018-03-01

We consider the Sen limit of several global F-theory compactifications, some of which exhibit an MSSM-like spectrum. We show that these indeed have a consistent limit where they can be viewed as resulting from an intersecting brane configuration in type IIB. We discuss the match of the fluxes and the chiral spectrum in detail. We find that some D5-tadpole canceling gauge fluxes do not lift to harmonic vertical four-form fluxes in the resolved F-theory manifold. We discuss the connection between splitting of curves at weak coupling and remnant discrete symmetries.

Electrical stimulation of gut motility guided by an in silico model

NASA Astrophysics Data System (ADS)

Barth, Bradley B.; Henriquez, Craig S.; Grill, Warren M.; Shen, Xiling

2017-12-01

Objective. Neuromodulation of the central and peripheral nervous systems is becoming increasingly important for treating a diverse set of diseases—ranging from Parkinson’s Disease and epilepsy to chronic pain. However, neuromodulation of the gastrointestinal (GI) tract has achieved relatively limited success in treating functional GI disorders, which affect a significant population, because the effects of stimulation on the enteric nervous system (ENS) and gut motility are not well understood. Here we develop an integrated neuromechanical model of the ENS and assess neurostimulation strategies for enhancing gut motility, validated by in vivo experiments. Approach. The computational model included a network of enteric neurons, smooth muscle fibers, and interstitial cells of Cajal, which regulated propulsion of a virtual pellet in a model of gut motility. Main results. Simulated extracellular stimulation of ENS-mediated motility revealed that sinusoidal current at 0.5 Hz was more effective at increasing intrinsic peristalsis and reducing colon transit time than conventional higher frequency rectangular current pulses, as commonly used for neuromodulation therapy. Further analysis of the model revealed that the 0.5 Hz sinusoidal currents were more effective at modulating the pacemaker frequency of interstitial cells of Cajal. To test the predictions of the model, we conducted in vivo electrical stimulation of the distal colon while measuring bead propulsion in awake rats. Experimental results confirmed that 0.5 Hz sinusoidal currents were more effective than higher frequency pulses at enhancing gut motility. Significance. This work demonstrates an in silico GI neuromuscular model to enable GI neuromodulation parameter optimization and suggests that low frequency sinusoidal currents may improve the efficacy of GI pacing.

Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats

PubMed Central

Saha, Shyamali; Prakash, Satya

2014-01-01

The gut microbiota is a bacterial bioreactor whose composition is an asset for human health. However, circulating gut microbiota derived endotoxins cause metabolic endotoxemia, promoting metabolic and liver diseases. This study investigates the potential of orally delivered microencapsulated Bifidobacterium infantis ATCC 15697 to modulate the gut microbiota and reduce endotoxemia in F344 rats. The rats were gavaged daily with saline or microencapsulated B. infantis ATCC 15697. Following 38 days of supplementation, the treated rats showed a significant (P < 0.05) increase in fecal Bifidobacteria (4.34 ± 0.46 versus 2.45 ± 0.25% of total) and B. infantis (0.28 ± 0.21 versus 0.52 ± 0.12 % of total) and a significant (P < 0.05) decrease in fecal Enterobacteriaceae (0.80 ± 0.45 versus 2.83 ± 0.63% of total) compared to the saline control. In addition, supplementation with the probiotic formulation reduced fecal (10.52 ± 0.18 versus 11.29 ± 0.16 EU/mg; P = 0.01) and serum (0.33 ± 0.015 versus 0.30 ± 0.015 EU/mL; P = 0.25) endotoxins. Thus, microencapsulated B. infantis ATCC 15697 modulates the gut microbiota and reduces colonic and serum endotoxins. Future preclinical studies should investigate the potential of the novel probiotic formulation in metabolic and liver diseases. PMID:24967382

Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder

PubMed Central

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

2017-01-01

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. PMID:28349974

Effects of exposure to bisphenol A and ethinyl estradiol on the gut microbiota of parents and their offspring in a rodent model

PubMed Central

Javurek, Angela B.; Spollen, William G.; Johnson, Sarah A.; Bromert, Karen H.

2016-01-01

ABSTRACT Gut dysbiosis may result in various diseases, such as metabolic and neurobehavioral disorders. Exposure to endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE), especially during development, may also increase the risk for such disorders. An unexplored possibility is that EDC-exposure might alter the gut microbial composition. Gut flora and their products may thus be mediating factors for the disease-causing effects of these chemicals. To examine the effects of EDCs on the gut microbiome, female and male monogamous and biparental California mice (Peromyscus californicus) were exposed to BPA (50 mg/kg feed weight) or EE (0.1 ppb) or control diet from periconception through weaning. 16s rRNA sequencing was performed on bacterial DNA isolated from fecal samples, and analyses performed for P0 and F1 males and females. Both BPA and EE induced generational and sex-dependent gut microbiome changes. Many of the bacteria, e.g. Bacteroides, Mollicutes, Prevotellaceae, Erysipelotrichaceae, Akkermansia, Methanobrevibacter, Sutterella, whose proportions increase with exposure to BPA or EE in the P0 or F1 generation are associated with different disorders, such as inflammatory bowel disease (IBD), metabolic disorders, and colorectal cancer. However, the proportion of the beneficial bacterium, Bifidobacterium, was also elevated in fecal samples of BPA- and EE-exposed F1 females. Intestinal flora alterations were also linked to changes in various metabolic and other pathways. Thus, BPA and EE exposure may disrupt the normal gut flora, which may in turn result in systemic effects. Probiotic supplementation might be an effective means to mitigate disease-promoting effects of these chemicals. PMID:27624382

The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome

PubMed Central

Kelley, Scott T.; Skarra, Danalea V.; Rivera, Alissa J.; Thackray, Varykina G.

2016-01-01

Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet. PMID:26731268

Extension of loop quantum gravity to f(R) theories.

PubMed

Zhang, Xiangdong; Ma, Yongge

2011-04-29

The four-dimensional metric f(R) theories of gravity are cast into connection-dynamical formalism with real su(2) connections as configuration variables. Through this formalism, the classical metric f(R) theories are quantized by extending the loop quantization scheme of general relativity. Our results imply that the nonperturbative quantization procedure of loop quantum gravity is valid not only for general relativity but also for a rather general class of four-dimensional metric theories of gravity.

Microbial nutrient niches in the gut

PubMed Central

Pereira, Fátima C.

2017-01-01

Summary The composition and function of the mammalian gut microbiota has been the subject of much research in recent years, but the principles underlying the assembly and structure of this complex community remain incompletely understood. Processes that shape the gut microbiota are thought to be mostly niche‐driven, with environmental factors such as the composition of available nutrients largely determining whether or not an organism can establish. The concept that the nutrient landscape dictates which organisms can successfully colonize and persist in the gut was first proposed in Rolf Freter's nutrient niche theory. In a situation where nutrients are perfectly mixed and there is balanced microbial growth, Freter postulated that an organism can only survive if it is able to utilize one or a few limiting nutrients more efficiently than its competitors. Recent experimental work indicates, however, that nutrients in the gut vary in space and time. We propose that in such a scenario, Freter's nutrient niche theory must be expanded to account for the co‐existence of microorganisms utilizing the same nutrients but in distinct sites or at different times, and that metabolic flexibility and mixed‐substrate utilization are common strategies for survival in the face of ever‐present nutrient fluctuations. PMID:28035742

GUTs and TOEs

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

Lincoln, Don

2015-01-20

Albert Einstein said that what he wanted to know was “God’s thoughts,” which is a metaphor for the ultimate and most basic rules of the universe. Once known, all other phenomena would then be a consequence of these simple rules. While modern science is far from that goal, we have some thoughts on how this inquiry might unfold. In this video, Fermilab’s Dr. Don Lincoln tells what we know about GUTs (grand unified theories) and TOEs (theories of everything).

Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4.

PubMed

Peralta, Maria F; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

2017-01-01

Immunoglobulin Y (IgY) is the predominant antibody found in hen's ( Gallus domesticus ) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F 4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F 4 . Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F 4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F 4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer's patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing

Gut-Associated Lymphoid Tissue: A Key Tissue Inside the Mucosal Immune System of Hens Immunized with Escherichia coli F4

PubMed Central

Peralta, Maria F.; Magnoli, Alejandra; Alustiza, Fabrisio; Nilson, Armando; Miazzo, Raúl; Vivas, Adriana

2017-01-01

Immunoglobulin Y (IgY) is the predominant antibody found in hen’s (Gallus domesticus) egg yolk. This antibody, developed against several microorganisms in hen egg yolk, has been successfully used as an alternative to immunoglobulins from mammals for use in immunodiagnostics and immunotherapy. Enteropathogenic Escherichia coli (E.coli) F4 is the main etiological agent associated with swine neonatal diarrhea, and it causes notable economic losses in swine production. The aim of the present study was to evaluate the relationship between humoral immune response and the activation of gut-associated lymphoid tissue (GALT) in laying hens intramuscularly immunized with E. coli F4. Adult laying Shaver hens were immunized with a bacterin based on an inactivated lysate E. coli F4 strain that was originally isolated from neonatal piglet diarrhea, following a recommended schedule. The percentage of B lymphocytes in blood and spleen homogenates was determined by flow cytometry. Villi histomorphometry and the size of germinal centers (GC) activated in GALT and the spleen were measured in histological samples either stained with hematoxylin/eosin or through immunofluorescence. Antibody and isotype-specific antibodies in serum and egg yolk were measured using indirect enzyme-linked immunosorbent assay (ELISA). Secretory and serum immunoglobulin A (IgA) were measured by ELISA tests. Laying hen with intramuscular immunization with E. coli F4 lysate, activated both mucosal and systemic protection. Mucosal protection was provided through B lymphocytes, and most of them were activated on Peyer’s patches and esophageal tonsils, in GALT. Furthermore, increased B lymphocyte number in the lamina propria of the gut, and increased intraepithelial plasmatic cell number, produced high levels of mucosal IgA. Activated B lymphocytes interacted with absorptive cells, immune cells, and microbiota in the gut, producing signals that were translated into a powerful physical defense by producing a

Baryogenesis in nonminimally coupled f (R ) theories

NASA Astrophysics Data System (ADS)

Ramos, M. P. L. P.; Páramos, J.

2017-11-01

We generalize the mechanism for gravitational baryogensis in the context of f (R ) theories of gravity, including a nonminimal coupling between curvature and matter. In these models, the baryon asymmetry is generated through an effective coupling between the Ricci scalar curvature and the net baryon current that dynamically breaks Charge conjugation, parity and time reversal (C P T ) invariance. We study the combinations of characteristic mass scales and exponents for both nontrivial functions present in the modified action functional and establish the allowed region for these parameters: we find that very small deviations from general relativity are consistent with the observed baryon asymmetry and lead to temperatures compatible with the subsequent formation of the primordial abundances of light elements. In particular, we show the viability of a power-law nonminimal coupling function f2(R )˜Rn with 0

Gut Feelings as a Third Track in General Practitioners’ Diagnostic Reasoning

PubMed Central

Van de Wiel, Margje; Van Royen, Paul; Van Bokhoven, Marloes; Van der Weijden, Trudy; Dinant, Geert Jan

2010-01-01

Background General practitioners (GPs) are often faced with complicated, vague problems in situations of uncertainty that they have to solve at short notice. In such situations, gut feelings seem to play a substantial role in their diagnostic process. Qualitative research distinguished a sense of alarm and a sense of reassurance. However, not every GP trusted their gut feelings, since a scientific explanation is lacking. Objective This paper explains how gut feelings arise and function in GPs’ diagnostic reasoning. Approach The paper reviews literature from medical, psychological and neuroscientific perspectives. Conclusions Gut feelings in general practice are based on the interaction between patient information and a GP’s knowledge and experience. This is visualized in a knowledge-based model of GPs’ diagnostic reasoning emphasizing that this complex task combines analytical and non-analytical cognitive processes. The model integrates the two well-known diagnostic reasoning tracks of medical decision-making and medical problem-solving, and adds gut feelings as a third track. Analytical and non-analytical diagnostic reasoning interacts continuously, and GPs use elements of all three tracks, depending on the task and the situation. In this dual process theory, gut feelings emerge as a consequence of non-analytical processing of the available information and knowledge, either reassuring GPs or alerting them that something is wrong and action is required. The role of affect as a heuristic within the physician’s knowledge network explains how gut feelings may help GPs to navigate in a mostly efficient way in the often complex and uncertain diagnostic situations of general practice. Emotion research and neuroscientific data support the unmistakable role of affect in the process of making decisions and explain the bodily sensation of gut feelings.The implications for health care practice and medical education are discussed. PMID:20967509

Gut feelings as a third track in general practitioners' diagnostic reasoning.

PubMed

Stolper, Erik; Van de Wiel, Margje; Van Royen, Paul; Van Bokhoven, Marloes; Van der Weijden, Trudy; Dinant, Geert Jan

2011-02-01

General practitioners (GPs) are often faced with complicated, vague problems in situations of uncertainty that they have to solve at short notice. In such situations, gut feelings seem to play a substantial role in their diagnostic process. Qualitative research distinguished a sense of alarm and a sense of reassurance. However, not every GP trusted their gut feelings, since a scientific explanation is lacking. This paper explains how gut feelings arise and function in GPs' diagnostic reasoning. The paper reviews literature from medical, psychological and neuroscientific perspectives. Gut feelings in general practice are based on the interaction between patient information and a GP's knowledge and experience. This is visualized in a knowledge-based model of GPs' diagnostic reasoning emphasizing that this complex task combines analytical and non-analytical cognitive processes. The model integrates the two well-known diagnostic reasoning tracks of medical decision-making and medical problem-solving, and adds gut feelings as a third track. Analytical and non-analytical diagnostic reasoning interacts continuously, and GPs use elements of all three tracks, depending on the task and the situation. In this dual process theory, gut feelings emerge as a consequence of non-analytical processing of the available information and knowledge, either reassuring GPs or alerting them that something is wrong and action is required. The role of affect as a heuristic within the physician's knowledge network explains how gut feelings may help GPs to navigate in a mostly efficient way in the often complex and uncertain diagnostic situations of general practice. Emotion research and neuroscientific data support the unmistakable role of affect in the process of making decisions and explain the bodily sensation of gut feelings.The implications for health care practice and medical education are discussed.

Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

PubMed

Amato, Katherine R

2016-01-01

The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. © 2016 Wiley Periodicals, Inc.

Constraining f(R) theories with cosmography

NASA Astrophysics Data System (ADS)

Anabella Teppa Pannia, Florencia; Esteban Perez Bergliaffa, Santiago

2013-08-01

A method to set constraints on the parameters of extended theories of gravitation is presented. It is based on the comparison of two series expansions of any observable that depends on H(z). The first expansion is of the cosmographical type, while the second uses the dependence of H with z furnished by a given type of extended theory. When applied to f(R) theories together with the redshift drift, the method yields limits on the parameters of two examples (the theory of Hu and Sawicki [1], and the exponential gravity introduced by Linder [2]) that are compatible with or more stringent than the existing ones, as well as a limit for a previously unconstrained parameter.

Therapeutic effect of Tripterygium wilfordii Hook F multiglycosides on gut barrier dysfunction in rats with acute necrotizing pancreatitis.

PubMed

Wang, Jie; Wu, Gang; Ma, Baojin; Wu, Jianhua; Cai, Duan

2013-02-01

The aim of the current study was to investigate the therapeutic effect of Tripterygium wilfordii Hook F multiglycosides (TWG) on gut barrier dysfunction in rats with acute necrotizing pancreatitis (ANP). ANP was induced in rats using 3.5% sodium taurocholate. The rats were divided into 3 groups: the sham operation (SO), ANP and ANP+TWG groups. Biochemical and pathological change of pancreatic tissue and ileal mucosa, bacterial cultures and the survival rate were measured following surgery and treatment. TWG treatment significantly decreased amylase and lipase activities and plasma endotoxin and D-lactate levels. Edema and inflammation in the pancreas and ileal mucosa were alleviated. Positive bacterial cultures were significantly reduced. The survival rate of the rats in the ANP+TWG group was higher than that of the rats in the ANP group. TWG treatment showed beneficial effects by protecting the pancreas from bacterial infection caused by gut barrier dysfunction and improving the outcomes of the rats with ANP.

Observational information for f(T) theories and dark torsion

NASA Astrophysics Data System (ADS)

Bengochea, Gabriel R.

2011-01-01

In the present work we analyze and compare the information coming from different observational data sets in the context of a sort of f(T) theories. We perform a joint analysis with measurements of the most recent type Ia supernovae (SNe Ia), Baryon Acoustic Oscillation (BAO), Cosmic Microwave Background radiation (CMB), Gamma-Ray Bursts data (GRBs) and Hubble parameter observations (OHD) to constraint the only new parameter these theories have. It is shown that when the new combined BAO/CMB parameter is used to put constraints, the result is different from previous works. We also show that when we include Observational Hubble Data (OHD) the simpler ΛCDM model is excluded to one sigma level, leading the effective equation of state of these theories to be of phantom type. Also, analyzing a tension criterion for SNe Ia and other observational sets, we obtain more consistent and better suited data sets to work with these theories.

Depletion of Gut Microbiota Protects against Renal Ischemia-Reperfusion Injury

PubMed Central

Rampanelli, Elena; Stroo, Ingrid; Butter, Loes M.; Teske, Gwendoline J.; Claessen, Nike; Stokman, Geurt; Florquin, Sandrine; Leemans, Jaklien C.; Dessing, Mark C.

2017-01-01

An accumulating body of evidence shows that gut microbiota fulfill an important role in health and disease by modulating local and systemic immunity. The importance of the microbiome in the development of kidney disease, however, is largely unknown. To study this concept, we depleted gut microbiota with broad-spectrum antibiotics and performed renal ischemia-reperfusion (I/R) injury in mice. Depletion of the microbiota significantly attenuated renal damage, dysfunction, and remote organ injury and maintained tubular integrity after renal I/R injury. Gut flora–depleted mice expressed lower levels of F4/80 and chemokine receptors CX3CR1 and CCR2 in the F4/80+ renal resident macrophage population and bone marrow (BM) monocytes than did control mice. Additionally, compared with control BM monocytes, BM monocytes from gut flora–depleted mice had decreased migratory capacity toward CX3CL1 and CCL2 ligands. To study whether these effects were driven by depletion of the microbiota, we performed fecal transplants in antibiotic-treated mice and found that transplant of fecal material from an untreated mouse abolished the protective effect of microbiota depletion upon renal I/R injury. In conclusion, we show that depletion of gut microbiota profoundly protects against renal I/R injury by reducing maturation status of F4/80+ renal resident macrophages and BM monocytes. Therefore, dampening the inflammatory response by targeting microbiota-derived mediators might be a promising therapy against I/R injury. PMID:27927779

Predictions from a flavour GUT model combined with a SUSY breaking sector

NASA Astrophysics Data System (ADS)

Antusch, Stefan; Hohl, Christian

2017-10-01

We discuss how flavour GUT models in the context of supergravity can be completed with a simple SUSY breaking sector, such that the flavour-dependent (non-universal) soft breaking terms can be calculated. As an example, we discuss a model based on an SU(5) GUT symmetry and A 4 family symmetry, plus additional discrete "shaping symmetries" and a ℤ 4 R symmetry. We calculate the soft terms and identify the relevant high scale input parameters, and investigate the resulting predictions for the low scale observables, such as flavour violating processes, the sparticle spectrum and the dark matter relic density.

Time varying G and \\varLambda cosmology in f(R,T) gravity theory

NASA Astrophysics Data System (ADS)

Tiwari, R. K.; Beesham, A.; Singh, Rameshwar; Tiwari, L. K.

2017-08-01

We have studied the time dependence of the gravitational constant G and cosmological constant Λ by taking into account an anisotropic and homogeneous Bianchi type-I space-time in the framework of the modified f(R,T) theory of gravity proposed by Harko et al. (Phys. Rev. D 84:024020, 2011). For a specific choice of f(R,T)=R+2f(T) where f(T)=-λ T, two solutions of the modified gravity field equations have been generated with the help of a variation law between the expansion anisotropy ({σ}/{θ}) and the scale factor (S), together with a general non-linear equation of state. The solution for m≠3 corresponds to singular model of the universe whereas the solution for m=3 represents a non-singular model. We infer that the models entail a constant value of the deceleration parameter. A careful analysis of all the physical parameters of the models has also been carried out.

Microbial nutrient niches in the gut.

PubMed

Pereira, Fátima C; Berry, David

2017-04-01

The composition and function of the mammalian gut microbiota has been the subject of much research in recent years, but the principles underlying the assembly and structure of this complex community remain incompletely understood. Processes that shape the gut microbiota are thought to be mostly niche-driven, with environmental factors such as the composition of available nutrients largely determining whether or not an organism can establish. The concept that the nutrient landscape dictates which organisms can successfully colonize and persist in the gut was first proposed in Rolf Freter's nutrient niche theory. In a situation where nutrients are perfectly mixed and there is balanced microbial growth, Freter postulated that an organism can only survive if it is able to utilize one or a few limiting nutrients more efficiently than its competitors. Recent experimental work indicates, however, that nutrients in the gut vary in space and time. We propose that in such a scenario, Freter's nutrient niche theory must be expanded to account for the co-existence of microorganisms utilizing the same nutrients but in distinct sites or at different times, and that metabolic flexibility and mixed-substrate utilization are common strategies for survival in the face of ever-present nutrient fluctuations. © 2017 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

Spatiotemporal microbiota dynamics from quantitative in vitro and in silico models of the gut

NASA Astrophysics Data System (ADS)

Hwa, Terence

The human gut harbors a dynamic microbial community whose composition bears great importance for the health of the host. Here, we investigate how colonic physiology impacts bacterial growth behaviors, which ultimately dictate the gut microbiota composition. Combining measurements of bacterial growth physiology with analysis of published data on human physiology into a quantitative modeling framework, we show how hydrodynamic forces in the colon, in concert with other physiological factors, determine the abundances of the major bacterial phyla in the gut. Our model quantitatively explains the observed variation of microbiota composition among healthy adults, and predicts colonic water absorption (manifested as stool consistency) and nutrient intake to be two key factors determining this composition. The model further reveals that both factors, which have been identified in recent correlative studies, exert their effects through the same mechanism: changes in colonic pH that differentially affect the growth of different bacteria. Our findings show that a predictive and mechanistic understanding of microbial ecology in the human gut is possible, and offer the hope for the rational design of intervention strategies to actively control the microbiota. This work is supported by the Bill and Melinda Gates Foundation.

Towards a complete Δ(27) × SO(10) GUT of flavour

NASA Astrophysics Data System (ADS)

Björkeroth, Fredrik

2017-09-01

We propose a renormalisable model based on Δ(27) family symmetry with an SO(10) grand unified theory (GUT) leading to a novel form of spontaneous geometrical CP violation. The symmetries are broken close to the GUT breaking scale to yield the minimal supersymmetric standard model with standard R-parity. Low-scale Yukawa structure is dictated by the coupling of matter to Δ(27) antitriplets \\bar φ whose vacuum expectation values are aligned in the CSD3 directions by the superpotential. Light physical Majorana neutrinos masses emerge from the seesaw mechanism within SO(10). The model predicts a normal neutrino mass hierarchy with the best-fit lightest neutrino mass m 1 ∼ 0.3 meV, CP-violating oscillation phase δl ≈ 280° and the remaining neutrino parameters all within 1σ of their best-fit experimental values.

GUTs and TOEs

ScienceCinema

Lincoln, Don

2018-01-16

Albert Einstein said that what he wanted to know was “God’s thoughts,” which is a metaphor for the ultimate and most basic rules of the universe. Once known, all other phenomena would then be a consequence of these simple rules. While modern science is far from that goal, we have some thoughts on how this inquiry might unfold. In this video, Fermilab’s Dr. Don Lincoln tells what we know about GUTs (grand unified theories) and TOEs (theories of everything).

Cosmological bound from the neutron star merger GW170817 in scalar-tensor and F(R) gravity theories

NASA Astrophysics Data System (ADS)

Nojiri, Shin'ichi; Odintsov, Sergei D.

2018-04-01

We consider the evolution of cosmological gravitational waves in scalar-tensor theory and F (R) gravity theory as typical models of the modified gravity. Although the propagation speed is not changed from the speed of light, the propagation phase changes when we compare the propagation in these modified gravity theories with the propagation in the ΛCDM model. The phase change might be detected in future observations.

Algorithmic universality in F-theory compactifications

NASA Astrophysics Data System (ADS)

Halverson, James; Long, Cody; Sung, Benjamin

2017-12-01

We study universality of geometric gauge sectors in the string landscape in the context of F-theory compactifications. A finite time construction algorithm is presented for 4/3 ×2.96 ×10755 F-theory geometries that are connected by a network of topological transitions in a connected moduli space. High probability geometric assumptions uncover universal structures in the ensemble without explicitly constructing it. For example, non-Higgsable clusters of seven-branes with intricate gauge sectors occur with a probability above 1 - 1.01 ×10-755 , and the geometric gauge group rank is above 160 with probability 0.999995. In the latter case there are at least 10 E8 factors, the structure of which fixes the gauge groups on certain nearby seven-branes. Visible sectors may arise from E6 or S U (3 ) seven-branes, which occur in certain random samples with probability ≃1 /200 .

New holographic dark energy model with constant bulk viscosity in modified f(R,T) gravity theory

NASA Astrophysics Data System (ADS)

Srivastava, Milan; Singh, C. P.

2018-06-01

The aim of this paper is to study new holographic dark energy (HDE) model in modified f(R,T) gravity theory within the framework of a flat Friedmann-Robertson-Walker model with bulk viscous matter content. It is thought that the negative pressure caused by the bulk viscosity can play the role of dark energy component, and drive the accelerating expansion of the universe. This is the motive of this paper to observe such phenomena with bulk viscosity. In the specific model f(R,T)=R+λ T, where R is the Ricci scalar, T the trace of the energy-momentum tensor and λ is a constant, we find the solution for non-viscous and viscous new HDE models. We analyze new HDE model with constant bulk viscosity, ζ =ζ 0= const. to explain the present accelerated expansion of the universe. We classify all possible scenarios (deceleration, acceleration and their transition) with possible positive and negative ranges of λ over the constraint on ζ 0 to analyze the evolution of the universe. We obtain the solutions of scale factor and deceleration parameter, and discuss the evolution of the universe. We observe the future finite-time singularities of type I and III at a finite time under certain constraints on λ . We also investigate the statefinder and Om diagnostics of the viscous new HDE model to discriminate with other existing dark energy models. In late time the viscous new HDE model approaches to Λ CDM model. We also discuss the thermodynamics and entropy of the model and find that it satisfies the second law of thermodynamics.

A bidirectional association between the gut microbiota and CNS disease in a biphasic murine model of multiple sclerosis.

PubMed

Colpitts, Sara L; Kasper, Eli J; Keever, Abigail; Liljenberg, Caleb; Kirby, Trevor; Magori, Krisztian; Kasper, Lloyd H; Ochoa-Repáraz, Javier

2017-11-02

The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive multiple sclerosis (SP-MS). This non-obese diabetic (NOD) model of EAE develops a biphasic pattern of disease that more closely resembles the human condition when transitioning from relapsing-remitting (RR)-MS to SP-MS. We compared the gut microbiome of NOD mice with either mild or severe disease to that of non-immunized control mice. We found that the mice which developed a severe secondary form of EAE harbored a dysbiotic gut microbiome when compared with the healthy control mice. Furthermore, we evaluated whether treatment with a cocktail of broad-spectrum antibiotics would modify the outcome of the progressive stage of EAE in the NOD model. Our results indicated reduced mortality and clinical disease severity in mice treated with antibiotics compared with untreated mice. Our findings support the hypothesis that there are reciprocal effects between experimental CNS inflammatory demyelination and modification of the microbiome providing a foundation for the establishment of early therapeutic interventions targeting the gut microbiome that could potentially limit disease progression.

Constraint on reconstructed f(R) gravity models from gravitational waves

NASA Astrophysics Data System (ADS)

Lee, Seokcheon

2018-06-01

The gravitational wave (GW) detection of a binary neutron star inspiral made by the Advanced LIGO and Advanced Virgo paves the unprecedented way for multi-messenger observations. The propagation speed of this GW can be scrutinized by comparing the arrival times between GW and neutrinos or photons. It provides the constraint on the mass of the graviton. f(R) gravity theories have the habitual non-zero mass gravitons in addition to usual massless ones. Previously, we show that the model independent f(R) gravity theories can be constructed from the both background evolution and the matter growth with one undetermined parameter. We show that this parameter can be constrained from the graviton mass bound obtained from GW detection. Thus, the GW detection provides the invaluable constraint on the validity of f(R) gravity theories.

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

Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer's Mouse Model.

PubMed

Brandscheid, Carolin; Schuck, Florian; Reinhardt, Sven; Schäfer, Karl-Herbert; Pietrzik, Claus U; Grimm, Marcus; Hartmann, Tobias; Schwiertz, Andreas; Endres, Kristina

2017-01-01

The regulation of physiological gut functions such as peristalsis or secretion of digestive enzymes by the central nervous system via the Nervus vagus is well known. Recent investigations highlight that pathological conditions of neurological or psychiatric disorders might directly interfere with the autonomous neuronal network of the gut - the enteric nervous system, or even derive from there. By using a murine Alzheimer's disease model, we investigated a potential influence of disease-associated changes on gastrointestinal properties. 5xFAD mice at three different ages were compared to wild type littermates in regard to metabolic parameters and enzymes of the gut by fluorimetric enzyme assay and western blotting. Overexpression of human amyloid-β protein precursor (AβPP) within the gut was assessed by qPCR and IHC; fecal microbiome analysis was conducted by 16SrRNA quantitation of selected phyla and species. While general composition of fecal samples, locomotion, and food consumption of male 5xFAD animals were not changed, we observed a reduced body weight occurring at early pathological stages. Human AβPP was not only expressed within the brain of these mice but also in gut tissue. Analysis of fecal proteins revealed a reduced trypsin amount in the 5xFAD model mice as compared to the wild type. In addition, we observed changes in fecal microbiota composition along with age. We therefore suggest that the presence of the mutated transgenes (AβPP and PS1), which are per se the basis for the genetic form of Alzheimer's disease in humans, directly interferes with gut function as shown here for the disease model mice.

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.

The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation.

PubMed

Schrumpf, Elisabeth; Kummen, Martin; Valestrand, Laura; Greiner, Thomas U; Holm, Kristian; Arulampalam, Velmurugesan; Reims, Henrik M; Baines, John; Bäckhed, Fredrik; Karlsen, Tom H; Blumberg, Richard S; Hov, Johannes R; Melum, Espen

2017-02-01

A strong association between human inflammatory biliary diseases and gut inflammation has led to the hypothesis that gut microbes and lymphocytes activated in the intestine play a role in biliary inflammation. The NOD.c3c4 mouse model develops spontaneous biliary inflammation in extra- and intrahepatic bile ducts. We aimed to clarify the role of the gut microbiota in the biliary disease of NOD.c3c4 mice. We sampled cecal content and mucosa from conventionally raised (CONV-R) NOD.c3c4 and NOD control mice, extracted DNA and performed 16S rRNA sequencing. NOD.c3c4 mice were rederived into a germ free (GF) facility and compared with CONV-R NOD.c3c4 mice. NOD.c3c4 mice were also co-housed with NOD mice and received antibiotics from weaning. The gut microbial profiles of mice with and without biliary disease were different both before and after rederivation (unweighted UniFrac-distance). GF NOD.c3c4 mice had less distended extra-hepatic bile ducts than CONV-R NOD.c3c4 mice, while antibiotic treated mice showed reduction of biliary infarcts. GF animals also showed a reduction in liver weight compared with CONV-R NOD.c3c4 mice, and this was also observed in antibiotic treated NOD.c3c4 mice. Co-housing of NOD and NOD.c3c4 mice indicated that the biliary phenotype was neither transmissible nor treatable by co-housing with healthy mice. NOD.c3c4 and NOD control mice show marked differences in the gut microbiota. GF NOD.c3c4 mice develop a milder biliary affection compared with conventionally raised NOD.c3c4 mice. Our findings suggest that the intestinal microbiota contributes to disease in this murine model of biliary inflammation. Mice with liver disease have a gut microflora (microbiota) that differs substantially from normal mice. In a normal environment, these mice spontaneously develop disease in their bile ducts. However, when these mice, are raised in an environment devoid of bacteria, the disease in the bile ducts diminishes. Overall this clearly indicates that the

A comparative evaluation of models to predict human intestinal metabolism from nonclinical data

PubMed Central

Yau, Estelle; Petersson, Carl; Dolgos, Hugues

2017-01-01

Abstract Extensive gut metabolism is often associated with the risk of low and variable bioavailability. The prediction of the fraction of drug escaping gut wall metabolism as well as transporter‐mediated secretion (F g) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate F g and, based on the outcome, to provide recommendations for the prediction of human F g during drug discovery and early drug development. The use of in vitro intrinsic clearance from human liver microsomes (HLM) in three mechanistic models – the ADAM, Q gut and Competing Rates – was evaluated for drugs whose metabolism is dominated by CYP450s, assuming that the effect of transporters is negligible. The utility of rat as a model for human F g was also explored. The ADAM, Q gut and Competing Rates models had comparable prediction success (70%, 74%, 69%, respectively) and bias (AFE = 1.26, 0.74 and 0.81, respectively). However, the ADAM model showed better accuracy compared with the Q gut and Competing Rates models (RMSE =0.20 vs 0.30 and 0.25, respectively). Rat is not a good model (prediction success =32%, RMSE =0.48 and AFE = 0.44) as it seems systematically to under‐predict human F g. Hence, we would recommend the use of rat to identify the need for F g assessment, followed by the use of HLM in simple models to predict human F g. © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd. PMID:28152562

Stellar structure model in hydrostatic equilibrium in the context of f({\\mathscr{R}})-gravity

NASA Astrophysics Data System (ADS)

André, Raíla; Kremer, Gilberto M.

2017-12-01

In this work we present a stellar structure model from the f({\\mathscr{R}})-gravity point of view capable of describing some classes of stars (white dwarfs, brown dwarfs, neutron stars, red giants and the Sun). This model is based on f({\\mathscr{R}})-gravity field equations for f({\\mathscr{R}})={\\mathscr{R}}+{f}2{{\\mathscr{R}}}2, hydrostatic equilibrium equation and a polytropic equation of state. We compare the results obtained with those found by Newtonian theory. It has been observed that in these systems, where high curvature regimes emerge, stellar structure equations undergo modifications. Despite the simplicity of this model, the results are satisfactory. The estimated values of pressure, density and temperature of the stars are within those determined by observations. This f({\\mathscr{R}})-gravity model has proved to be necessary to describe stars with strong fields such as white dwarfs, neutron stars and brown dwarfs, while stars with weaker fields, such as red giants and the Sun, are best described by Newtonian theory.

Simulation for F.C.C. deformation texture by modified pencil glide theory[Face Centered Cubic

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

Masui, H.

1999-11-26

Inspired by the pencil glide theory for b.c.c. metal, modified pencil glide theory for f.c.c. metal was proposed, dividing the 12 glide systems of f.c.c. metal into three groups individually composed of eight {l{underscore}brace}111{r{underscore}brace}{l{underscore}angle}110{r{underscore}angle} glide systems around the principal axes X[100], Y[010] and Z[001]. These assumptions yielded two mathematical solutions {Omega}(3) and {Omega}(1). In {Omega}(3), from the three groups with four complete conjugated glide systems composed of, respectively, two glide systems of common {l{underscore}angle}110{r{underscore}angle} direction, only one group with the maximum plastic work may operate if the requirements are satisfied, otherwise glide systems in {Omega}(1) where one of the fourmore » conjugated glide systems is zero are activated. The model considering the 12 glide systems of f.c.c. as a whole explained many experimentally stable orientations in axisymmetric and rolling deformation. The differences between the two pencil glide theories for b.c.c. and f.c.c. are also discussed with data.« less

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

Anisotropy effects on baryogenesis in f(R) theories of gravity

NASA Astrophysics Data System (ADS)

Aghamohammadi, A.; Hossienkhani, H.; Saaidi, Kh.

2018-04-01

We study the f(R) theory of gravity in an anisotropic metric and its effect on the baryon number-to-entropy ratio. The mechanism of gravitational baryogenesis based on the CPT-violating gravitational interaction between derivative of the Ricci scalar curvature and the baryon-number current is investigated in the context of the f(R) gravity. The gravitational baryogenesis in the Bianchi type I (BI) Universe is examined. We survey the effect of anisotropy of the Universe on the baryon asymmetry from the point of view of the f(R) theories of gravity and its effect on nb/s for radiation dominant regime.

A framework for the modeling of gut blood flow regulation and postprandial hyperaemia

PubMed Central

Jeays, Adam David; Lawford, Patricia Veronica; Gillott, Richard; Spencer, Paul A; Bardhan, Karna Dev; Hose, David Rodney

2007-01-01

After a meal the activity of the gut increases markedly as digestion takes place. Associated with this increase in activity is an increase in blood flow, which has been shown to be dependent on factors such as caloric content and constitution of the meal. Much qualitative work has been carried out regarding mechanisms for the presence of food in a section of gut producing increased blood flow to that section, but there are still many aspects of this process that are not fully understood. In this paper we briefly review current knowledge on several relevant areas relating to gut blood flow, focusing on quantitative data where available and highlighting areas where further research is needed. We then present new data on the effect of feeding on flow in the superior mesenteric artery. Finally, we describe a framework for combining this data to produce a single model describing the mechanisms involved in postprandial hyperaemia. For a section of the model, where appropriate data are available, preliminary results are presented. PMID:17457971

Density-functional theory applied to d- and f-electron systems

NASA Astrophysics Data System (ADS)

Wu, Xueyuan

Density functional theory (DFT) has been applied to study the electronic and geometric structures of prototype d- and f-electron systems. For the d-electron system, all electron DFT with gradient corrections to the exchange and correlation functionals has been used to investigate the properties of small neutral and cationic vanadium clusters. Results are in good agreement with available experimental and other theoretical data. For the f-electron system, a hybrid DFT, namely, B3LYP (Becke's 3-parameter hybrid functional using the correlation functional of Lee, Yang and Parr) with relativistic effective core potentials and cluster models has been applied to investigate the nature of chemical bonding of both the bulk and the surfaces of plutonium monoxide and dioxide. Using periodic models, the electronic and geometric structures of PuO2 and its (110) surface, as well as water adsorption on this surface have also been investigated using DFT in both local density approximation (LDA) and generalized gradient approximation (GGA) formalisms.

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 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

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.

A comparative evaluation of models to predict human intestinal metabolism from nonclinical data.

PubMed

Yau, Estelle; Petersson, Carl; Dolgos, Hugues; Peters, Sheila Annie

2017-04-01

Extensive gut metabolism is often associated with the risk of low and variable bioavailability. The prediction of the fraction of drug escaping gut wall metabolism as well as transporter-mediated secretion (F g ) has been challenged by the lack of appropriate preclinical models. The purpose of this study is to compare the performance of models that are widely employed in the pharmaceutical industry today to estimate F g and, based on the outcome, to provide recommendations for the prediction of human F g during drug discovery and early drug development. The use of in vitro intrinsic clearance from human liver microsomes (HLM) in three mechanistic models - the ADAM, Q gut and Competing Rates - was evaluated for drugs whose metabolism is dominated by CYP450s, assuming that the effect of transporters is negligible. The utility of rat as a model for human F g was also explored. The ADAM, Q gut and Competing Rates models had comparable prediction success (70%, 74%, 69%, respectively) and bias (AFE = 1.26, 0.74 and 0.81, respectively). However, the ADAM model showed better accuracy compared with the Q gut and Competing Rates models (RMSE =0.20 vs 0.30 and 0.25, respectively). Rat is not a good model (prediction success =32%, RMSE =0.48 and AFE = 0.44) as it seems systematically to under-predict human F g . Hence, we would recommend the use of rat to identify the need for F g assessment, followed by the use of HLM in simple models to predict human F g . © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd. © 2017 Merck KGaA. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd.

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.

Towards an integrated understanding of gut microbiota using insects as model systems.

PubMed

Pernice, Mathieu; Simpson, Stephen J; Ponton, Fleur

2014-10-01

Metazoans form symbioses with microorganisms that synthesize essential nutritional compounds and increase their efficiency to digest and absorb nutrients. Despite the growing awareness that microbes within the gut play key roles in metabolism, health and development of metazoans, symbiotic relationships within the gut are far from fully understood. Insects, which generally harbor a lower microbial diversity than vertebrates, have recently emerged as potential model systems to study these interactions. In this review, we give a brief overview of the characteristics of the gut microbiota in insects in terms of low diversity but high variability at intra- and interspecific levels and we investigate some of the ecological and methodological factors that might explain such variability. We then emphasize how studies integrating an array of techniques and disciplines have the potential to provide new understanding of the biology of this micro eco-system. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

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

Generalized second law of thermodynamics in f(R,T) theory of gravity

NASA Astrophysics Data System (ADS)

Momeni, D.; Moraes, P. H. R. S.; Myrzakulov, R.

2016-07-01

We present a study of the generalized second law of thermodynamics in the scope of the f(R,T) theory of gravity, with R and T representing the Ricci scalar and trace of the energy-momentum tensor, respectively. From the energy-momentum tensor equation for the f(R,T)=R+f(T) case, we calculate the form of the geometric entropy in such a theory. Then, the generalized second law of thermodynamics is quantified and some relations for its obedience in f(R,T) gravity are presented. Those relations depend on some cosmological quantities, as the Hubble and deceleration parameters, and also on the form of f(T).

Diphoton resonance in F-theory inspired flipped SO(10)

NASA Astrophysics Data System (ADS)

Leontaris, George K.; Shafi, Qaisar

2016-10-01

Motivated by the di-photon excess at 750 GeV reported by the ATLAS and CMS experiments, we present an F-theory inspired flipped SO(10) model embedded in E_6. The low energy spectrum includes the three MSSM chiral families, vector-like colour triplets, several pairs of charged SU(2)_L singlet fields (E^c, bar{E}^c), as well as MSSM singlets, one or more of which could contribute to the di-photon resonance. A total decay width in the multi-GeV range can arise from couplings involving the singlet and MSSM fields.

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

Kaluza-Klein cosmological model in f(R, T) gravity with Λ(T)

NASA Astrophysics Data System (ADS)

Sahoo, P. K.; Mishra, B.; Tripathy, S. K.

2016-04-01

A class of Kaluza-Klein cosmological models in $f(R,T)$ theory of gravity have been investigated. In the work, we have considered the functional $f(R,T)$ to be in the form $f(R,T)=f(R)+f(T)$ with $f(R)=\\lambda R$ and $f(T)=\\lambda T$. Such a choice of the functional $f(R,T)$ leads to an evolving effective cosmological constant $\\Lambda$ which depends on the stress energy tensor. The source of the matter field is taken to be a perfect cosmic fluid. The exact solutions of the field equations are obtained by considering a constant deceleration parameter which leads two different aspects of the volumetric expansion namely a power law and an exponential volumetric expansion. Keeping an eye on the accelerating nature of the universe in the present epoch, the dynamics and physical behaviour of the models have been discussed. From statefinder diagnostic pair we found that the model with exponential volumetric expansion behaves more like a $\\Lambda$CDM model.

Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.

PubMed

Spychala, Monica S; Venna, Venugopal Reddy; Jandzinski, Michal; Doran, Sarah J; Durgan, David J; Ganesh, Bhanu Priya; Ajami, Nadim J; Putluri, Nagireddy; Graf, Joerg; Bryan, Robert M; McCullough, Louise D

2018-05-07

Objective Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation. Methods Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke. Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke. Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG). Mice were subjected to ischemic stroke (MCAO) or sham surgery. During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S rRNA analysis of bacterial content. Results We found that the microbiota is altered after experimental stroke in young mice, and resembles the biome of uninjured aged mice. In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased ∼9-fold (P<0.001) compared to young. This increased F:B ratio in aged mice is indicative of dysbiosis. Altering the microbiota in young by fecal gavage to resemble that of aged mice (∼6-fold increase in F:B ratio, P<0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels. Conversely, altering the microbiota in aged to resemble that of young (∼9-fold decrease in F:B ratio, P<0.001) increased survival and improved recovery following MCAO. Interpretation Aged biome increased the levels of systemic pro-inflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age-related diseases. This article is protected by copyright. All rights reserved. © 2018 American Neurological Association.

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.

Towards predictive models of the human gut microbiome

PubMed Central

2014-01-01

The intestinal microbiota is an ecosystem susceptible to external perturbations such as dietary changes and antibiotic therapies. Mathematical models of microbial communities could be of great value in the rational design of microbiota-tailoring diets and therapies. Here, we discuss how advances in another field, engineering of microbial communities for wastewater treatment bioreactors, could inspire development of mechanistic mathematical models of the gut microbiota. We review the current state-of-the-art in bioreactor modeling and current efforts in modeling the intestinal microbiota. Mathematical modeling could benefit greatly from the deluge of data emerging from metagenomic studies, but data-driven approaches such as network inference that aim to predict microbiome dynamics without explicit mechanistic knowledge seem better suited to model these data. Finally, we discuss how the integration of microbiome shotgun sequencing and metabolic modeling approaches such as flux balance analysis may fulfill the promise of a mechanistic model of the intestinal microbiota. PMID:24727124

Dynamically SUSY breaking SQCD on F-theory seven-branes

NASA Astrophysics Data System (ADS)

Buchbinder, Evgeny I.

2008-09-01

We study how dynamically breaking SQCD can be obtained on two intersecting seven-branes in F-theory. In the mechanism which we present in this paper one of the seven-branes is responsible for producing the low-energy gauge group and the other one is for generating vector bundle moduli. The fundamental matter charged under the gauge group is localized on the intersection. The mass of the matter fields is controlled by the vector bundle moduli. The analysis of under what conditions a sufficient number of the fundamental flavors becomes light turns out to be equivalent to the analysis of non-perturbative superpotentials for vector bundle moduli in Heterotic M-theory. We give an example in which we present an explicit equation in the moduli space whose zero locus corresponds to the fundamental fields becoming light. This allows us to provide a local F-theory realization of massive Script N = 1, SU(Nc) SQCD in the free magnetic range which dynamically breaks supersymmetry.

Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism.

PubMed

Hoek, Milan J A van; Merks, Roeland M H

2017-05-16

The human gut contains approximately 10 14 bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. In this model, cross-feeding interactions emerge readily, despite the species' ability to metabolize sugars autonomously. Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea. In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall.

An agent-based modeling framework for evaluating hypotheses on risks for developing autism: effects of the gut microbial environment.

PubMed

Weston, Bronson; Fogal, Benjamin; Cook, Daniel; Dhurjati, Prasad

2015-04-01

The number of cases diagnosed with Autism Spectrum Disorders is rising at an alarming rate with the Centers for Disease Control estimating the 2014 incidence rate as 1 in 68. Recently, it has been hypothesized that gut bacteria may contribute to the development of autism. Specifically, the relative balances between the inflammatory microbes clostridia and desulfovibrio and the anti-inflammatory microbe bifidobacteria may become destabilized prior to autism development. The imbalance leads to a leaky gut, characterized by a more porous epithelial membrane resulting in microbial toxin release into the blood, which may contribute to brain inflammation and autism development. To test how changes in population dynamics of the gut microbiome may lead to the imbalanced microbial populations associated with autism patients, we constructed a novel agent-based model of clostridia, desulfovibrio, and bifidobacteria population interactions in the gut. The model demonstrates how changing physiological conditions in the gut can affect the population dynamics of the microbiome. Simulations using our agent-based model indicate that despite large perturbations to initial levels of bacteria, the populations robustly achieve a single steady-state given similar gut conditions. These simulation results suggests that disturbance such as a prebiotic or antibiotic treatment may only transiently affect the gut microbiome. However, sustained prebiotic treatments may correct low population counts of bifidobacteria. Furthermore, our simulations suggest that clostridia growth rate is a key determinant of risk of autism development. Treatment of high-risk infants with supra-physiological levels of lysozymes may suppress clostridia growth rate, resulting in a steep decrease in the clostridia population and therefore reduced risk of autism development. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Renormalization group naturalness of GUT Higgs potentials

NASA Astrophysics Data System (ADS)

Allanach, B. C.; Amelino-Camelia, G.; Philipsen, O.; Pisanti, O.; Rosa, L.

1999-01-01

We analyze the symmetry-breaking patterns of grand unified theories from the point of view of a recently proposed criterion of renormalization-group naturalness. We perform the analysis on simple non-SUSY SU(5) and SO(10) and SUSY SU(5) GUTs. We find that the naturalness criterion can favor spontaneous symmetry breaking in the direction of the smallest of the maximal little groups. Some differences between theories with and without supersymmetry are also emphasized.

Sneutrino driven GUT inflation in supergravity

NASA Astrophysics Data System (ADS)

Gonzalo, Tomás E.; Heurtier, Lucien; Moursy, Ahmad

2017-06-01

In this paper, we embed the model of flipped GUT sneutrino inflation — in a flipped SU(5) or SO(10) set up — developed by Ellis et al. in a supergravity framework. The GUT symmetry is broken by a waterfall which could happen at early or late stage of the inflationary period. The full field dynamics is thus studied in detail and these two main inflationary configurations are exposed, whose cosmological predictions are both in agreement with recent astrophysical measurements. The model has an interesting feature where the inflaton has natural decay channels to the MSSM particles allowed by the GUT gauge symmetry. Hence it can account for the reheating after the inflationary epoch.

Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection.

PubMed

Crowther, Grace S; Baines, Simon D; Todhunter, Sharie L; Freeman, Jane; Chilton, Caroline H; Wilcox, Mark H

2013-01-01

First-line treatment options for Clostridium difficile infection (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the treatment of CDI. We compared the responses to NVB302 and vancomycin when used to treat simulated CDI in an in vitro gut model. We used ceftriaxone to elicit simulated CDI in an in vitro gut model primed with human faeces. Vancomycin and NVB302 were instilled into separate gut models and the indigenous gut microbiota and C. difficile total viable counts, spores and toxin levels were monitored throughout. Ceftriaxone instillation promoted C. difficile germination and high-level toxin production. Commencement of NVB302 and vancomycin instillation reduced C. difficile total viable counts rapidly with only C. difficile spores remaining within 3 and 4 days, respectively. Cytotoxin was reduced to undetectable levels 5 and 7 days after vancomycin and NVB302 instillation commenced in vessel 2 and 3, respectively, and remained undetectable for the remainder of the experiments. C. difficile spores were unaffected by the presence of vancomycin or NVB302. NVB302 treatment was associated with faster resolution of Bacteroides fragilis group. Both NVB302 and vancomycin were effective in treating simulated CDI in an in vitro gut model. C. difficile spore recrudescence was not observed following successful treatment with either NVB302 or vancomycin. NVB302 displayed non-inferiority to vancomycin in the treatment of simulated CDI, and had less deleterious effects against B. fragilis group. NVB302 warrants further clinical investigation as a potentially novel antimicrobial agent for the treatment of CDI.

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.

Perinatal Programming of Asthma: The Role of Gut Microbiota

PubMed Central

Azad, Meghan B.; Kozyrskyj, Anita L.

2012-01-01

Perinatal programming, a dominant theory for the origins of cardiovascular disease, proposes that environmental stimuli influence developmental pathways during critical periods of prenatal and postnatal development, inducing permanent changes in metabolism. In this paper, we present evidence for the perinatal programming of asthma via the intestinal microbiome. While epigenetic mechanisms continue to provide new explanations for the programming hypothesis of asthma development, it is increasingly apparent that the intestinal microbiota plays an independent and potentially interactive role. Commensal gut bacteria are essential to immune system development, and exposures disrupting the infant gut microbiota have been linked to asthma. This paper summarizes the recent findings that implicate caesarean delivery, breastfeeding, perinatal stress, probiotics, and antibiotics as modifiers of infant gut microbiota in the development of asthma. PMID:22110540

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

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.

Yukawa unification in an SO(10) SUSY GUT: SUSY on the edge

NASA Astrophysics Data System (ADS)

Poh, Zijie; Raby, Stuart

2015-07-01

In this paper we analyze Yukawa unification in a three family SO(10) SUSY GUT. We perform a global χ2 analysis and show that supersymmetry (SUSY) effects do not decouple even though the universal scalar mass parameter at the grand unified theory (GUT) scale, m16, is found to lie between 15 and 30 TeV with the best fit given for m16≈25 TeV . Note, SUSY effects do not decouple since stops and bottoms have mass of order 5 TeV, due to renormalization group running from MGUT. The model has many testable predictions. Gauginos are the lightest sparticles and the light Higgs boson is very much standard model-like. The model is consistent with flavor and C P observables with the BR (μ →e γ ) close to the experimental upper bound. With such a large value of m16 we clearly cannot be considered "natural" SUSY nor are we "split" SUSY. We are thus in the region in between or "SUSY on the edge."

Efficacy of surotomycin in an in vitro gut model of Clostridium difficile infection.

PubMed

Chilton, C H; Crowther, G S; Todhunter, S L; Nicholson, S; Freeman, J; Chesnel, L; Wilcox, M H

2014-09-01

We investigated the efficacy of the cyclic lipopeptide surotomycin in treating clindamycin-induced Clostridium difficile infection (CDI) using an in vitro gut model. Two three-stage chemostat gut models were inoculated with human faeces, spiked with C. difficile spores (∼10(7) cfu/mL, PCR ribotype 027 or 001). Clindamycin (33.9 mg/L, four times daily for 7 days) was dosed to induce CDI. Following high-level toxin production, surotomycin (250 mg/L, twice daily for 7 days) was instilled. Microflora populations, C. difficile vegetative cells and spores, cytotoxin titres and antimicrobial levels (LC-MS/MS and bioassay) were determined. The emergence of C. difficile and enterococci with reduced susceptibility to surotomycin was monitored on breakpoint agar (4 × MIC). Counts of viable C. difficile were reduced to near the limit of detection on Days 1 and 3 of surotomycin instillation, and cytotoxin was undetectable on Days 3 and 4 of surotomycin instillation in the 027 and 001 models, respectively. Recurrence of vegetative growth and toxin production occurred 11 days (001 model) and 15 days (027 model) after surotomycin instillation had ceased, and remained for the duration of the experiment. Surotomycin instillation decreased populations of bifidobacteria, clostridia, enterococci and lactobacilli, but was sparing of Bacteroides fragilis group populations. All enumerated organisms had recovered to steady-state levels by 3 weeks post-surotomycin instillation. No evidence of the emergence of reduced susceptibility to surotomycin was observed. Surotomycin successfully reduced C. difficile vegetative cell counts and toxin levels in the gut model and was sparing of B. fragilis group populations. There was no evidence of decreased susceptibility to surotomycin during exposure or post-exposure. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e

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.

Hamiltonian formulation of Palatini f(R) theories a la Brans-Dicke theory

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

Olmo, Gonzalo J.; Sanchis-Alepuz, Helios; Institut fuer Physik, Karl-Franzens-Universitaet Graz

2011-05-15

We study the Hamiltonian formulation of f(R) theories of gravity both in metric and in Palatini formalism using their classical equivalence with Brans-Dicke theories with a nontrivial potential. The Palatini case, which corresponds to the {omega}=-3/2 Brans-Dicke theory, requires special attention because of new constraints associated with the scalar field, which is nondynamical. We derive, compare, and discuss the constraints and evolution equations for the {omega}=-3/2 and {omega}{ne}-3/2 cases. Based on the properties of the constraint and evolution equations, we find that, contrary to certain claims in the literature, the Cauchy problem for the {omega}=-3/2 case is well formulated andmore » there is no reason to believe that it is not well posed in general.« less

Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

PubMed Central

van den Hoogen, Ward J.; Laman, Jon D.; ’t Hart, Bert A.

2017-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research. PMID:28928747

A NOTE ON THE UNIFIED FIRST LAW IN f(R) GRAVITY THEORY

NASA Astrophysics Data System (ADS)

Zhang, Yi; Gong, Yungui; Zhu, Zong-Hong

2012-04-01

Because of the dynamical equivalence between the f(R) gravity and the Brans-Dicke theory, the dynamical equation in the f(R) gravity is suggested to be derived from a view point of thermodynamics here. By a conformal transformation, the Brans-Dicke theory in the Jordan frame could be expressed as a minimal coupling scalar field theory in Einstein frame. Using the entropy-area relation d˜ {S} = d˜ {A}/4 G, the correct Friedmann equations could be gotten in both frames. Furthermore, we also discuss the corresponding generalized Misner-Sharp energies for theoretical consistence.

Algebraic cycles and local anomalies in F-theory

NASA Astrophysics Data System (ADS)

Bies, Martin; Mayrhofer, Christoph; Weigand, Timo

2017-11-01

We introduce a set of identities in the cohomology ring of elliptic fibrations which are equivalent to the cancellation of gauge and mixed gauge-gravitational anomalies in F-theory compactifications to four and six dimensions. The identities consist in (co)homological relations between complex codimension-two cycles. The same set of relations, once evaluated on elliptic Calabi-Yau three-folds and four-folds, is shown to universally govern the structure of anomalies and their Green-Schwarz cancellation in six- and four-dimensional F-theory vacua, respectively. We furthermore conjecture that these relations hold not only within the cohomology ring, but even at the level of the Chow ring, i.e. as relations among codimension-two cycles modulo rational equivalence. We verify this conjecture in non-trivial examples with Abelian and non-Abelian gauge groups factors. Apart from governing the structure of local anomalies, the identities in the Chow ring relate different types of gauge backgrounds on elliptically fibred Calabi-Yau four-folds.

Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.

PubMed

Midani, Firas S; Weil, Ana A; Chowdhury, Fahima; Begum, Yasmin A; Khan, Ashraful I; Debela, Meti D; Durand, Heather K; Reese, Aspen T; Nimmagadda, Sai N; Silverman, Justin D; Ellis, Crystal N; Ryan, Edward T; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; David, Lawrence A; LaRocque, Regina C

2018-04-12

Cholera is a public health problem worldwide and the risk factors for infection are only partially understood. We prospectively studied household contacts of cholera patients to compare those who were infected with those who were not. We constructed predictive machine learning models of susceptibility using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. We found that machine learning models based on gut microbiota predicted V. cholerae infection as well as models based on known clinical and epidemiological risk factors. A 'predictive gut microbiota' of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.

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

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

Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

PubMed Central

Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.

2016-01-01

Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

Searching for the gut microbial contributing factors to social behavior in rodent models of autism spectrum disorder.

PubMed

Needham, Brittany D; Tang, Weiyi; Wu, Wei-Li

2018-05-01

Social impairment is one of the major symptoms in multiple psychiatric disorders, including autism spectrum disorder (ASD). Accumulated studies indicate a crucial role for the gut microbiota in social development, but these mechanisms remain unclear. This review focuses on two strategies adopted to elucidate the complicated relationship between gut bacteria and host social behavior. In a top-down approach, researchers have attempted to correlate behavioral abnormalities with altered gut microbial profiles in rodent models of ASD, including BTBR mice, maternal immune activation (MIA), maternal valproic acid (VPA) and maternal high-fat diet (MHFD) offspring. In a bottom-up approach, researchers use germ-free (GF) animals, antibiotics, probiotics or pathogens to manipulate the intestinal environment and ascertain effects on social behavior. The combination of both approaches will hopefully pinpoint specific bacterial communities that control host social behavior. Further discussion of how brain development and circuitry is impacted by depletion of gut microbiota is also included. The converging evidence strongly suggests that gut microbes affect host social behavior through the alteration of brain neural circuits. Investigation of intestinal microbiota and host social behavior will unveil any bidirectional communication between the gut and brain and provide alternative therapeutic targets for ASD. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 474-499, 2018. © 2018 Wiley Periodicals, Inc.

Bayesian naturalness, simplicity, and testability applied to the B ‑ L MSSM GUT

NASA Astrophysics Data System (ADS)

Fundira, Panashe; Purves, Austin

2018-04-01

Recent years have seen increased use of Bayesian model comparison to quantify notions such as naturalness, simplicity, and testability, especially in the area of supersymmetric model building. After demonstrating that Bayesian model comparison can resolve a paradox that has been raised in the literature concerning the naturalness of the proton mass, we apply Bayesian model comparison to GUTs, an area to which it has not been applied before. We find that the GUTs are substantially favored over the nonunifying puzzle model. Of the GUTs we consider, the B ‑ L MSSM GUT is the most favored, but the MSSM GUT is almost equally favored.

Rotating charged black hole spacetimes in quadratic f(R) gravitational theories

NASA Astrophysics Data System (ADS)

Nashed, G. G. L.

Motivated by the substantial modifications of gravitational theories and by the models that come out of f(R), we apply the field equation of the charged f(R) = R + βR2 as well as a general vector potential containing three unknown functions to two spherically symmetric spacetimes. We solve the output of the differential equations and derive a class of black holes that are electrically and magnetically rotating spacetimes. The asymptotic behavior of these black holes acts as anti-de Sitter spacetime. Moreover, these solutions have asymptotic curvature singularities as those of General Relativity. We investigate this by calculating the invariants of curvature. Also, we address the issue of the energy conditions and show that the strong energy condition is satisfied provided β > 0. Finally, we compute the conserved quantities like mass and angular momentum.

Tuned and non-Higgsable U(1)s in F-theory

DOE PAGES

Wang, Yi-Nan

2017-03-01

We study the tuning of U(1) gauge fields in F-theory models on a base of general dimension. We construct a formula that computes the change in Weierstrass moduli when such a U(1) is tuned, based on the Morrison-Park form of a Weierstrass model with an additional rational section. Using this formula, we propose the form of “minimal tuning” on any base, which corresponds to the case where the decrease in the number of Weierstrass moduli is minimal. Applying this result, we discover some universal features of bases with non-Higgsable U(1)s. Mathematically, a generic elliptic fibration over such a base hasmore » additional rational sections. Physically, this condition implies the existence of U(1) gauge group in the low-energy supergravity theory after compactification that cannot be Higgsed away. In particular, we show that the elliptic Calabi-Yau manifold over such a base has a small number of complex structure moduli. We also suggest that non-Higgsable U(1)s can never appear on any toric bases. Finally, we construct the first example of a threefold base with non-Higgsable U(1)s.« less

Reconstruction, thermodynamics and stability of the ΛCDM model in f(T,{ T }) gravity

NASA Astrophysics Data System (ADS)

Junior, Ednaldo L. B.; Rodrigues, Manuel E.; Salako, Ines G.; Houndjo, Mahouton J. S.

2016-06-01

We reconstruct the ΛCDM model for f(T,{ T }) theory, where T is the torsion scalar and { T } the trace of the energy-momentum tensor. The result shows that the action of ΛCDM is a combination of a linear term, a constant (-2{{Λ }}) and a nonlinear term given by the product \\sqrt{-T}{F}g[({T}1/3/16π G) (16π G{ T }+T+8{{Λ }})], with F g being a generic function. We show that to maintain conservation of the energy-momentum tensor, we should impose that {F}g[y] must be linear on the trace { T }. This reconstruction decays in f (T) theory for {F}g\\equiv Q, with Q a constant. Our reconstruction describes the cosmological eras to the present time. The model present stability within the geometric and matter perturbations for the choice {F}g=y, where y=({T}1/3/16π G)(16π G{ T }+T+8{{Λ }}), except for the geometric part in the de Sitter model. We impose the first and second laws of thermodynamics to ΛCDM and find the condition where they are satisfied, that is, {T}A,{G}{{eff}}\\gt 0, however where this is not possible in the cases that we choose, this leads to a breakdown of positive entropy and Misner-Sharp energy.

Strong coupling in F-theory and geometrically non-Higgsable seven-branes

NASA Astrophysics Data System (ADS)

Halverson, James

2017-06-01

Geometrically non-Higgsable seven-branes carry gauge sectors that cannot be broken by complex structure deformation, and there is growing evidence that such configurations are typical in F-theory. We study strongly coupled physics associated with these branes. Axiodilaton profiles are computed using Ramanujan's theories of elliptic functions to alternative bases, showing explicitly that the string coupling is O (1) in the vicinity of the brane; that it sources nilpotent SL (2 , Z) monodromy and therefore the associated brane charges are modular; and that essentially all F-theory compactifications have regions with order one string coupling. It is shown that non-perturbative SU (3) and SU (2) seven-branes are related to weakly coupled counterparts with D7-branes via deformation-induced Hanany-Witten moves on (p , q) string junctions that turn them into fundamental open strings; only the former may exist for generic complex structure. D3-brane near these and the Kodaira type II seven-branes probe Argyres-Douglas theories. The BPS states of slightly deformed theories are shown to be dyonic string junctions.

The queen's gut refines with age: longevity phenotypes in a social insect model.

PubMed

Anderson, Kirk E; Ricigliano, Vincent A; Mott, Brendon M; Copeland, Duan C; Floyd, Amy S; Maes, Patrick

2018-06-18

In social insects, identical genotypes can show extreme lifespan variation providing a unique perspective on age-associated microbial succession. In honey bees, short- and long-lived host phenotypes are polarized by a suite of age-associated factors including hormones, nutrition, immune senescence, and oxidative stress. Similar to other model organisms, the aging gut microbiota of short-lived (worker) honey bees accrue Proteobacteria and are depleted of Lactobacillus and Bifidobacterium, consistent with a suite of host senescence markers. In contrast, long-lived (queen) honey bees maintain youthful cellular function with much lower expression of oxidative stress genes, suggesting a very different host environment for age-associated microbial succession. We sequenced the microbiota of 63 honey bee queens exploring two chronological ages and four alimentary tract niches. To control for genetic and environmental variation, we quantified carbonyl accumulation in queen fat body tissue as a proxy for biological aging. We compared our results to the age-specific microbial succession of worker guts. Accounting for queen source variation, two or more bacterial species per niche differed significantly by queen age. Biological aging in queens was correlated with microbiota composition highlighting the relationship of microbiota with oxidative stress. Queens and workers shared many major gut bacterial species, but differ markedly in community structure and age succession. In stark contrast to aging workers, carbonyl accumulation in queens was significantly associated with increased Lactobacillus and Bifidobacterium and depletion of various Proteobacteria. We present a model system linking changes in gut microbiota to diet and longevity, two of the most confounding variables in human microbiota research. The pattern of age-associated succession in the queen microbiota is largely the reverse of that demonstrated for workers. The guts of short-lived worker phenotypes are

An Organismal Model for Gene Regulatory Networks in the Gut-Associated Immune Response

PubMed Central

Buckley, Katherine M.; Rast, Jonathan P.

2017-01-01

The gut epithelium is an ancient site of complex communication between the animal immune system and the microbial world. While elements of self-non-self receptors and effector mechanisms differ greatly among animal phyla, some aspects of recognition, regulation, and response are broadly conserved. A gene regulatory network (GRN) approach provides a means to investigate the nature of this conservation and divergence even as more peripheral functional details remain incompletely understood. The sea urchin embryo is an unparalleled experimental model for detangling the GRNs that govern embryonic development. By applying this theoretical framework to the free swimming, feeding larval stage of the purple sea urchin, it is possible to delineate the conserved regulatory circuitry that regulates the gut-associated immune response. This model provides a morphologically simple system in which to efficiently unravel regulatory connections that are phylogenetically relevant to immunity in vertebrates. Here, we review the organism-wide cellular and transcriptional immune response of the sea urchin larva. A large set of transcription factors and signal systems, including epithelial expression of interleukin 17 (IL17), are important mediators in the activation of the early gut-associated response. Many of these have homologs that are active in vertebrate immunity, while others are ancient in animals but absent in vertebrates or specific to echinoderms. This larval model provides a means to experimentally characterize immune function encoded in the sea urchin genome and the regulatory interconnections that control immune response and resolution across the tissues of the organism. PMID:29109720

Application of dynamical systems theory to the high angle of attack dynamics of the F-14

NASA Technical Reports Server (NTRS)

Jahnke, Craig C.; Culick, Fred E. C.

1990-01-01

Dynamical systems theory has been used to study the nonlinear dynamics of the F-14. An eight degree of freedom model that does not include the control system present in operational F-14s has been analyzed. The aerodynamic model, supplied by NASA, includes nonlinearities as functions of the angles of attack and sideslip, the rotation rate, and the elevator deflection. A continuation method has been used to calculate the steady states of the F-14 as continuous functions of the control surface deflections. Bifurcations of these steady states have been used to predict the onset of wing rock, spiral divergence, and jump phenomena which cause the aircraft to enter a spin. A simple feedback control system was designed to eliminate the wing rock and spiral divergence instabilities. The predictions were verified with numerical simulations.

Diphoton resonance in F-theory inspired flipped $$\\mathrm{SO}(10)$$

DOE PAGES

Leontaris, George K.; Shafi, Qaisar

2016-10-24

Motivated by the di-photon excess at 750 GeV reported by the ATLAS and CMS experiments, we present an F-theory inspired flippedmore » $$\\mathrm{SO}(10)$$ model embedded in ε 6. The low energy spectrum includes the three MSSM chiral families, vector-like colour triplets, several pairs of charged SU(2) L singlet fields (E c,E¯ c), as well as MSSM singlets, one or more of which could contribute to the di-photon resonance. As a result, a total decay width in the multi-GeV range can arise from couplings involving the singlet and MSSM fields.« less

Globally baryon symmetric cosmology, GUT spontaneous symmetry breaking, and the structure of the universe

NASA Technical Reports Server (NTRS)

Stecker, F. W.; Brown, R. W.

1979-01-01

Grand unified theories (GUT) such as SU(5), with spontaneous symmetry breaking, can lead more naturally to a globally baryon symmetric big bang cosmology with a domain structure than to a totally asymmetric cosmology. The symmetry is broken at random in causally independent domains, favoring neither a baryon nor an antibaryon excess on a universal scale. Because of the additional freedom in the high-energy physics allowed by such GUT gauge theories, new observational tests may be possible. Arguments in favor of this cosmology and various observational tests are discussed.

Can a Linear Sigma Model Describe Walking Gauge Theories at Low Energies?

NASA Astrophysics Data System (ADS)

Gasbarro, Andrew

2018-03-01

In recent years, many investigations of confining Yang Mills gauge theories near the edge of the conformal window have been carried out using lattice techniques. These studies have revealed that the spectrum of hadrons in nearly conformal ("walking") gauge theories differs significantly from the QCD spectrum. In particular, a light singlet scalar appears in the spectrum which is nearly degenerate with the PNGBs at the lightest currently accessible quark masses. This state is a viable candidate for a composite Higgs boson. Presently, an acceptable effective field theory (EFT) description of the light states in walking theories has not been established. Such an EFT would be useful for performing chiral extrapolations of lattice data and for serving as a bridge between lattice calculations and phenomenology. It has been shown that the chiral Lagrangian fails to describe the IR dynamics of a theory near the edge of the conformal window. Here we assess a linear sigma model as an alternate EFT description by performing explicit chiral fits to lattice data. In a combined fit to the Goldstone (pion) mass and decay constant, a tree level linear sigma model has a Χ2/d.o.f. = 0.5 compared to Χ2/d.o.f. = 29.6 from fitting nextto-leading order chiral perturbation theory. When the 0++ (σ) mass is included in the fit, Χ2/d.o.f. = 4.9. We remark on future directions for providing better fits to the σ mass.

Metric-affine f (R ,T ) theories of gravity and their applications

NASA Astrophysics Data System (ADS)

Barrientos, E.; Lobo, Francisco S. N.; Mendoza, S.; Olmo, Gonzalo J.; Rubiera-Garcia, D.

2018-05-01

We study f (R ,T ) theories of gravity, where T is the trace of the energy-momentum tensor Tμ ν, with independent metric and affine connection (metric-affine theories). We find that the resulting field equations share a close resemblance with their metric-affine f (R ) relatives once an effective energy-momentum tensor is introduced. As a result, the metric field equations are second-order and no new propagating degrees of freedom arise as compared to GR, which contrasts with the metric formulation of these theories, where a dynamical scalar degree of freedom is present. Analogously to its metric counterpart, the field equations impose the nonconservation of the energy-momentum tensor, which implies nongeodesic motion and consequently leads to the appearance of an extra force. The weak field limit leads to a modified Poisson equation formally identical to that found in Eddington-inspired Born-Infeld gravity. Furthermore, the coupling of these gravity theories to perfect fluids, electromagnetic, and scalar fields, and their potential applications are discussed.

Lack of NLRP3-inflammasome leads to gut-liver axis derangement, gut dysbiosis and a worsened phenotype in a mouse model of NAFLD.

PubMed

Pierantonelli, Irene; Rychlicki, Chiara; Agostinelli, Laura; Giordano, Debora Maria; Gaggini, Melania; Fraumene, Cristina; Saponaro, Chiara; Manghina, Valeria; Sartini, Loris; Mingarelli, Eleonora; Pinto, Claudio; Buzzigoli, Emma; Trozzi, Luciano; Giordano, Antonio; Marzioni, Marco; Minicis, Samuele De; Uzzau, Sergio; Cinti, Saverio; Gastaldelli, Amalia; Svegliati-Baroni, Gianluca

2017-09-22

Non-Alcoholic Fatty Liver Disease (NAFLD) represents the most common form of chronic liver injury and can progress to cirrhosis and hepatocellular carcinoma. A "multi-hit" theory, involving high fat diet and signals from the gut-liver axis, has been hypothesized. The role of the NLRP3-inflammasome, which senses dangerous signals, is controversial. Nlrp3 -/- and wild-type mice were fed a Western-lifestyle diet with fructose in drinking water (HFHC) or a chow diet. Nlrp3 -/- -HFHC showed higher hepatic expression of PPAR γ2 (that regulates lipid uptake and storage) and triglyceride content, histological score of liver injury and greater adipose tissue inflammation. In Nlrp3 -/- -HFHC, dysregulation of gut immune response with impaired antimicrobial peptides expression, increased intestinal permeability and the occurrence of a dysbiotic microbiota led to bacterial translocation, associated with higher hepatic expression of TLR4 (an LPS receptor) and TLR9 (a receptor for double-stranded bacterial DNA). After antibiotic treatment, gram-negative species and bacterial translocation were reduced, and adverse effects restored both in liver and adipose tissue. In conclusion, the combination of a Western-lifestyle diet with innate immune dysfunction leads to NAFLD progression, mediated at least in part by dysbiosis and bacterial translocation, thus identifying new specific targets for NAFLD therapy.

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

A theory for modeling ground-water flow in heterogeneous media

USGS Publications Warehouse

Cooley, Richard L.

2004-01-01

Construction of a ground-water model for a field area is not a straightforward process. Data are virtually never complete or detailed enough to allow substitution into the model equations and direct computation of the results of interest. Formal model calibration through optimization, statistical, and geostatistical methods is being applied to an increasing extent to deal with this problem and provide for quantitative evaluation and uncertainty analysis of the model. However, these approaches are hampered by two pervasive problems: 1) nonlinearity of the solution of the model equations with respect to some of the model (or hydrogeologic) input variables (termed in this report system characteristics) and 2) detailed and generally unknown spatial variability (heterogeneity) of some of the system characteristics such as log hydraulic conductivity, specific storage, recharge and discharge, and boundary conditions. A theory is developed in this report to address these problems. The theory allows construction and analysis of a ground-water model of flow (and, by extension, transport) in heterogeneous media using a small number of lumped or smoothed system characteristics (termed parameters). The theory fully addresses both nonlinearity and heterogeneity in such a way that the parameters are not assumed to be effective values. The ground-water flow system is assumed to be adequately characterized by a set of spatially and temporally distributed discrete values, ?, of the system characteristics. This set contains both small-scale variability that cannot be described in a model and large-scale variability that can. The spatial and temporal variability in ? are accounted for by imagining ? to be generated by a stochastic process wherein ? is normally distributed, although normality is not essential. Because ? has too large a dimension to be estimated using the data normally available, for modeling purposes ? is replaced by a smoothed or lumped approximation y?. (where y is a

Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia.

PubMed

Lim, Joon Seo; Lim, Mi Young; Choi, Yongbin; Ko, GwangPyo

2017-04-20

Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.

Onion thrips, Thrips tabaci, have gut bacteria that are closely related to the symbionts of the western flower thrips, Frankliniella occidentalis.

PubMed

de Vries, Egbert J; van der Wurff, André W G; Jacobs, Gerrit; Breeuwer, Johannes A J

2008-01-01

It has been shown that many insects have Enterobacteriaceae bacteria in their gut system. The western flower thrips, Frankliniella occidentalis Pergande [Thysanoptera: Thripidae], has a symbiotic relation with Erwinia species gut bacteria. To determine if other Thripidae species have similar bacterial symbionts, the onion thrips, Thrips tabaci, was studied because, like F. occidentalis, it is phytophagous. Contrary to F. occidentalis, T. tabaci is endemic in Europe and biotypes have been described. Bacteria were isolated from the majority of populations and biotypes of T. tabaci examined. Bacteria were present in high numbers in most individuals of the populations studied. Like F. occidentalis, T. tabaci contained one type of bacterium that clearly outnumbered all other types present in the gut. This bacterium was identified as an Erwinia species, as was also the case for F. occidentalis. However, its biochemical characteristics and 16S rDNA sequence differed from the bacteria present in F. occidentalis.

Onion Thrips, Thrips tabaci, Have Gut Bacteria That are Closely Related to the Symbionts of the Western Flower Thrips, Frankliniella occidentalis

PubMed Central

de Vries, Egbert J.; van der Wurff, André W. G.; Jacobs, Gerrit; Breeuwer, Johannes A. J.

2008-01-01

It has been shown that many insects have Enterobacteriaceae bacteria in their gut system. The western flower thrips, Frankliniella occidentalis Pergande [Thysanoptera: Thripidae], has a symbiotic relation with Erwinia species gut bacteria. To determine if other Thripidae species have similar bacterial symbionts, the onion thrips, Thrips tabaci, was studied because, like F. occidentalis, it is phytophagous. Contrary to F. occidentalis, T. tabaci is endemic in Europe and biotypes have been described. Bacteria were isolated from the majority of populations and biotypes of T. tabaci examined. Bacteria were present in high numbers in most individuals of the populations studied. Like F. occidentalis, T. tabaci contained one type of bacterium that clearly outnumbered all other types present in the gut. This bacterium was identified as an Erwinia species, as was also the case for F. occidentalis. However, its biochemical characteristics and 16S rDNA sequence differed from the bacteria present in F. occidentalis. PMID:20298113

Model-independent limits and constraints on extended theories of gravity from cosmic reconstruction techniques

NASA Astrophysics Data System (ADS)

de la Cruz-Dombriz, Álvaro; Dunsby, Peter K. S.; Luongo, Orlando; Reverberi, Lorenzo

2016-12-01

The onset of dark energy domination depends on the particular gravitational theory driving the cosmic evolution. Model independent techniques are crucial to test the both the present ΛCDM cosmological paradigm and alternative theories, making the least possible number of assumptions about the Universe. In this paper we investigate whether cosmography is able to distinguish between different gravitational theories, by determining bounds on model parameters for three different extensions of General Relativity, namely quintessence, F(𝒯) and f(R) gravitational theories. We expand each class of theories in powers of redshift z around the present time, making no additional assumptions. This procedure is an extension of previous work and can be seen as the most general approach for testing extended theories of gravity through the use of cosmography. In the case of F(𝒯) and f(R) theories, we show that some assumptions on model parameters often made in previous works are superfluous or even unjustified. We use data from the Union 2.1 supernovae catalogue, baryonic acoustic oscillation data and H(z) differential age compilations, which probe cosmology on different scales of the cosmological evolution. We perform a Monte Carlo analysis using a Metropolis-Hastings algorithm with a Gelman-Rubin convergence criterion, reporting 1-σ and 2-σ confidence levels. To do so, we perform two distinct fits, assuming only data within z < 1 first and then without limitations in redshift. We obtain the corresponding numerical intervals in which coefficients span, and find that the data is compatible the ΛCDM limit of all three theories at the 1-σ level, while still compatible with quite a large portion of parameter space. We compare our results to the truncated ΛCDM paradigm, demonstrating that our bounds divert from the expectations of previous works, showing that the permitted regions of coefficients are significantly modified and in general widened with respect to

Model-independent limits and constraints on extended theories of gravity from cosmic reconstruction techniques

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

Cruz-Dombriz, Álvaro de la; Dunsby, Peter K.S.; Luongo, Orlando

The onset of dark energy domination depends on the particular gravitational theory driving the cosmic evolution. Model independent techniques are crucial to test the both the present ΛCDM cosmological paradigm and alternative theories, making the least possible number of assumptions about the Universe. In this paper we investigate whether cosmography is able to distinguish between different gravitational theories, by determining bounds on model parameters for three different extensions of General Relativity, namely quintessence, F (Τ) and f ( R ) gravitational theories. We expand each class of theories in powers of redshift z around the present time, making no additionalmore » assumptions. This procedure is an extension of previous work and can be seen as the most general approach for testing extended theories of gravity through the use of cosmography. In the case of F (Τ) and f ( R ) theories, we show that some assumptions on model parameters often made in previous works are superfluous or even unjustified. We use data from the Union 2.1 supernovae catalogue, baryonic acoustic oscillation data and H ( z ) differential age compilations, which probe cosmology on different scales of the cosmological evolution. We perform a Monte Carlo analysis using a Metropolis-Hastings algorithm with a Gelman-Rubin convergence criterion, reporting 1-σ and 2-σ confidence levels. To do so, we perform two distinct fits, assuming only data within z < 1 first and then without limitations in redshift. We obtain the corresponding numerical intervals in which coefficients span, and find that the data is compatible the ΛCDM limit of all three theories at the 1-σ level, while still compatible with quite a large portion of parameter space. We compare our results to the truncated ΛCDM paradigm, demonstrating that our bounds divert from the expectations of previous works, showing that the permitted regions of coefficients are significantly modified and in general widened with respect

Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis.

PubMed

Song, Han; Yoo, Young; Hwang, Junghyun; Na, Yun-Cheol; Kim, Heenam Stanley

2016-03-01

Atopic dermatitis (AD) is a serious global epidemic associated with a modern lifestyle. Although aberrant interactions between gut microbes and the intestinal immune system have been implicated in this skin disease, the nature of the microbiome dysfunction underlying the disease remains unclear. The gut microbiome from 132 subjects, including 90 patients with AD, was analyzed by using 16S rRNA gene and metagenome sequence analyses. Reference genomes from the Human Microbiome Project and the KEGG Orthology database were used for metagenome analyses. Short-chain fatty acids in fecal samples were compared by using gas chromatographic-mass spectrometric analyses. We show that enrichment of a subspecies of the major gut species Faecalibacterium prausnitzii is strongly associated with AD. In addition, the AD microbiome was enriched in genes encoding the use of various nutrients that could be released from damaged gut epithelium, reflecting a bloom of auxotrophic bacteria. Fecal samples from patients with AD showed decreased levels of butyrate and propionate, which have anti-inflammatory effects. This is likely a consequence of an intraspecies compositional change in F prausnitzii that reduces the number of high butyrate and propionate producers, including those related to the strain A2-165, a lack of which has been implicated in patients with Crohn disease. The data suggest that feedback interactions between dysbiosis in F prausnitzii and dysregulation of gut epithelial inflammation might underlie the chronic progression of AD by resulting in impairment of the gut epithelial barrier, which ultimately leads to aberrant TH2-type immune responses to allergens in the skin. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[A machine learning model using gut microbiome data for predicting changes of trimethylamine-N-oxide in healthy volunteers after choline consumption].

PubMed

Lu, Jun-Qi; Wang, Shan; Yin, Jia; Wu, Shan; He, Yan; Zheng, Hui-Min; Sheng, Hua-Fang; Zhou, Hong-Wei

2017-03-20

To establish a machine learning model based on gut microbiota for predicting the level of trimethylamine N-oxide (TMAO) metabolism in vivo after choline intake to provide guidance of individualized precision diet and evidence for screening population at high risks of cardiovascular disease. We quantified plasma levels of TMAO in 18 healthy volunteers before and 8 h after a choline challenge (ingestion of two boiled eggs). The volunteers were divided into two groups with increased or decreased TMAO level following choline challenge. Fresh fecal samples were collected before taking fasting blood samples for amplifying 16S rRNA V4 tags, and the PCR products were sequenced using the platform of Illumina HiSeq 2000. The differences in gut microbiata between subjects with increased and decreased plasma TMAO were analyzed using QIIME. Based on the gut microbiota data and TMAO levels in the two groups, the prediction model was established using the machine learning random forest algorithm, and the validity of the model was tested using a verified dataset. An obvious difference was found in beta diversity of the gut microbota between the subjects with increased and decreased plasma TMAO level following choline challenge. The area under the curve (AUC) of the model was 86.39% (95% CI: 72.7%-100%). Using the verified dataset, the model showed a much higher probability for correctly predicting TMAO variation following choline challenge. The model is feasible and reliable for predicting the level of TMAO metabolism in vivo based on gut microbiota.

Dual little strings from F-theory and flop transitions

NASA Astrophysics Data System (ADS)

Hohenegger, Stefan; Iqbal, Amer; Rey, Soo-Jong

2017-07-01

A particular two-parameter class of little string theories can be described by M parallel M5-branes probing a transverse affine A N - 1 singularity. We previously discussed the duality between the theories labelled by ( N, M) and ( M, N). In this work, we propose that these two are in fact only part of a larger web of dual theories. We provide evidence that the theories labelled by ( N, M) and (NM/k,k) are dual to each other, where k = gcd( N, M). To argue for this duality, we use a geometric realization of these little string theories in terms of F-theory compactifications on toric, non-compact Calabi-Yau threefolds X N, M which have a double elliptic fibration structure. We show explicitly for a number of examples that X NM/ k, k is part of the extended moduli space of X N, M , i.e. the two are related through symmetry transformations and flop transitions. By working out the full duality map, we provide a simple check at the level of the free energy of little string theories.

Modeling wormholes in f (R ,T ) gravity

NASA Astrophysics Data System (ADS)

Moraes, P. H. R. S.; Sahoo, P. K.

2017-08-01

In this work, we propose the modeling of static wormholes within the f (R ,T ) extended theory of gravity perspective. We present some models of wormholes, which are constructed from different hypotheses for their matter content, i.e., different relations for their pressure components (radial and lateral) and different equations of state. The solutions obtained for the shape function of the wormholes obey the necessary metric conditions. They show a behavior similar to those found in previous references about wormholes, which also happens to our solutions for the energy density of such objects. We also apply the energy conditions for the wormholes' physical content.

New integrable models and analytical solutions in f (R ) cosmology with an ideal gas

NASA Astrophysics Data System (ADS)

Papagiannopoulos, G.; Basilakos, Spyros; Barrow, John D.; Paliathanasis, Andronikos

2018-01-01

In the context of f (R ) gravity with a spatially flat FLRW metric containing an ideal fluid, we use the method of invariant transformations to specify families of models which are integrable. We find three families of f (R ) theories for which new analytical solutions are given and closed-form solutions are provided.

[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.

Halo modelling in chameleon theories

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

Lombriser, Lucas; Koyama, Kazuya; Li, Baojiu, E-mail: lucas.lombriser@port.ac.uk, E-mail: kazuya.koyama@port.ac.uk, E-mail: baojiu.li@durham.ac.uk

2014-03-01

We analyse modelling techniques for the large-scale structure formed in scalar-tensor theories of constant Brans-Dicke parameter which match the concordance model background expansion history and produce a chameleon suppression of the gravitational modification in high-density regions. Thereby, we use a mass and environment dependent chameleon spherical collapse model, the Sheth-Tormen halo mass function and linear halo bias, the Navarro-Frenk-White halo density profile, and the halo model. Furthermore, using the spherical collapse model, we extrapolate a chameleon mass-concentration scaling relation from a ΛCDM prescription calibrated to N-body simulations. We also provide constraints on the model parameters to ensure viability on localmore » scales. We test our description of the halo mass function and nonlinear matter power spectrum against the respective observables extracted from large-volume and high-resolution N-body simulations in the limiting case of f(R) gravity, corresponding to a vanishing Brans-Dicke parameter. We find good agreement between the two; the halo model provides a good qualitative description of the shape of the relative enhancement of the f(R) matter power spectrum with respect to ΛCDM caused by the extra attractive gravitational force but fails to recover the correct amplitude. Introducing an effective linear power spectrum in the computation of the two-halo term to account for an underestimation of the chameleon suppression at intermediate scales in our approach, we accurately reproduce the measurements from the N-body simulations.« less

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.

A 3-dimensional mathematical model of microbial proliferation that generates the characteristic cumulative relative abundance distributions in gut microbiomes

PubMed Central

Takayasu, Lena; Suda, Wataru; Watanabe, Eiichiro; Fukuda, Shinji; Takanashi, Kageyasu; Ohno, Hiroshi; Takayasu, Misako; Takayasu, Hideki; Hattori, Masahira

2017-01-01

The gut microbiome is highly variable among individuals, largely due to differences in host lifestyle and physiology. However, little is known about the underlying processes or rules that shape the complex microbial community. In this paper, we show that the cumulative relative abundance distribution (CRAD) of microbial species can be approximated by a power law function, and found that the power exponent of CRADs generated from 16S rRNA gene and metagenomic data for normal gut microbiomes of humans and mice was similar consistently with ∼0.9. A similarly robust power exponent was observed in CRADs of gut microbiomes during dietary interventions and several diseases. However, the power exponent was found to be ∼0.6 in CRADs from gut microbiomes characterized by lower species richness, such as those of human infants and the small intestine of mice. In addition, the CRAD of gut microbiomes of mice treated with antibiotics differed slightly from those of infants and the small intestines of mice. Based on these observations, in addition to data on the spatial distribution of microbes in the digestive tract, we developed a 3-dimensional mathematical model of microbial proliferation that reproduced the experimentally observed CRAD patterns. Our model indicated that the CRAD may be determined by the ratio of emerging to pre-existing species during non-uniform spatially competitive proliferation, independent of species composition. PMID:28792501

Bianchi Type-II String Cosmological Model with Magnetic Field in f ( R, T) Gravity

NASA Astrophysics Data System (ADS)

Sharma, N. K.; Singh, J. K.

2014-09-01

The spatially homogeneous and totally anisotropic Bianchi type-II cosmological solutions of massive strings have been investigated in the presence of the magnetic field in the framework of f( R, T) gravity proposed by Harko et al. (Phys Rev D 84:024020, 2011). With the help of special law of variation for Hubble's parameter proposed by Berman (Nuovo Cimento B 74:182, 1983) cosmological model is obtained in this theory. We consider f( R, T) model and investigate the modification R+ f( T) in Bianchi type-II cosmology with an appropriate choice of a function f( T)= μ T. We use the power law relation between average Hubble parameter H and average scale factor R to find the solution. The assumption of constant deceleration parameter leads to two models of universe, i.e. power law model and exponential model. Some physical and kinematical properties of the model are also discussed.

Engineering the gut microbiota to treat hyperammonemia.

PubMed

Shen, Ting-Chin David; Albenberg, Lindsey; Bittinger, Kyle; Chehoud, Christel; Chen, Ying-Yu; Judge, Colleen A; Chau, Lillian; Ni, Josephine; Sheng, Michael; Lin, Andrew; Wilkins, Benjamin J; Buza, Elizabeth L; Lewis, James D; Daikhin, Yevgeny; Nissim, Ilana; Yudkoff, Marc; Bushman, Frederic D; Wu, Gary D

2015-07-01

Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.

E(lementary)-strings in six-dimensional heterotic F-theory

NASA Astrophysics Data System (ADS)

Choi, Kang-Sin; Rey, Soo-Jong

2017-09-01

Using E-strings, we can analyze not only six-dimensional superconformal field theories but also probe vacua of non-perturabative heterotic string. We study strings made of D3-branes wrapped on various two-cycles in the global F-theory setup. We claim that E-strings are elementary in the sense that various combinations of E-strings can form M-strings as well as heterotic strings and new kind of strings, called G-strings. Using them, we show that emissions and combinations of heterotic small instantons generate most of known six-dimensional superconformal theories, their affinizations and little string theories. Taking account of global structure of compact internal geometry, we also show that special combinations of E-strings play an important role in constructing six-dimensional theories of D- and E-types. We check global consistency conditions from anomaly cancellation conditions, both from five-branes and strings, and show that they are given in terms of elementary E-string combinations.

Oral Administration of a Select Mixture of Bacillus Probiotics Affects the Gut Microbiota and Goblet Cell Function following Escherichia coli Challenge in Newly Weaned Pigs of Genotype MUC4 That Are Supposed To Be Enterotoxigenic E. coli F4ab/ac Receptor Negative.

PubMed

Zhang, Wei; Zhu, Yao-Hong; Zhou, Dong; Wu, Qiong; Song, Dan; Dicksved, Johan; Wang, Jiu-Feng

2017-02-01

Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. Low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to piglets of genotype MUC4 that are supposed to be F4-expressing enterotoxigenic Escherichia coli strain (F4 + ETEC) F4ab/ac receptor negative (i.e., MUC4-resistant piglets) for 1 week before F4 + ETEC challenge. The luminal contents were collected from the mucosa of the colon on day 8 after F4 + ETEC challenge. The BLS mix attenuated E. coli-induced expansion of Bacteroides uniformis, Eubacterium eligens, Acetanaerobacterium, and Sporobacter populations. Clostridium and Turicibacter populations increased following F4 + ETEC challenge in pigs pretreated with low-dose BLS mix. Lactobacillus gasseri and Lactobacillus salivarius populations increased after administration of BLS mix during E. coli infection. The beneficial effects of BLS mix were due in part to the expansion of certain Clostridium, Lactobacillus, and Turicibacter populations, with a corresponding increase in the number of goblet cells in the ileum via upregulated Atoh1 expression, in turn increasing MUC2 production and thus preserving the mucus barrier and enhancing host defenses against enteropathogenic bacteria. However, excessive BLS mix consumption may increase the risk for enteritis, partly through disruption of colonic microbial ecology, characterized by expansion of Proteobacteria and impaired goblet cell function in the ileum. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. The present study is important for improving our understanding of the protective role of probiotics against Escherichia coli infection in piglets. Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. In this

Oral Administration of a Select Mixture of Bacillus Probiotics Affects the Gut Microbiota and Goblet Cell Function following Escherichia coli Challenge in Newly Weaned Pigs of Genotype MUC4 That Are Supposed To Be Enterotoxigenic E. coli F4ab/ac Receptor Negative

PubMed Central

Zhang, Wei; Zhou, Dong; Wu, Qiong; Song, Dan; Dicksved, Johan; Wang, Jiu-Feng

2016-01-01

ABSTRACT Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. Low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to piglets of genotype MUC4 that are supposed to be F4-expressing enterotoxigenic Escherichia coli strain (F4+ ETEC) F4ab/ac receptor negative (i.e., MUC4-resistant piglets) for 1 week before F4+ ETEC challenge. The luminal contents were collected from the mucosa of the colon on day 8 after F4+ ETEC challenge. The BLS mix attenuated E. coli-induced expansion of Bacteroides uniformis, Eubacterium eligens, Acetanaerobacterium, and Sporobacter populations. Clostridium and Turicibacter populations increased following F4+ ETEC challenge in pigs pretreated with low-dose BLS mix. Lactobacillus gasseri and Lactobacillus salivarius populations increased after administration of BLS mix during E. coli infection. The beneficial effects of BLS mix were due in part to the expansion of certain Clostridium, Lactobacillus, and Turicibacter populations, with a corresponding increase in the number of goblet cells in the ileum via upregulated Atoh1 expression, in turn increasing MUC2 production and thus preserving the mucus barrier and enhancing host defenses against enteropathogenic bacteria. However, excessive BLS mix consumption may increase the risk for enteritis, partly through disruption of colonic microbial ecology, characterized by expansion of Proteobacteria and impaired goblet cell function in the ileum. Our findings suggest that oral administration of BLS mix reprograms the gut microbiota and enhances goblet cell function to ameliorate enteritis. IMPORTANCE The present study is important for improving our understanding of the protective role of probiotics against Escherichia coli infection in piglets. Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric

Emergence of running dark energy from polynomial f( R) theory in Palatini formalism

NASA Astrophysics Data System (ADS)

Szydłowski, Marek; Stachowski, Aleksander; Borowiec, Andrzej

2017-09-01

We consider FRW cosmology in f(R)= R+ γ R^2+δ R^3 modified framework. The Palatini approach reduces its dynamics to the simple generalization of Friedmann equation. Thus we study the dynamics in two-dimensional phase space with some details. After reformulation of the model in the Einstein frame, it reduces to the FRW cosmological model with a homogeneous scalar field and vanishing kinetic energy term. This potential determines the running cosmological constant term as a function of the Ricci scalar. As a result we obtain the emergent dark energy parametrization from the covariant theory. We study also singularities of the model and demonstrate that in the Einstein frame some undesirable singularities disappear.

Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships.

PubMed

Lyte, Mark; Fodor, Anthony A; Chapman, Clinton D; Martin, Gary G; Perez-Chanona, Ernesto; Jobin, Christian; Dess, Nancy K

2016-06-01

The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress. Occidental low and high-saccharin-consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition. The saccharin phenotype was confirmed (low-saccharin-consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin-consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate. The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.

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.

f(R) theories of gravity with coupling between matter and geometry in autonomous system

NASA Astrophysics Data System (ADS)

Wang, Jun; Gui, Ruoyu; Qiu, Wenjun

2018-03-01

In this paper, a general approach has been introduced to investigate f(R) theories of gravity with coupling between matter and geometry via autonomous system, where there is no need to specify the arbitrary function of the scalar curvature. By this way, we find the general condition for the cosmic accelerated expansion. Moreover, in order to exemplify how to use our method to study specific cases, we applied it to three different models.

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.

Distorting general relativity: gravity's rainbow and f(R) theories at work

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

Garattini, Remo, E-mail: Remo.Garattini@unibg.it

2013-06-01

We compute the Zero Point Energy in a spherically symmetric background combining the high energy distortion of Gravity's Rainbow with the modification induced by a f(R) theory. Here f(R) is a generic analytic function of the Ricci curvature scalar R in 4D and in 3D. The explicit calculation is performed for a Schwarzschild metric. Due to the spherically symmetric property of the Schwarzschild metric we can compare the effects of the modification induced by a f(R) theory in 4D and in 3D. We find that the final effect of the combined theory is to have finite quantities that shift themore » Zero Point Energy. In this context we setup a Sturm-Liouville problem with the cosmological constant considered as the associated eigenvalue. The eigenvalue equation is a reformulation of the Wheeler-DeWitt equation which is analyzed by means of a variational approach based on gaussian trial functionals. With the help of a canonical decomposition, we find that the relevant contribution to one loop is given by the graviton quantum fluctuations around the given background. A final discussion on the connection of our result with the observed cosmological constant is also reported.« less

Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models

PubMed Central

Hwang, In Young; Koh, Elvin; Wong, Adison; March, John C.; Bentley, William E.; Lee, Yung Seng; Chang, Matthew Wook

2017-01-01

Bacteria can be genetically engineered to kill specific pathogens or inhibit their virulence. We previously developed a synthetic genetic system that allows a laboratory strain of Escherichia coli to sense and kill Pseudomonas aeruginosa in vitro. Here, we generate a modified version of the system, including a gene encoding an anti-biofilm enzyme, and use the probiotic strain Escherichia coli Nissle 1917 as host. The engineered probiotic shows in vivo prophylactic and therapeutic activity against P. aeruginosa during gut infection in two animal models (Caenorhabditis elegans and mice). These findings support the further development of engineered microorganisms with potential prophylactic and therapeutic activities against gut infections. PMID:28398304

Impact of dietary deviation on disease progression and gut microbiome composition in lupus-prone SNF1 mice

PubMed Central

Johnson, B M; Gaudreau, M-C; Al-Gadban, M M; Gudi, R; Vasu, C

2015-01-01

Environmental factors, including microbes and diet, play a key role in initiating autoimmunity in genetically predisposed individuals. However, the influence of gut microflora in the initiation and progression of systemic lupus erythematosus (SLE) is not well understood. In this study, we have examined the impact of drinking water pH on immune response, disease incidence and gut microbiome in a spontaneous mouse model of SLE. Our results show that (SWR × NZB) F1 (SNF1) mice that were given acidic pH water (AW) developed nephritis at a slower pace compared to those on neutral pH water (NW). Immunological analyses revealed that the NW-recipient mice carry relatively higher levels of circulating autoantibodies against nuclear antigen (nAg) as well as plasma cells. Importantly, 16S rRNA gene-targeted sequencing revealed that the composition of gut microbiome is significantly different between NW and AW groups of mice. In addition, analysis of cytokine and transcription factor expression revealed that immune response in the gut mucosa of NW recipient mice is dominated by T helper type 17 (Th17) and Th9-associated factors. Segmented filamentous bacteria (SFB) promote a Th17 response and autoimmunity in mouse models of arthritis and multiple sclerosis. Interestingly, however, not only was SFB colonization unaffected by the pH of drinking water, but also SFB failed to cause a profound increase in Th17 response and had no significant effect on lupus incidence. Overall, these observations show that simple dietary deviations such as the pH of drinking water can influence lupus incidence and affect the composition of gut microbiome. PMID:25703185

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

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.

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.

Gut microbiota in experimental murine model of Graves' orbitopathy established in different environments may modulate clinical presentation of disease.

PubMed

Masetti, Giulia; Moshkelgosha, Sajad; Köhling, Hedda-Luise; Covelli, Danila; Banga, Jasvinder Paul; Berchner-Pfannschmidt, Utta; Horstmann, Mareike; Diaz-Cano, Salvador; Goertz, Gina-Eva; Plummer, Sue; Eckstein, Anja; Ludgate, Marian; Biscarini, Filippo; Marchesi, Julian Roberto

2018-05-25

Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves' disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves' orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO. We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the

On Analytical Solutions of f(R) Modified Gravity Theories in FLRW Cosmologies

NASA Astrophysics Data System (ADS)

Domazet, Silvije; Radovanović, Voja; Simonović, Marko; Štefančić, Hrvoje

2013-02-01

A novel analytical method for f(R) modified theories without matter in Friedmann-Lemaitre-Robertson-Walker (FLRW) spacetimes is introduced. The equation of motion for the scale factor in terms of cosmic time is reduced to the equation for the evolution of the Ricci scalar R with the Hubble parameter H. The solution of equation of motion for actions of the form of power law in Ricci scalar R is presented with a detailed elaboration of the action quadratic in R. The reverse use of the introduced method is exemplified in finding functional forms f(R), which leads to specified scale factor functions. The analytical solutions are corroborated by numerical calculations with excellent agreement. Possible further applications to the phases of inflationary expansion and late-time acceleration as well as f(R) theories with radiation are outlined.

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.

BPS states in N = 2 supersymmetric G2 and F4 models

NASA Astrophysics Data System (ADS)

Ahl Laamara, R.; Mellal, O.; Saidi, E. H.

2017-07-01

In BPS quiver theory of N = 2 supersymmetric pure gauge models with gauge invariance G, primitive BPS quivers Q0G are of two types: Q0ADE and Q0BCFG. In this study, we first show that Q0ADE have outer-automorphism symmetries inherited from the outer-automorphisms of the Dynkin diagrams of ADE Lie algebras. Then, we extend the usual folding operation of Dynkin diagrams ADE → BCFG to obtain the two following things: (i) relate Q0BCFG quivers and their mutations to the Q0ADE ones and their mutations; and (ii) link the BPS chambers of the N = 2ADE theories with the corresponding BCFG ones. As an illustration of this construction, we derive the BPS and anti-BPS states of the strong chambers QstgG2 and QstgF4 of the 4d N = 2 pure G2 and F4 gauge models.

General U(1)×U(1) F-theory compactifications and beyond: geometry of unHiggsings and novel matter structure

DOE PAGES

Cvetic, Mirjam; Klevers, Denis; Piragua, Hernan; ...

2015-11-30

We construct the general form of an F-theory compactification with two U(1) factors based on a general elliptically fibered Calabi-Yau manifold with Mordell-Weil group of rank two. This construction produces broad classes of models with diverse matter spectra, including many that are not realized in earlier F-theory constructions with U(1)×U(1) gauge symmetry. Generic U(1)×U(1) models can be related to a Higgsed non-Abelian model with gauge group SU(2)×SU(2)×SU(3), SU(2) 3×SU(3), or a subgroup thereof. The nonlocal horizontal divisors of the Mordell-Weil group are replaced with local vertical divisors associated with the Cartan generators of non-Abelian gauge groups from Kodaira singularities. Wemore » give a global resolution of codimension two singularities of the Abelian model; we identify the full anomaly free matter content, and match it to the unHiggsed non-Abelian model. The non-Abelian Weierstrass model exhibits a new algebraic description of the singularities in the fibration that results in the first explicit construction of matter in the symmetric representation of SU(3). This matter is realized on double point singularities of the discriminant locus. In conclusion, the construction suggests a generalization to U(1) k factors with k > 2, which can be studied by Higgsing theories with larger non-Abelian gauge groups.« less

The influence of Staphylococcus aureus on gut microbial ecology in an in vitro continuous culture human colonic model system.

PubMed

Sannasiddappa, Thippeswamy H; Costabile, Adele; Gibson, Glenn R; Clarke, Simon R

2011-01-01

An anaerobic three-stage continuous culture model of the human colon (gut model), which represent different anatomical areas of the large intestine, was used to study the effect of S. aureus infection of the gut on the resident faecal microbiota. Studies on the development of the microbiota in the three vessels were performed and bacteria identified by culture independent fluorescence in situ hybridization (FISH). Furthermore, short chain fatty acids (SCFA), as principal end products of gut bacterial metabolism, were measured along with a quantitative assessment of the predominant microbiota. During steady state conditions, numbers of S. aureus cells stabilised until they were washed out, but populations of indigenous bacteria were transiently altered; thus S. aureus was able to compromise colonisation resistance by the colonic microbiota. Furthermore, the concentration of butyric acid in the vessel representing the proximal colon was significantly decreased by infection. Thus infection by S. aureus appears to be able to alter the overall structure of the human colonic microbiota and the microbial metabolic profiles. This work provides an initial in vitro model to analyse interactions with pathogens.

Functional analysis of C1 family cysteine peptidases in the larval gut of Тenebrio molitor and Tribolium castaneum.

PubMed

Martynov, Alexander G; Elpidina, Elena N; Perkin, Lindsey; Oppert, Brenda

2015-02-14

Larvae of the tenebrionids Tenebrio molitor and Tribolium castaneum have highly compartmentalized guts, with primarily cysteine peptidases in the acidic anterior midgut that contribute to the early stages of protein digestion. High throughput sequencing was used to quantify and characterize transcripts encoding cysteine peptidases from the C1 papain family in the gut of tenebrionid larvae. For T. castaneum, 25 genes and one questionable pseudogene encoding cysteine peptidases were identified, including 11 cathepsin L or L-like, 11 cathepsin B or B-like, and one each F, K, and O. The majority of transcript expression was from two cathepsin L genes on chromosome 10 (LOC659441 and LOC659502). For cathepsin B, the major expression was from genes on chromosome 3 (LOC663145 and LOC663117). Some transcripts were expressed at lower levels or not at all in the larval gut, including cathepsins F, K, and O. For T. molitor, there were 29 predicted cysteine peptidase genes, including 14 cathepsin L or L-like, 13 cathepsin B or B-like, and one each cathepsin O and F. One cathepsin L and one cathepsin B were also highly expressed, orthologous to those in T. castaneum. Peptidases lacking conservation in active site residues were identified in both insects, and sequence analysis of orthologs indicated that changes in these residues occurred prior to evolutionary divergence. Sequences from both insects have a high degree of variability in the substrate binding regions, consistent with the ability of these enzymes to degrade a variety of cereal seed storage proteins and inhibitors. Predicted cathepsin B peptidases from both insects included some with a shortened occluding loop without active site residues in the middle, apparently lacking exopeptidase activity and unique to tenebrionid insects. Docking of specific substrates with models of T. molitor cysteine peptidases indicated that some insect cathepsins B and L bind substrates with affinities similar to human cathepsin L, while

An Evolutionary Game Theory Model of Spontaneous Brain Functioning.

PubMed

Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro; Mocenni, Chiara; Santarnecchi, Emiliano

2017-11-22

Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.

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.

Transcytosis of F4 fimbriae by villous and dome epithelia in F4-receptor positive pigs supports importance of receptor-dependent endocytosis in oral immunization strategies.

PubMed

Snoeck, Veerle; Van den Broeck, Wim; De Colvenaer, Veerle; Verdonck, Frank; Goddeeris, Bruno; Cox, Eric

2008-07-15

Very few antigens have been described that induce an intestinal immunity when given orally. Our laboratory demonstrated that oral administration of isolated F4 (K88) fimbriae of Escherichia coli to F4-receptor positive (F4R(+)) pigs induces protective mucosal immunity against challenge infection. However, presence of F4-receptors (F4R) on villous enterocytes is a prerequisite for inducing the immune response, as no F4-specific antibody-secreting cells (ASC) can be induced in F4R(-) pigs. In this study, the in vivo binding of isolated F4 fimbriae (F4) to the gut epithelium was examined in F4R(+) and F4R(-) pigs. It was further investigated whether binding of F4 to the F4R results in endocytosis in and translocation across the gut epithelium using microscopy. F4 did not adhere to the intestinal epithelium of F4R(-) pigs, whereas it strongly adhered to the villous epithelium and the follicle-associated epithelium (FAE) of the jejunum and ileum of F4R(+) pigs. Following binding to F4R, F4 was endocytosed by villous enterocytes, follicle-associated enterocytes and M cells. Transcytosis of F4 across the epithelium resulted in the appearance of F4 in the lamina propria and dome region of the jejunal and ileal PP. This is the first study showing transcytosis of fimbriae across the gut epithelium. This receptor-dependent transcytosis can explain the success of F4 fimbriae as oral immunogen for inducing protective immunity in F4R(+) pigs strengthening the importance of receptor-dependent endocytosis and translocation in oral vaccine strategies. Further identification of the receptor responsible for this transport is in progress.

Gut microbiota-bone axis.

PubMed

Villa, Christopher R; Ward, Wendy E; Comelli, Elena M

2017-05-24

The gut microbiota (GM) is an important regulator of body homeostasis, including intestinal and extra-intestinal effects. This review focuses on the GM-bone axis, which we define as the effect of the gut-associated microbial community or the molecules they synthesize, on bone health. While research in this field is limited, findings from preclinical studies support that gut microbes positively impact bone mineral density and strength parameters. Moreover, administration of beneficial bacteria (probiotics) in preclinical models has demonstrated higher bone mineralization and greater bone strength. The preferential bacterial genus that has shown these beneficial effects in bone is Lactobacillus and thus lactobacilli are among the best candidates for future clinical intervention trials. However, their effectiveness is dependent on stage of development, as early life constitutes an important time for impacting bone health, perhaps via modulation of the GM. In addition, sex-specific difference also impacts the efficacy of the probiotics. Although auspicious, many questions regarding the GM-bone axis require consideration of potential mechanisms; sex-specific efficacy; effective dose of probiotics; and timing and duration of treatment.

Frozen up dilaton and the GUT/Planck mass ratio

NASA Astrophysics Data System (ADS)

Davidson, Aharon; Ygael, Tomer

2017-09-01

By treating modulus and phase on equal footing, as prescribed by Dirac, local scale invariance can consistently accompany any Brans-Dicke ω-theory. We show that in the presence of a soft scale symmetry breaking term, the classical solution, if it exists, cannot be anything else but general relativistic. The dilaton modulus gets frozen up by the Weyl-Proca vector field, thereby constituting a gravitational quasi-Higgs mechanism. Assigning all grand unified scalars as dilatons, they enjoy Weyl universality, and upon symmetry breaking, the Planck (mass)2 becomes the sum of all their individual (VEV)2s. The emerging GUT/Planck (mass)2 ratio is thus ∼ ωgGUT2 / 4 π.

Constraining f (R ) Gravity Theory Using Weak Lensing Peak Statistics from the Canada-France-Hawii-Telescope Lensing Survey

NASA Astrophysics Data System (ADS)

Liu, Xiangkun; Li, Baojiu; Zhao, Gong-Bo; Chiu, Mu-Chen; Fang, Wei; Pan, Chuzhong; Wang, Qiao; Du, Wei; Yuan, Shuo; Fu, Liping; Fan, Zuhui

2016-07-01

In this Letter, we report the observational constraints on the Hu-Sawicki f (R ) theory derived from weak lensing peak abundances, which are closely related to the mass function of massive halos. In comparison with studies using optical or x-ray clusters of galaxies, weak lensing peak analyses have the advantages of not relying on mass-baryonic observable calibrations. With observations from the Canada-France-Hawaii-Telescope Lensing Survey, our peak analyses give rise to a tight constraint on the model parameter |fR 0| for n =1 . The 95% C.L. is log10|fR 0|<-4.82 given WMAP9 priors on (Ωm , As ). With Planck15 priors, the corresponding result is log10|fR 0|<-5.16 .

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...

Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model.

PubMed

Collins, K H; Paul, H A; Reimer, R A; Seerattan, R A; Hart, D A; Herzog, W

2015-11-01

Osteoarthritis (OA) may result from intrinsic inflammation related to metabolic disturbance. Obesity-associated inflammation is triggered by lipopolysaccharide (LPS) derived from the gut microbiota. However, the relationship between gut microbiota, LPS, inflammation, and OA remain unclear. To evaluate the associations between gut microbiota, systemic LPS levels, serum and local inflammatory profiles, and joint damage in a high fat/high sucrose diet induced obese rat model. 32 rats were randomized to a high fat/high sucrose diet (diet-induced obese (DIO), 40% fat, 45% sucrose, n = 21) or chow diet group (12% fat, 3.7% sucrose n = 11) for 28 weeks. After a 12-week obesity induction period, DIO animals were stratified into Obesity Prone (DIO-P, top 33% by change in body mass, n = 7), and Obesity Resistant groups (DIO-R, bottom 33%, n = 7). At sacrifice, joints were scored using a Modified Mankin Criteria. Blood and synovial fluid analytes, serum LPS, and fecal gut microbiota were analyzed. DIO animals had greater Modified Mankin scores than chow animals (P = 0.002). There was a significant relationship (r = 0.604, p = 0.001) between body fat, but not body mass, and Modified Mankin score. Eighteen synovial fluid and four serum analytes were increased in DIO animals. DIO serum LPS levels were increased compared to chow (P = 0.031). Together, Lactobacillus species (spp.) and Methanobrevibacter spp. abundance had a strong predictive relationship with Modified Mankin Score (r(2) = 0.5, P < 0.001). Increased OA in DIO animals is associated with greater body fat, not body mass. The link between gut microbiota and adiposity-derived inflammation and metabolic OA warrants further investigation. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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

Viability of Noether Symmetry of F( R) Theory of Gravity

NASA Astrophysics Data System (ADS)

Sarkar, Kaushik; Sk, Nayem; Debnath, Subhra; Sanyal, Abhik Kumar

2013-04-01

Recently, we have explored vices and virtues of R^{3/2} term in the action which has in-built Noether symmetry and anticipated that a linear term might improve the situation (Sarkar et al., arXiv:1201.2987 [astro-ph.CO], 2012). In the absence of a conserved current it is extremely difficult to obtain an analytical solution of the said fourth order theory of gravity in the presence of a linear term. Here, we therefore enlarge the configuration space by including a scalar field in addition and also taking some of the anisotropic models (in the absence of a scalar field) into account. We observe that Noether symmetry remains obscure and it does not even reproduce the one that already exists in the literature (Sanyal, Gen. Relativ. Gravit., 37:407, 2005). However, there exists in general, a conserved current for F( R) theory of gravity in the presence of a non-minimally coupled scalar field (Sanyal, Phys. Lett. B, 624:81, 2005; Mod. Phys. Lett. A, 25:2667, 2010), which simplifies the field equations considerably. Here, we briefly expatiate the non-Noether conserved current and show that indeed the situation is modified.

Challenges of metabolomics in human gut microbiota research.

PubMed

Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

2016-08-01

The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

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.

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.

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.

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 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.

Maternal high fat diet and its consequence on the gut microbiome: A rat model.

PubMed

Mann, Phyllis E; Huynh, Kevin; Widmer, Giovanni

2017-11-14

The biological changes that occur during pregnancy in the female mammal include shifts in hormonal regulation in preparation for parturition and lactation, and changes in energy metabolism. In women, studies have also shown that during pregnancy there is a reduction in bacterial species richness in the gut. In the current experiment rats were used to model the interaction of diet, reproductive status, and intestinal bacterial microbiota during pregnancy and lactation. In Experiment 1 rats were exposed to either standard chow or high-fat chow (60%) and were divided into two groups: unmated (NULL) or mated (RE). In Experiment 2, both NULL and RE rats were exposed to high-fat chow for a 30-day period. High-throughput sequencing of the 16S rRNA gene revealed that pregnancy impacted the gut microbiota in a similar manner to humans. The impact of reproductive status on microbiota composition, however, was stronger in rats fed a high-fat (HF) diet. Diet-induced changes replicated some of the changes observed in humans, such as increasing the Firmicutes/Bacteroidetes ratio. However, in contrast to humans, pregnancy in rats did not increase β-diversity between microbiota from different animals. These results indicate that during pregnancy in rats, the gut microbiota is altered in a similar manner to that which occurs in women, and that these changes are further exaggerated by exposure to a HF diet. Thus, the rat may allow modelling the effects of consumption of HF food during pregnancy and enable future studies to determine the risks of HF diets during pregnancy and its consequences on the offspring.

Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease.

PubMed

Caputi, Valentina; Giron, Maria Cecilia

2018-06-06

Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut⁻brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the

Mean-field theory for multipole ordering in f-electron systems on the basis of a j-j coupling scheme

NASA Astrophysics Data System (ADS)

Yamamura, Ryosuke; Hotta, Takashi

2018-05-01

We develop a microscopic theory for multipole ordering, applicable to the system with plural numbers of f electrons per ion, from an itinerant picture on the basis of a j-j coupling scheme. For the purpose, by introducing the Γ8 Hubbard Hamiltonian as the minimum model to discuss the multipole ordering in f-electron systems, we describe the mean-field approximation in terms of the multipole operators. For the case of n = 2 , where n denotes the average f-electron number per ion, we analyze the model on a simple cubic lattice to obtain the multipole phase diagram. In particular, we find the order of non-Kramers Γ3 quadrupoles, O20 and O22 , with different ordering vectors. We attempt to explain the phase diagram from the discussion on the interaction energy.

Modulation of Active Gut Microbiota by Lactobacillus rhamnosus GG in a Diet Induced Obesity Murine Model.

PubMed

Ji, Yosep; Park, Soyoung; Park, Haryung; Hwang, Eunchong; Shin, Hyeunkil; Pot, Bruno; Holzapfel, Wilhelm H

2018-01-01

Gut microbiota play a key role in the development of metabolic disorders. Defining and correlating structural shifts in gut microbial assemblages with conditions related to metabolic syndrome have, however, been proven difficult. Results from 16S genomic DNA and 16S ribosomal RNA analyses of fecal samples may differ widely, leading to controversial information on the whole microbial community and metabolically active microbiota. Using a C57BL/6J murine model, we compared data from 16S genomic DNA and ribosomal RNA of the fecal microbiota. The study included three groups of experimental animals comprising two groups with high fat diet induced obesity (DIO) while a third group (control) received a low fat diet. One of the DIO groups was treated with the probiotic Lactobacillus rhamnosus GG (LGG). Compared to the data obtained by DNA analysis, a significantly higher abundance of OTUs was accounted for by RNA analysis. Moreover, rRNA based analysis showed a modulation of the active gut microbial population in the DIO group receiving LGG, thus reflecting a change in the induced obesity status of the host. As one of the most widely studied probiotics the functionality of LGG has been linked to the alleviation of metabolic syndrome, and, in some cases, to an impact on the microbiome. Yet, it appears that no study has reported thus far on modulation of the active microbiota by LGG treatment. It is postulated that the resulting impact on calorie consumption affects weight gain concomitantly with modulation of the functional structure of the gut microbial population. Using the 16S rRNA based approach therefore decisively increased the precision of gut microbiota metagenome analysis.

Validating hyperbilirubinemia and gut mucosal atrophy with a novel ultramobile ambulatory total parenteral nutrition piglet model

USDA-ARS?s Scientific Manuscript database

Total parenteral nutrition (TPN) provides all nutrition intravenously. Although TPN therapy has grown enormously, it causes significant complications, including gut and hepatic dysfunction. Current models use animal tethering which is unlike ambulatory human TPN delivery and is cost prohibitive. We ...

Strange stars in f( R) theories of gravity in the Palatini formalism

NASA Astrophysics Data System (ADS)

Panotopoulos, Grigoris

2017-05-01

In the present work we study strange stars in f( R) theories of gravity in the Palatini formalism. We consider two concrete well-known cases, namely the R+R^2/(6 M^2) model as well as the R-μ ^4/R model for two different values of the mass parameter M or μ . We integrate the modified Tolman-Oppenheimer-Volkoff equations numerically, and we show the mass-radius diagram for each model separately. The standard case corresponding to the General Relativity is also shown in the same figure for comparison. Our numerical results show that the interior solution can be vastly different depending on the model and/or the value of the parameter of each model. In addition, our findings imply that (i) for the cosmologically interesting values of the mass scales M,μ the effect of modified gravity on strange stars is negligible, while (ii) for the values predicting an observable effect, the modified gravity models discussed here would be ruled out by their cosmological effects.

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

CONSTRUCTION OF EDUCATIONAL THEORY MODELS.

ERIC Educational Resources Information Center

MACCIA, ELIZABETH S.; AND OTHERS

THIS STUDY DELINEATED MODELS WHICH HAVE POTENTIAL USE IN GENERATING EDUCATIONAL THEORY. A THEORY MODELS METHOD WAS FORMULATED. BY SELECTING AND ORDERING CONCEPTS FROM OTHER DISCIPLINES, THE INVESTIGATORS FORMULATED SEVEN THEORY MODELS. THE FINAL STEP OF DEVISING EDUCATIONAL THEORY FROM THE THEORY MODELS WAS PERFORMED ONLY TO THE EXTENT REQUIRED TO…

Comparison of planktonic and biofilm-associated communities of Clostridium difficile and indigenous gut microbiota in a triple-stage chemostat gut model.

PubMed

Crowther, Grace S; Chilton, Caroline H; Todhunter, Sharie L; Nicholson, Scott; Freeman, Jane; Baines, Simon D; Wilcox, Mark H

2014-08-01

Biofilms are characteristic of some chronic or recurrent infections and this mode of growth tends to reduce treatment efficacy. Clostridium difficile infection (CDI) is associated with a high rate of recurrent symptomatic disease. The presence and behaviour of C. difficile within intestinal biofilms remains largely unexplored, but may factor in recurrent infection. A triple-stage chemostat gut model designed to facilitate the formation of intestinal biofilm was inoculated with a pooled human faecal emulsion. Bacterial populations were allowed to equilibrate before simulated CDI was induced by clindamycin (33.9 mg/L, four times daily, 7 days) and subsequently treated with vancomycin (125 mg/L, four times daily, 7 days). Indigenous gut microbiota, C. difficile total viable counts, spores, cytotoxin and antimicrobial activity in planktonic and biofilm communities were monitored during the 10 week experimental period. Vancomycin successfully treated the initial episode of simulated CDI, but ∼18 days after therapy cessation, recurrent infection occurred. Germination, proliferation and toxin production were evident within planktonic communities in both initial and recurrent CDI. In contrast, sessile C. difficile remained in dormant spore form for the duration of the experiment. The effects of and recovery from clindamycin and vancomycin exposure for sessile populations was delayed compared with responses for planktonic bacteria. Intestinal biofilms provide a potential reservoir for C. difficile spore persistence, possibly facilitating their dispersal into the gut lumen after therapeutic intervention, leading to recurrent infection. Therapeutic options for CDI could have increased efficacy if they are more effective against sessile C. difficile. © 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.

Quantitative prediction of shrimp disease incidence via the profiles of gut eukaryotic microbiota.

PubMed

Xiong, Jinbo; Yu, Weina; Dai, Wenfang; Zhang, Jinjie; Qiu, Qiongfen; Ou, Changrong

2018-04-01

One common notion is emerging that gut eukaryotes are commensal or beneficial, rather than detrimental. To date, however, surprisingly few studies have been taken to discern the factors that govern the assembly of gut eukaryotes, despite growing interest in the dysbiosis of gut microbiota-disease relationship. Herein, we firstly explored how the gut eukaryotic microbiotas were assembled over shrimp postlarval to adult stages and a disease progression. The gut eukaryotic communities changed markedly as healthy shrimp aged, and converged toward an adult-microbiota configuration. However, the adult-like stability was distorted by disease exacerbation. A null model untangled that the deterministic processes that governed the gut eukaryotic assembly tended to be more important over healthy shrimp development, whereas this trend was inverted as the disease progressed. After ruling out the baseline of gut eukaryotes over shrimp ages, we identified disease-discriminatory taxa (species level afforded the highest accuracy of prediction) that characteristic of shrimp health status. The profiles of these taxa contributed an overall 92.4% accuracy in predicting shrimp health status. Notably, this model can accurately diagnose the onset of shrimp disease. Interspecies interaction analysis depicted how the disease-discriminatory taxa interacted with one another in sustaining shrimp health. Taken together, our findings offer novel insights into the underlying ecological processes that govern the assembly of gut eukaryotes over shrimp postlarval to adult stages and a disease progression. Intriguingly, the established model can quantitatively and accurately predict the incidences of shrimp disease.

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.

Hypersurface Homogeneous Cosmological Model in Modified Theory of Gravitation

NASA Astrophysics Data System (ADS)

Katore, S. D.; Hatkar, S. P.; Baxi, R. J.

2016-12-01

We study a hypersurface homogeneous space-time in the framework of the f (R, T) theory of gravitation in the presence of a perfect fluid. Exact solutions of field equations are obtained for exponential and power law volumetric expansions. We also solve the field equations by assuming the proportionality relation between the shear scalar (σ ) and the expansion scalar (θ ). It is observed that in the exponential model, the universe approaches isotropy at large time (late universe). The investigated model is notably accelerating and expanding. The physical and geometrical properties of the investigated model are also discussed.

F(R) cosmology via Noether symmetry and Λ-Chaplygin Gas like model

NASA Astrophysics Data System (ADS)

Fazlollahi, H. R.

2018-06-01

In this work, we consider f (R) alternative theories of gravity with an eye to Noether symmetry through the gauge theorem. For non-vacuum models, one finds Λ like gravity with energy density of Chaplygin Gas. We also obtain the effective equation of state parameter for corresponding cosmology and scale factor behavior with respect to cosmic time which show that the model provides viable EoS and scale factor with respect to observational data.

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.

Quantum equivalence of f (R) gravity and scalar-tensor theories in the Jordan and Einstein frames

NASA Astrophysics Data System (ADS)

Ohta, Nobuyoshi

2018-03-01

The f(R) gravity and scalar-tensor theory are known to be equivalent at the classical level. We study if this equivalence is valid at the quantum level. There are two descriptions of the scalar-tensor theory in the Jordan and Einstein frames. It is shown that these three formulations of the theories give the same determinant or effective action on shell, and thus they are equivalent at the quantum one-loop level on shell in arbitrary dimensions. We also compute the one-loop divergence in f(R) gravity on an Einstein space.

The roles of 4f- and 5f-orbitals in bonding: A magnetochemical, crystal field, density functional theory, and multi-reference wavefunction study

DOE PAGES

Lukens, Wayne W.; Speldrich, Manfred; Yang, Ping; ...

2016-05-31

The electronic structures of 4f 3/5f 3 Cp" 3M and Cp" 3M·alkylisocyanide complexes, where Cp" is 1,3-bis-(trimethylsilyl)cyclopentadienyl, are explored with a focus on the splitting of the f-orbitals, which provides information about the strengths of the metal–ligand interactions. While the f-orbital splitting in many lanthanide complexes has been reported in detail, experimental determination of the f-orbital splitting in actinide complexes remains rare in systems other than halide and oxide compounds, since the experimental approach, crystal field analysis, is generally significantly more difficult for actinide complexes than for lanthanide complexes. In this study, a set of analogous neodymium(III) and uranium(III) tris-cyclopentadienylmore » complexes and their isocyanide adducts was characterized by electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility. The crystal field model was parameterized by combined fitting of EPR and susceptibility data, yielding an accurate description of f-orbital splitting. The isocyanide derivatives were also studied using density functional theory, resulting in f-orbital splitting that is consistent with crystal field fitting, and by multi-reference wavefunction calculations that support the electronic structure analysis derived from the crystal-field calculations. The results highlight that the 5f-orbitals, but not the 4f-orbitals, are significantly involved in bonding to the isocyanide ligands. The main interaction between isocyanide ligand and the metal center is a σ-bond, with additional 5f to π* donation for the uranium complexes. As a result, while interaction with the isocyanide π*-orbitals lowers the energies of the 5f xz2 and 5f yz2-orbitals, spin–orbit coupling greatly reduces the population of 5f xz2 and 5f yz2 in the ground state.« less

Therapeutic modulation of gut microbiota: current clinical applications and future perspectives.

PubMed

Ianiro, Gianluca; Bibbò, Stefano; Gasbarrini, Antonio; Cammarota, Giovanni

2014-01-01

Human beings and gut microbiota are in a symbiotic relationship, and the hypothesis of a "super organism" composed of the human organism and microbes has been recently proposed. The gut microbiota fulfills important metabolic and immunological tasks, and the impairment of its composition might alter homeostasis and lead to the development of microbiota-related diseases. The most common illnesses associated with alterations of the gut microbiota include inflammatory bowel disease, gastroenteric infections, irritable bowel syndrome and other gastrointestinal functional diseases, colorectal cancer, metabolic syndrome and obesity, liver diseases, allergic diseases, and neurological diseases such as autism. In theory, every disease associated with the impairment of intestinal microflora might benefit from the therapeutic modulation of the gut microbiota. A number of attempts to manipulate the microbiota have not produced identical results for every disease. Although antibiotics and probiotics have been available for a long time, the so-called fecal microbiota transplantation, which is a very old remedy, was only recently re-evaluated as a promising therapeutic approach for microbiota impairment. A comprehensive understanding of the gut microbiota composition, in states of both health and various diseases, is needed for the development of future approaches for microbiota modulation and for developing targeted therapies. In this review, we describe the role of the microbiota in several diseases and the related treatment options that are currently available.

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.

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...

Investigation of the Fe{sup 3+} centers in perovskite KMgF{sub 3} through a combination of ab initio (density functional theory) and semi-empirical (superposition model) calculations

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

Emül, Y.; Department of Software Engineering, Cumhuriyet University, 58140 Sivas; Erbahar, D.

2015-08-14

Analyses of the local crystal and electronic structure in the vicinity of Fe{sup 3+} centers in perovskite KMgF{sub 3} crystal have been carried out in a comprehensive manner. A combination of density functional theory (DFT) and a semi-empirical superposition model (SPM) is used for a complete analysis of all Fe{sup 3+} centers in this study for the first time. Some quantitative information has been derived from the DFT calculations on both the electronic structure and the local geometry around Fe{sup 3+} centers. All of the trigonal (K-vacancy case, K-Li substitution case, and normal trigonal Fe{sup 3+} center case), FeF{sub 5}Omore » cluster, and tetragonal (Mg-vacancy and Mg-Li substitution cases) centers have been taken into account based on the previously suggested experimental and theoretical inferences. The collaboration between the experimental data and the results of both DFT and SPM calculations provides us to understand most probable structural model for Fe{sup 3+} centers in KMgF{sub 3}.« less

Inheritance and Establishment of Gut Microbiota in Chickens

PubMed Central

Ding, Jinmei; Dai, Ronghua; Yang, Lingyu; He, Chuan; Xu, Ke; Liu, Shuyun; Zhao, Wenjing; Xiao, Lu; Luo, Lingxiao; Zhang, Yan; Meng, He

2017-01-01

In mammals, the microbiota can be transmitted from the placenta, uterus, and vagina of the mother to the infant. Unlike mammals, development of the avian embryo is a process isolated from the mother and thus in the avian embryo the gut microbial developmental process remains elusive. To explore the establishment and inheritance of the gut microbiome in the avian embryo, we used the chicken as the model organism to investigate the gut microbial composition in embryos, chicks, and maternal hens. We observed: (1) 28 phyla and 162 genera of microbes in embryos where the dominated genus was Halomonas (79%). (2) 65 genera were core microbiota in all stages with 42% and 62% gut microbial genera of embryo were found in maternal hen and chick, respectively. There was a moderate correlation (0.40) between the embryo and maternal, and 0.52 between the embryo and chick at the family level. (3) Gut microbes that are involved in substance metabolism, infectious disease, and environmental adaptation are enriched in embryos, chicks, and maternal hens, respectively. (4) 94% genera of gut microbial composition were similar among three different chicken breeds which were maintained under similar conditions. Our findings provide evidence to support the hypothesis that part of the microbial colonizers harbored in early embryos were inherited from maternal hens, and the gut microbial abundance and diversity were influenced by environmental factors and host genetic variation during development. PMID:29067020

Evidence for a core gut microbiota in the zebrafish

PubMed Central

Roeselers, Guus; Mittge, Erika K; Stephens, W Zac; Parichy, David M; Cavanaugh, Colleen M; Guillemin, Karen; Rawls, John F

2011-01-01

Experimental analysis of gut microbial communities and their interactions with vertebrate hosts is conducted predominantly in domesticated animals that have been maintained in laboratory facilities for many generations. These animal models are useful for studying coevolved relationships between host and microbiota only if the microbial communities that occur in animals in lab facilities are representative of those that occur in nature. We performed 16S rRNA gene sequence-based comparisons of gut bacterial communities in zebrafish collected recently from their natural habitat and those reared for generations in lab facilities in different geographic locations. Patterns of gut microbiota structure in domesticated zebrafish varied across different lab facilities in correlation with historical connections between those facilities. However, gut microbiota membership in domesticated and recently caught zebrafish was strikingly similar, with a shared core gut microbiota. The zebrafish intestinal habitat therefore selects for specific bacterial taxa despite radical differences in host provenance and domestication status. PMID:21472014

F4 symmetric ϕ3 theory at four loops

NASA Astrophysics Data System (ADS)

Gracey, J. A.

2017-03-01

The renormalization group functions for six dimensional scalar ϕ3 theory with an F4 symmetry are provided at four loops in the modified minimal subtraction (MS ¯ ) scheme. Aside from the anomalous dimension of ϕ and the β -function this includes the mass operator and a ϕ2-type operator. The anomalous dimension of the latter is computed explicitly at four loops for the 26 and 324 representations of F4. The ɛ expansion of all the related critical exponents are determined to O (ɛ4). For instance the value for Δϕ agrees with recent conformal bootstrap estimates in 5 and 5.95 dimensions. The renormalization group functions are also provided at four loops for the group E6.

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

The obese gut microbiome across the epidemiologic transition.

PubMed

Dugas, Lara R; Fuller, Miles; Gilbert, Jack; Layden, Brian T

2016-01-01

The obesity epidemic has emerged over the past few decades and is thought to be a result of both genetic and environmental factors. A newly identified factor, the gut microbiota, which is a bacterial ecosystem residing within the gastrointestinal tract of humans, has now been implicated in the obesity epidemic. Importantly, this bacterial community is impacted by external environmental factors through a variety of undefined mechanisms. We focus this review on how the external environment may impact the gut microbiota by considering, the host's geographic location 'human geography', and behavioral factors (diet and physical activity). Moreover, we explore the relationship between the gut microbiota and obesity with these external factors. And finally, we highlight here how an epidemiologic model can be utilized to elucidate causal relationships between the gut microbiota and external environment independently and collectively, and how this will help further define this important new factor in the obesity epidemic.

Community assembly of the worm gut microbiome

NASA Astrophysics Data System (ADS)

Gore, Jeff

It has become increasingly clear that human health is strongly influenced by the bacteria that live within the gut, known collectively as the gut microbiome. This complex community varies tremendously between individuals, but understanding the sources that lead to this heterogeneity is challenging. To address this challenge, we are using a bottom-up approach to develop a predictive understanding of how the microbiome assembles and functions within a simple and experimentally tractable gut, the gut of the worm C. elegans. We have found that stochastic community assembly in the C. elegansintestine is sufficient to produce strong inter-worm heterogeneity in community composition. When worms are fed with two neutrally-competing fluorescently labeled bacterial strains, we observe stochastically-driven bimodality in community composition, where approximately half of the worms are dominated by each bacterial strain. A simple model incorporating stochastic colonization suggests that heterogeneity between worms is driven by the low rate at which bacteria successfully establish new intestinal colonies. We can increase this rate experimentally by feeding worms at high bacterial density; in these conditions the bimodality disappears. We have also characterized all pairwise interspecies competitions among a set of eleven bacterial species, illuminating the rules governing interspecies community assembly. These results demonstrate the potential importance of stochastic processes in bacterial community formation and suggest a role for C. elegans as a model system for ecology of host-associated communities.

Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism.

PubMed

Zhang, Limin; Xie, Cen; Nichols, Robert G; Chan, Siu H J; Jiang, Changtao; Hao, Ruixin; Smith, Philip B; Cai, Jingwei; Simons, Margaret N; Hatzakis, Emmanuel; Maranas, Costas D; Gonzalez, Frank J; Patterson, Andrew D

2016-01-01

The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism. Predictions about the metabolic contribution of the gut microbiota to the host were made using 16S rRNA-based PICRUSt ( p hylogenetic i nvestigation of c ommunities by r econstruction of u nobserved st ates), then validated using 1 H nuclear magnetic resonance-based metabolomics, and results were summarized by using genome-scale metabolic models. Oral Gly-MCA administration altered the gut microbial community structure, notably reducing the ratio of Firmicutes to Bacteroidetes and its PICRUSt-predicted metabolic function, including reduced production of short-chain fatty acids (substrates for hepatic gluconeogenesis and de novo lipogenesis) in the ceca of HFD-fed mice. Metabolic improvement was intestinal FXR dependent, as revealed by the lack of changes in HFD-fed intestine-specific Fxr -null ( Fxr ΔIE ) mice treated with Gly-MCA. Integrative analyses based on genome-scale metabolic models demonstrated an important link between Lactobacillus and Clostridia bile salt hydrolase activity and bacterial fermentation. Hepatic metabolite levels after Gly-MCA treatment correlated with altered levels of gut bacterial species. In conclusion, modulation of the gut microbiota by inhibition of intestinal FXR signaling alters host liver lipid metabolism and improves obesity-related metabolic dysfunction. IMPORTANCE The farnesoid X receptor (FXR) plays an important role in mediating the dialog between the host

Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism

PubMed Central

Zhang, Limin; Xie, Cen; Nichols, Robert G.; Chan, Siu H. J.; Jiang, Changtao; Hao, Ruixin; Smith, Philip B.; Cai, Jingwei; Simons, Margaret N.; Hatzakis, Emmanuel; Maranas, Costas D.; Gonzalez, Frank J.

2016-01-01

ABSTRACT The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism. Predictions about the metabolic contribution of the gut microbiota to the host were made using 16S rRNA-based PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), then validated using 1H nuclear magnetic resonance-based metabolomics, and results were summarized by using genome-scale metabolic models. Oral Gly-MCA administration altered the gut microbial community structure, notably reducing the ratio of Firmicutes to Bacteroidetes and its PICRUSt-predicted metabolic function, including reduced production of short-chain fatty acids (substrates for hepatic gluconeogenesis and de novo lipogenesis) in the ceca of HFD-fed mice. Metabolic improvement was intestinal FXR dependent, as revealed by the lack of changes in HFD-fed intestine-specific Fxr-null (FxrΔIE) mice treated with Gly-MCA. Integrative analyses based on genome-scale metabolic models demonstrated an important link between Lactobacillus and Clostridia bile salt hydrolase activity and bacterial fermentation. Hepatic metabolite levels after Gly-MCA treatment correlated with altered levels of gut bacterial species. In conclusion, modulation of the gut microbiota by inhibition of intestinal FXR signaling alters host liver lipid metabolism and improves obesity-related metabolic dysfunction. IMPORTANCE The farnesoid X receptor (FXR) plays an important role in mediating the dialog between the host

The need for an intermediate mass scale in GUTs

NASA Technical Reports Server (NTRS)

Shafi, Q.

1983-01-01

The minimal SU(5) grand unified field theory (GUT) model fails to resolve the strong charge parity (CP) problem, suffers from the cosmological monopole problem, sheds no light on the nature of the 'dark' mass in the universe, and predicts an unacceptably low value for the baryon asymmetry. All these problems can be overcome in suitable grand unified axion models with an intermediate mass scale of about 10 to the 11th power to 10 to the 12th power GeV. An example based on the gauge group SO(10) is presented. Among other things, it predicts that the axions comprise the 'dark' mass in the universe, and that there exists a galactic monopole flux of 10 to the -8th power to 10 to the -7th power/sq cm/yr. Other topics that are briefly discussed include proton decay, family symmetry, neutrino masses and the gauge hierarchy problem.

Gut Microbiota in a Rat Oral Sensitization Model: Effect of a Cocoa-Enriched Diet.

PubMed

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

2017-01-01

Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota. Lewis rats were orally sensitized and fed with either a standard or 10% cocoa diet. Faecal microbiota was analysed through metagenomics study. Intestinal IgA concentration was also determined. Oral sensitization produced few changes in intestinal microbiota, but in those rats fed a cocoa diet significant modifications appeared. Decreased bacteria from the Firmicutes and Proteobacteria phyla and a higher percentage of bacteria belonging to the Tenericutes and Cyanobacteria phyla were observed. In conclusion, a cocoa diet is able to modify the microbiota bacterial pattern in orally sensitized animals. As cocoa inhibits the synthesis of specific antibodies and also intestinal IgA, those changes in microbiota pattern, particularly those of the Proteobacteria phylum, might be partially responsible for the tolerogenic effect of cocoa.

Barrierless association of CF2 and dissociation of C2F4 by variational transition-state theory and system-specific quantum Rice–Ramsperger–Kassel theory

PubMed Central

Bao, Junwei Lucas; Zhang, Xin

2016-01-01

Bond dissociation is a fundamental chemical reaction, and the first principles modeling of the kinetics of dissociation reactions with a monotonically increasing potential energy along the dissociation coordinate presents a challenge not only for modern electronic structure methods but also for kinetics theory. In this work, we use multifaceted variable-reaction-coordinate variational transition-state theory (VRC-VTST) to compute the high-pressure limit dissociation rate constant of tetrafluoroethylene (C2F4), in which the potential energies are computed by direct dynamics with the M08-HX exchange correlation functional. To treat the pressure dependence of the unimolecular rate constants, we use the recently developed system-specific quantum Rice–Ramsperger–Kassel theory. The calculations are carried out by direct dynamics using an exchange correlation functional validated against calculations that go beyond coupled-cluster theory with single, double, and triple excitations. Our computed dissociation rate constants agree well with the recent experimental measurements. PMID:27834727

Barrierless association of CF2 and dissociation of C2F4 by variational transition-state theory and system-specific quantum Rice-Ramsperger-Kassel theory.

PubMed

Bao, Junwei Lucas; Zhang, Xin; Truhlar, Donald G

2016-11-29

Bond dissociation is a fundamental chemical reaction, and the first principles modeling of the kinetics of dissociation reactions with a monotonically increasing potential energy along the dissociation coordinate presents a challenge not only for modern electronic structure methods but also for kinetics theory. In this work, we use multifaceted variable-reaction-coordinate variational transition-state theory (VRC-VTST) to compute the high-pressure limit dissociation rate constant of tetrafluoroethylene (C 2 F 4 ), in which the potential energies are computed by direct dynamics with the M08-HX exchange correlation functional. To treat the pressure dependence of the unimolecular rate constants, we use the recently developed system-specific quantum Rice-Ramsperger-Kassel theory. The calculations are carried out by direct dynamics using an exchange correlation functional validated against calculations that go beyond coupled-cluster theory with single, double, and triple excitations. Our computed dissociation rate constants agree well with the recent experimental measurements.

Density functional theory of electron transfer beyond the Born-Oppenheimer approximation: Case study of LiF

NASA Astrophysics Data System (ADS)

Li, Chen; Requist, Ryan; Gross, E. K. U.

2018-02-01

We perform model calculations for a stretched LiF molecule, demonstrating that nonadiabatic charge transfer effects can be accurately and seamlessly described within a density functional framework. In alkali halides like LiF, there is an abrupt change in the ground state electronic distribution due to an electron transfer at a critical bond length R = Rc, where an avoided crossing of the lowest adiabatic potential energy surfaces calls the validity of the Born-Oppenheimer approximation into doubt. Modeling the R-dependent electronic structure of LiF within a two-site Hubbard model, we find that nonadiabatic electron-nuclear coupling produces a sizable elongation of the critical Rc by 0.5 bohr. This effect is very accurately captured by a simple and rigorously derived correction, with an M-1 prefactor, to the exchange-correlation potential in density functional theory, M = reduced nuclear mass. Since this nonadiabatic term depends on gradients of the nuclear wave function and conditional electronic density, ∇Rχ(R) and ∇Rn(r, R), it couples the Kohn-Sham equations at neighboring R points. Motivated by an observed localization of nonadiabatic effects in nuclear configuration space, we propose a local conditional density approximation—an approximation that reduces the search for nonadiabatic density functionals to the search for a single function y(n).

Gut microbiota and the development of obesity.

PubMed

Boroni Moreira, A P; Fiche Salles Teixeira, T; do C Gouveia Peluzio, M; de Cássia Gonçalves Alfenas, R

2012-01-01

Advances in tools for molecular investigations have allowed deeper understanding of how microbes can influence host physiology. A very interesting field of research that has gained attention recently is the possible role of gut microbiota in the development of obesity and metabolic disorders. The aim of this review is to discuss mechanisms that explain the influence of gut microbiota on host metabolism. The gut microbiota is important for normal physiology of the host. However, differences in their composition may have different impacts on host metabolism. It has been shown that obese and lean subjects present different microbiota composition profile. These differences in microbiota composition may contribute to weight imbalance and impaired metabolism. The evidences from animal models suggest that it is possible that the microbiota of obese subjects has higher capacity to harvest energy from the diet providing substrates that can activate lipogenic pathways. In addition, microorganisms can also influence the activity of lipoprotein lipase interfering in the accumulation of triglycerides in the adipose tissue. The interaction of gut microbiota with the endocannabinoid system provides a route through which intestinal permeability can be altered. Increased intestinal permeability allows the entrance of endotoxins to the circulation, which are related to the induction of inflammation and insulin resistance in mice. The impact of the proposed mechanisms for humans still needs further investigations. However, the fact that gut microbiota can be modulated through dietary components highlights the importance to study how fatty acids, carbohydrates, micronutrients, prebiotics, and probiotics can influence gut microbiota composition and the management of obesity. Gut microbiota seems to be an important and promising target in the prevention and treatment of obesity and its related metabolic disturbances in future studies and in clinical practice.

Links between Dietary Protein Sources, the Gut Microbiota, and Obesity.

PubMed

Madsen, Lise; Myrmel, Lene S; Fjære, Even; Liaset, Bjørn; Kristiansen, Karsten

2017-01-01

The association between the gut microbiota and obesity is well documented in both humans and in animal models. It is also demonstrated that dietary factors can change the gut microbiota composition and obesity development. However, knowledge of how diet, metabolism and gut microbiota mutually interact and modulate energy metabolism and obesity development is still limited. Epidemiological studies indicate an association between intake of certain dietary protein sources and obesity. Animal studies confirm that different protein sources vary in their ability to either prevent or induce obesity. Different sources of protein such as beans, vegetables, dairy, seafood, and meat differ in amino acid composition. Further, the type and level of other factors, such as fatty acids and persistent organic pollutants (POPs) vary between dietary protein sources. All these factors can modulate the composition of the gut microbiota and may thereby influence their obesogenic properties. This review summarizes evidence of how different protein sources affect energy efficiency, obesity development, and the gut microbiota, linking protein-dependent changes in the gut microbiota with obesity.

Links between Dietary Protein Sources, the Gut Microbiota, and Obesity

PubMed Central

Madsen, Lise; Myrmel, Lene S.; Fjære, Even; Liaset, Bjørn; Kristiansen, Karsten

2017-01-01

The association between the gut microbiota and obesity is well documented in both humans and in animal models. It is also demonstrated that dietary factors can change the gut microbiota composition and obesity development. However, knowledge of how diet, metabolism and gut microbiota mutually interact and modulate energy metabolism and obesity development is still limited. Epidemiological studies indicate an association between intake of certain dietary protein sources and obesity. Animal studies confirm that different protein sources vary in their ability to either prevent or induce obesity. Different sources of protein such as beans, vegetables, dairy, seafood, and meat differ in amino acid composition. Further, the type and level of other factors, such as fatty acids and persistent organic pollutants (POPs) vary between dietary protein sources. All these factors can modulate the composition of the gut microbiota and may thereby influence their obesogenic properties. This review summarizes evidence of how different protein sources affect energy efficiency, obesity development, and the gut microbiota, linking protein-dependent changes in the gut microbiota with obesity. PMID:29311977

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.

Allometry and Ecology of the Bilaterian Gut Microbiome

PubMed Central

Sherrill-Mix, Scott; McCormick, Kevin; Lauder, Abigail; Bailey, Aubrey; Zimmerman, Laurie; Li, Yingying; Django, Jean-Bosco N.; Bertolani, Paco; Colin, Christelle; Hart, John A.; Hart, Terese B.; Georgiev, Alexander V.; Sanz, Crickette M.; Morgan, David B.; Atencia, Rebeca; Cox, Debby; Muller, Martin N.; Sommer, Volker; Piel, Alexander K.; Stewart, Fiona A.; Speede, Sheri; Roman, Joe; Wu, Gary; Taylor, Josh; Bohm, Rudolf; Rose, Heather M.; Carlson, John; Mjungu, Deus; Schmidt, Paul; Gaughan, Celeste; Bushman, Joyslin I.; Schmidt, Ella; Bittinger, Kyle; Collman, Ronald G.; Hahn, Beatrice H.

2018-01-01

ABSTRACT Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (Bilateria) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction. PMID:29588401

Wickerhamiella allomyrinae f.a., sp. nov., a yeast species isolated from the gut of the rhinoceros beetle Allomyrina dichotoma.

PubMed

Ren, Yong-Cheng; Wang, Yun; Chen, Liang; Ke, Tao; Hui, Feng-Li

2014-11-01

Two strains representing Wickerhamiella allomyrinae f.a., sp. nov. were isolated from the gut of Allomyrina dichotoma (Coleoptera: Scarabeidae) collected from the Baotianman National Nature Reserve, Nanyan, Henan Province, China. Sequence analyses of the D1/D2 domains of the LSU rRNA gene revealed that this novel species was located in the Wickerhamiella clade (Saccharomycetes, Saccharomycetales), with three described species of the genus Candida, namely Candida musiphila, Candida spandovensis and Candida sergipensis, as the most closely related species. The novel species differed from these three species by 9.3-9.8% sequence divergence (35-45 nt substitutions) in the D1/D2 sequences. The species could also be distinguished from the closely related species, C. musiphila, C. spandovensis and C. sergipensis, by growth on vitamin-free medium and at 37 °C. The type strain is Wickerhamiella allomyrinae sp. nov. NYNU 13920(T) ( =CICC 33031(T) =CBS 13167(T)). © 2014 IUMS.

AN EDUCATIONAL THEORY MODEL--(SIGGS), AN INTEGRATION OF SET THEORY, INFORMATION THEORY, AND GRAPH THEORY WITH GENERAL SYSTEMS THEORY.

ERIC Educational Resources Information Center

MACCIA, ELIZABETH S.; AND OTHERS

AN ANNOTATED BIBLIOGRAPHY OF 20 ITEMS AND A DISCUSSION OF ITS SIGNIFICANCE WAS PRESENTED TO DESCRIBE CURRENT UTILIZATION OF SUBJECT THEORIES IN THE CONSTRUCTION OF AN EDUCATIONAL THEORY. ALSO, A THEORY MODEL WAS USED TO DEMONSTRATE CONSTRUCTION OF A SCIENTIFIC EDUCATIONAL THEORY. THE THEORY MODEL INCORPORATED SET THEORY (S), INFORMATION THEORY…

Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse.

PubMed

Scott, Karen A; Ida, Masayuki; Peterson, Veronica L; Prenderville, Jack A; Moloney, Gerard M; Izumo, Takayuki; Murphy, Kiera; Murphy, Amy; Ross, R Paul; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

2017-10-01

Over the last decade, there has been increased interest in the role of the gut microbiome in health including brain health. This is by no means a new theory; Elie Metchnikoff proposed over a century ago that targeting the gut by consuming lactic acid bacteria such as those in yogurt, could improve or delay the onset of cognitive decline associated with ageing. However, there is limited information characterising the relationship between the behavioural and physiological sequelae of ageing and alterations in the gut microbiome. To this end, we assessed the behavioural, physiological and caecal microbiota profile of aged male mice. Older mice (20-21months old) exhibited deficits in spatial memory and increases in anxiety-like behaviours compared to younger mice (2-3months old). They also exhibited increased gut permeability, which was directly correlated with elevations in peripheral pro-inflammatory cytokines. Furthermore, stress exacerbated the gut permeability of aged mice. Examination of the caecal microbiota revealed significant increases in phylum TM7, family Porphyromonadaceae and genus Odoribacter of aged mice. This represents a shift of aged microbiota towards a profile previously associated with inflammatory disease, particularly gastrointestinal and liver disorders. Furthermore, Porphyromonadaceae, which has also been associated with cognitive decline and affective disorders, was directly correlated with anxiety-like behaviour in aged mice. These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioural, affective and cognitive functions seen in ageing. Copyright © 2017 Elsevier Inc. 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

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 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

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.

Modeling fMRI signals can provide insights into neural processing in the cerebral cortex.

PubMed

Vanni, Simo; Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

2015-08-01

Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals. Copyright © 2015 the American Physiological Society.

Modeling fMRI signals can provide insights into neural processing in the cerebral cortex

PubMed Central

Sharifian, Fariba; Heikkinen, Hanna; Vigário, Ricardo

2015-01-01

Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals. PMID:25972586

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.

Theoretical study on the charge transport in single crystals of TCNQ, F2-TCNQ and F4-TCNQ.

PubMed

Ji, Li-Fei; Fan, Jian-Xun; Zhang, Shou-Feng; Ren, Ai-Min

2018-01-31

2,5-Difluoro-7,7,8,8-tetracyanoquinodimethane (F 2 -TCNQ) was recently reported to display excellent electron transport properties in single crystal field-effect transistors (FETs). Its carrier mobility can reach 25 cm 2 V -1 s -1 in devices. However, its counterparts TCNQ and F 4 -TCNQ (tetrafluoro-7,7,8,8-tetracyanoquinodimethane) do not exhibit the same highly efficient behavior. To better understand this significant difference in charge carrier mobility, a multiscale approach combining semiclassical Marcus hopping theory, a quantum nuclear enabled hopping model and molecular dynamics simulations was performed to assess the electron mobilities of the F n -TCNQ (n = 0, 2, 4) systems in this work. The results indicated that the outstanding electron transport behavior of F 2 -TCNQ arises from its effective 3D charge carrier percolation network due to its special packing motif and the nuclear tunneling effect. Moreover, the poor transport properties of TCNQ and F 4 -TCNQ stem from their invalid packing and strong thermal disorder. It was found that Marcus theory underestimated the mobilities for all the systems, while the quantum model with the nuclear tunneling effect provided reasonable results compared to experiments. Moreover, the band-like transport behavior of F 2 -TCNQ was well described by the quantum nuclear enabled hopping model. In addition, quantum theory of atoms in molecules (QTAIM) analysis and symmetry-adapted perturbation theory (SAPT) were used to characterize the intermolecular interactions in TCNQ, F 2 -TCNQ and F 4 -TCNQ crystals. A primary understanding of various noncovalent interaction responses for crystal formation is crucial to understand the structure-property relationships in organic molecular materials.

Antibiotic-induced changes in the microbiota disrupt redox dynamics in the gut

PubMed Central

Reese, Aspen T; Cho, Eugenia H; Klitzman, Bruce; Nichols, Scott P; Wisniewski, Natalie A; Villa, Max M; Durand, Heather K; Jiang, Sharon; Midani, Firas S; Nimmagadda, Sai N; O'Connell, Thomas M; Wright, Justin P; Deshusses, Marc A

2018-01-01

How host and microbial factors combine to structure gut microbial communities remains incompletely understood. Redox potential is an important environmental feature affected by both host and microbial actions. We assessed how antibiotics, which can impact host and microbial function, change redox state and how this contributes to post-antibiotic succession. We showed gut redox potential increased within hours of an antibiotic dose in mice. Host and microbial functioning changed under treatment, but shifts in redox potentials could be attributed specifically to bacterial suppression in a host-free ex vivo human gut microbiota model. Redox dynamics were linked to blooms of the bacterial family Enterobacteriaceae. Ecological succession to pre-treatment composition was associated with recovery of gut redox, but also required dispersal from unaffected gut communities. As bacterial competition for electron acceptors can be a key ecological factor structuring gut communities, these results support the potential for manipulating gut microbiota through managing bacterial respiration. PMID:29916366

An Integrated Higgs Force Theory

NASA Astrophysics Data System (ADS)

Colella, Antonio

2016-03-01

An Integrated Higgs force theory (IHFT) was based on 2 key requirement amplifications: a matter particle/Higgs force was one and inseparable; a matter particle/Higgs force bidirectionally condensed/evaporated from/to super force. These were basis of 5 theories: particle creation, baryogenesis, superpartner/quark decays, spontaneous symmetry breaking, and stellar black holes. Our universe's 129 matter/force particles contained 64 supersymmetric Higgs particles; 9 transient matter particles/Higgs forces decayed to 8 permanent matter particles/Higgs forces; mass was given to a matter particle by its Higgs force and gravitons; and sum of 8 Higgs force energies of 8 permanent matter particles was dark energy. An IHFT's essence is the intimate physical relationships between 8 theories. These theories are independent because physicists in one theory worked independently of physicists in the other seven. An IHFT's premise is without sacrificing their integrities, 8 independent existing theories are replaced by 8 interrelated amplified theories. Requirement amplifications provide interfaces between the 8 theories. Intimate relationships between 8 theories including the above 5 and string, Higgs forces, and Super Universe are described. The sorting category selected was F. PARTICLES AND FIELDS (e.g., F1 Higgs Physics, F10 Alternative Beyond the Standard Model Physics, F11 Dark Sector Theories and Searches, and F12 Particle Cosmology).

Gut microbiome in type 1 diabetes: A comprehensive review.

PubMed

Zheng, Peilin; Li, Zhixia; Zhou, Zhiguang

2018-06-21

Type 1 diabetes (T1D) is an autoimmune disease, which is characterized by the destruction of islet β cells in the pancreas triggered by genetic and environmental factors. In past decades, extensive familial and genome-wide association studies have revealed more than 50 risk loci in the genome. However, genetic susceptibility cannot explain the increased incidence of T1D worldwide, which is very likely attributed by the growing impact of environmental factors, especially gut microbiome. Recently, the role of gut microbiome in the pathogenesis of T1D have been uncovered by the increasing evidence from both human subjects and animal models, strongly indicating that gut microbiome might be a pivotal hub of T1D-triggering factors, especially environmental factors. In this review, we summarize the current etiological and mechanism studies of gut microbiome in T1D. A better understanding of the role of gut microbiome in T1D may provide us with powerful prognostic and therapeutic tools in the near future. This article is protected by copyright. All rights reserved.

Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

PubMed

Bowe, Whitney P; Logan, Alan C

2011-01-31

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne.

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

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.

Cosmic transit and anisotropic models in f(R,T) gravity

NASA Astrophysics Data System (ADS)

Sahu, S. K.; Tripathy, S. K.; Sahoo, P. K.; Nath, A.

2017-06-01

Accelerating cosmological models are constructed in a modified gravity theory dubbed as $f(R,T)$ gravity at the backdrop of an anisotropic Bianchi type-III universe. $f(R,T)$ is a function of the Ricci scalar $R$ and the trace $T$ of the energy-momentum tensor and it replaces the Ricci scalar in the Einstein-Hilbert action of General Relativity. The models are constructed for two different ways of modification of the Einstein-Hilbert action. Exact solutions of the field equations are obtained by a novel method of integration. We have explored the behaviour of the cosmic transit from an decelerated phase of expansion to an accelerated phase to get the dynamical features of the universe. Within the formalism of the present work, it is found that, the modification of the Einstein-Hilbert action does not affect the scale factor. However the dynamics of the effective dark energy equation of state is significantly affected.

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

Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model.

PubMed

Tsilimigras, Matthew C B; Gharaibeh, Raad Z; Sioda, Michael; Gray, Laura; Fodor, Anthony A; Lyte, Mark

2018-05-01

Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort. CF-1 mice underwent alternating days of restraint and forced swim for 19 days (male n = 8, female n = 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated. Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p = .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected. These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.

Wilsonian dark matter in string derived Z' model

NASA Astrophysics Data System (ADS)

Delle Rose, L.; Faraggi, A. E.; Marzo, C.; Rizos, J.

2017-09-01

The dark matter issue is among the most perplexing in contemporary physics. The problem is more enigmatic due to the wide range of possible solutions, ranging from the ultralight to the supermassive. String theory gives rise to plausible dark matter candidates due to the breaking of the non-Abelian grand unified theory (GUT) symmetries by Wilson lines. The physical spectrum then contains states that do not satisfy the quantization conditions of the unbroken GUT symmetry. Given that the Standard Model states are identified with broken GUT representations, and provided that any ensuing symmetry breakings are induced by components of GUT states, a remnant discrete symmetry remains that forbids the decay of the Wilsonian states. A class of such states are obtained in a heterotic-string-derived Z' model. The model exploits the spinor-vector duality symmetry, observed in the fermionic Z2×Z2 heterotic-string orbifolds, to generate a Z'∈E6 symmetry that may remain unbroken down to low energies. The E6 symmetry is broken at the string level with discrete Wilson lines. The Wilsonian dark matter candidates in the string-derived model are S O (10 ), and hence Standard Model, singlets and possess non-E6 U(1)Z' charges. Depending on the U(1)Z' breaking scale and the reheating temperature they give rise to different scenarios for the relic abundance, and are in accordance with the cosmological constraints.

Allometry and Ecology of the Bilaterian Gut Microbiome.

PubMed

Sherrill-Mix, Scott; McCormick, Kevin; Lauder, Abigail; Bailey, Aubrey; Zimmerman, Laurie; Li, Yingying; Django, Jean-Bosco N; Bertolani, Paco; Colin, Christelle; Hart, John A; Hart, Terese B; Georgiev, Alexander V; Sanz, Crickette M; Morgan, David B; Atencia, Rebeca; Cox, Debby; Muller, Martin N; Sommer, Volker; Piel, Alexander K; Stewart, Fiona A; Speede, Sheri; Roman, Joe; Wu, Gary; Taylor, Josh; Bohm, Rudolf; Rose, Heather M; Carlson, John; Mjungu, Deus; Schmidt, Paul; Gaughan, Celeste; Bushman, Joyslin I; Schmidt, Ella; Bittinger, Kyle; Collman, Ronald G; Hahn, Beatrice H; Bushman, Frederic D

2018-03-27

Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals ( Bilateria ) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction. IMPORTANCE The intestinal microbiome of animals is essential for health, contributing to digestion of foods, proper immune development, inhibition of pathogen colonization, and catabolism of xenobiotic

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

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

The Green-Schwarz mechanism and geometric anomaly relations in 2d (0,2) F-theory vacua

NASA Astrophysics Data System (ADS)

Weigand, Timo; Xu, Fengjun

2018-04-01

We study the structure of gauge and gravitational anomalies in 2d N = (0 , 2) theories obtained by compactification of F-theory on elliptically fibered Calabi-Yau 5-folds. Abelian gauge anomalies, induced at 1-loop in perturbation theory, are cancelled by a generalized Green-Schwarz mechanism operating at the level of chiral scalar fields in the 2d supergravity theory. We derive closed expressions for the gravitational and the non-abelian and abelian gauge anomalies including the Green-Schwarz counterterms. These expressions involve topological invariants of the underlying elliptic fibration and the gauge background thereon. Cancellation of anomalies in the effective theory predicts intricate topological identities which must hold on every elliptically fibered Calabi-Yau 5-fold. We verify these relations in a non-trivial example, but their proof from a purely mathematical perspective remains as an interesting open problem. Some of the identities we find on elliptic 5-folds are related in an intriguing way to previously studied topological identities governing the structure of anomalies in 6d N = (1 , 0) and 4d N = 1 theories obtained from F-theory.

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.

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.

General topology meets model theory, on and

PubMed Central

Malliaris, Maryanthe; Shelah, Saharon

2013-01-01

Cantor proved in 1874 [Cantor G (1874) J Reine Angew Math 77:258–262] that the continuum is uncountable, and Hilbert’s first problem asks whether it is the smallest uncountable cardinal. A program arose to study cardinal invariants of the continuum, which measure the size of the continuum in various ways. By Gödel [Gödel K (1939) Proc Natl Acad Sci USA 25(4):220–224] and Cohen [Cohen P (1963) Proc Natl Acad Sci USA 50(6):1143–1148], Hilbert’s first problem is independent of ZFC (Zermelo-Fraenkel set theory with the axiom of choice). Much work both before and since has been done on inequalities between these cardinal invariants, but some basic questions have remained open despite Cohen’s introduction of forcing. The oldest and perhaps most famous of these is whether “,” which was proved in a special case by Rothberger [Rothberger F (1948) Fund Math 35:29–46], building on Hausdorff [Hausdorff (1936) Fund Math 26:241–255]. In this paper we explain how our work on the structure of Keisler’s order, a large-scale classification problem in model theory, led to the solution of this problem in ZFC as well as of an a priori unrelated open question in model theory. PMID:23836659

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.

Causality Analysis of fMRI Data Based on the Directed Information Theory Framework.

PubMed

Wang, Zhe; Alahmadi, Ahmed; Zhu, David C; Li, Tongtong

2016-05-01

This paper aims to conduct fMRI-based causality analysis in brain connectivity by exploiting the directed information (DI) theory framework. Unlike the well-known Granger causality (GC) analysis, which relies on the linear prediction technique, the DI theory framework does not have any modeling constraints on the sequences to be evaluated and ensures estimation convergence. Moreover, it can be used to generate the GC graphs. In this paper, first, we introduce the core concepts in the DI framework. Second, we present how to conduct causality analysis using DI measures between two time series. We provide the detailed procedure on how to calculate the DI for two finite-time series. The two major steps involved here are optimal bin size selection for data digitization and probability estimation. Finally, we demonstrate the applicability of DI-based causality analysis using both the simulated data and experimental fMRI data, and compare the results with that of the GC analysis. Our analysis indicates that GC analysis is effective in detecting linear or nearly linear causal relationship, but may have difficulty in capturing nonlinear causal relationships. On the other hand, DI-based causality analysis is more effective in capturing both linear and nonlinear causal relationships. Moreover, it is observed that brain connectivity among different regions generally involves dynamic two-way information transmissions between them. Our results show that when bidirectional information flow is present, DI is more effective than GC to quantify the overall causal relationship.

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

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.

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.

Honeybee gut microbiota promotes host weight gain via bacterial metabolism and hormonal signaling

PubMed Central

Powell, J. Elijah; Steele, Margaret I.; Dietrich, Carsten; Moran, Nancy A.

2017-01-01

Social bees harbor a simple and specialized microbiota that is spatially organized into different gut compartments. Recent results on the potential involvement of bee gut communities in pathogen protection and nutritional function have drawn attention to the impact of the microbiota on bee health. However, the contributions of gut microbiota to host physiology have yet to be investigated. Here we show that the gut microbiota promotes weight gain of both whole body and the gut in individual honey bees. This effect is likely mediated by changes in host vitellogenin, insulin signaling, and gustatory response. We found that microbial metabolism markedly reduces gut pH and redox potential through the production of short-chain fatty acids and that the bacteria adjacent to the gut wall form an oxygen gradient within the intestine. The short-chain fatty acid profile contributed by dominant gut species was confirmed in vitro. Furthermore, metabolomic analyses revealed that the gut community has striking impacts on the metabolic profiles of the gut compartments and the hemolymph, suggesting that gut bacteria degrade plant polymers from pollen and that the resulting metabolites contribute to host nutrition. Our results demonstrate how microbial metabolism affects bee growth, hormonal signaling, behavior, and gut physicochemical conditions. These findings indicate that the bee gut microbiota has basic roles similar to those found in some other animals and thus provides a model in studies of host–microbe interactions. PMID:28420790

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.

Gut microbiota functions: metabolism of nutrients and other food components.

PubMed

Rowland, Ian; Gibson, Glenn; Heinken, Almut; Scott, Karen; Swann, Jonathan; Thiele, Ines; Tuohy, Kieran

2018-02-01

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays.

Isotropic LQC and LQC-inspired models with a massless scalar field as generalised Brans-Dicke theories

NASA Astrophysics Data System (ADS)

Rama, S. Kalyana

2018-06-01

We explore whether generalised Brans-Dicke theories, which have a scalar field Φ and a function ω (Φ ), can be the effective actions leading to the effective equations of motion of the LQC and the LQC-inspired models, which have a massless scalar field σ and a function f( m). We find that this is possible for isotropic cosmology. We relate the pairs (σ , f) and (Φ , ω ) and, using examples, illustrate these relations. We find that near the bounce of the LQC evolutions for which f(m) = sin m, the corresponding field Φ → 0 and the function ω (Φ ) ∝ Φ ^2. We also find that the class of generalised Brans-Dicke theories, which we had found earlier to lead to non singular isotropic evolutions, may be written as an LQC-inspired model. The relations found here in the isotropic cases do not apply to the anisotropic cases, which perhaps require more general effective actions.

Gut Microbiota in a Rat Oral Sensitization Model: Effect of a Cocoa-Enriched Diet

PubMed Central

Camps-Bossacoma, Mariona; Pérez-Cano, Francisco J.; Franch, Àngels

2017-01-01

Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota. Lewis rats were orally sensitized and fed with either a standard or 10% cocoa diet. Faecal microbiota was analysed through metagenomics study. Intestinal IgA concentration was also determined. Oral sensitization produced few changes in intestinal microbiota, but in those rats fed a cocoa diet significant modifications appeared. Decreased bacteria from the Firmicutes and Proteobacteria phyla and a higher percentage of bacteria belonging to the Tenericutes and Cyanobacteria phyla were observed. In conclusion, a cocoa diet is able to modify the microbiota bacterial pattern in orally sensitized animals. As cocoa inhibits the synthesis of specific antibodies and also intestinal IgA, those changes in microbiota pattern, particularly those of the Proteobacteria phylum, might be partially responsible for the tolerogenic effect of cocoa. PMID:28239436

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.

Density functional theory of electron transfer beyond the Born-Oppenheimer approximation: Case study of LiF.

PubMed

Li, Chen; Requist, Ryan; Gross, E K U

2018-02-28

We perform model calculations for a stretched LiF molecule, demonstrating that nonadiabatic charge transfer effects can be accurately and seamlessly described within a density functional framework. In alkali halides like LiF, there is an abrupt change in the ground state electronic distribution due to an electron transfer at a critical bond length R = R c , where an avoided crossing of the lowest adiabatic potential energy surfaces calls the validity of the Born-Oppenheimer approximation into doubt. Modeling the R-dependent electronic structure of LiF within a two-site Hubbard model, we find that nonadiabatic electron-nuclear coupling produces a sizable elongation of the critical R c by 0.5 bohr. This effect is very accurately captured by a simple and rigorously derived correction, with an M -1 prefactor, to the exchange-correlation potential in density functional theory, M = reduced nuclear mass. Since this nonadiabatic term depends on gradients of the nuclear wave function and conditional electronic density, ∇ R χ(R) and ∇ R n(r, R), it couples the Kohn-Sham equations at neighboring R points. Motivated by an observed localization of nonadiabatic effects in nuclear configuration space, we propose a local conditional density approximation-an approximation that reduces the search for nonadiabatic density functionals to the search for a single function y(n).

Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus

PubMed Central

Moreno-Indias, Isabel; Cardona, Fernando; Tinahones, Francisco J.; Queipo-Ortuño, María Isabel

2014-01-01

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gut microbiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gut microbiota in the pathogenesis of obesity and type 2 diabetes mellitus (TDM2). The establishment of gut microbiota is dependent on the type of birth. With effect from this point, gut microbiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gut microbiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or TDM2. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases. PMID:24808896

Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus.

PubMed

Moreno-Indias, Isabel; Cardona, Fernando; Tinahones, Francisco J; Queipo-Ortuño, María Isabel

2014-01-01

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gut microbiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gut microbiota in the pathogenesis of obesity and type 2 diabetes mellitus (TDM2). The establishment of gut microbiota is dependent on the type of birth. With effect from this point, gut microbiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gut microbiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or TDM2. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases.

Molecular cloning, characterization and mRNA expression of duck interleukin-17F

USDA-ARS?s Scientific Manuscript database

Interleukin-17F (IL-17F) is a proinflammatory cytokine that plays an important role in gut homeostasis. A full-length duck IL-17F (duIL-17F) cDNA with a 501-bp coding region was identified in ConA-activated splenic lymphocytes. duIL-17F is predicted to encode 166 amino acids, including a 26-amino ...

High-pressure and high-temperature physical properties of LiF studied by density functional theory calculations and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sun, Xiao-Wei; Liu, Zi-Jiang; Quan, Wei-Long; Song, Ting; Khenata, Rabah; Bin-Omran, Saad

2018-05-01

Using the revised Perdew-Burke-Ernzerhof generalized gradient approximation based on first-principles plane-wave pseudopotential density functional theory, the high-pressure structural phase transition of LiF is explored. From the analysis of Gibbs free energies, we find that no phase transition occurs for LiF in the presented pressure range from 0 to 1000 GPa, and this result is consistent with the theoretical prediction obtained via ab initio calculations [N.A. Smirnov, Phys. Rev. B 83 (2011) 014109]. Using the classical molecular dynamics technique with effective pair potentials which consist of the Coulomb, dispersion, and repulsion interaction, the melting phase diagram of LiF is determined. The obtained normalized volumes under pressure are in good agreement with our density functional theory results and the available experimental data. Meanwhile, with the help of the quasi-harmonic Debye model in which the phononic effects are considered, the thermodynamic properties of interest, including the volume thermal expansion coefficient, isothermal bulk modulus and its first and second pressure derivatives, heat capacity at constant volume, entropy, Debye temperature, and Grüneisen parameter of LiF are predicted systematically. All the properties of LiF with the stable NaCl-type structure in the temperature range of 0-4900 K and the pressure up to 1000 GPa are summarized.

Acne vulgaris, probiotics and the gut-brain-skin axis - back to the future?

PubMed Central

2011-01-01

Over 70 years have passed since dermatologists John H. Stokes and Donald M. Pillsbury first proposed a gastrointestinal mechanism for the overlap between depression, anxiety and skin conditions such as acne. Stokes and Pillsbury hypothesized that emotional states might alter the normal intestinal microflora, increase intestinal permeability and contribute to systemic inflammation. Among the remedies advocated by Stokes and Pillsbury were Lactobacillus acidophilus cultures. Many aspects of this gut-brain-skin unifying theory have recently been validated. The ability of the gut microbiota and oral probiotics to influence systemic inflammation, oxidative stress, glycemic control, tissue lipid content and even mood itself, may have important implications in acne. The intestinal microflora may also provide a twist to the developing diet and acne research. Here we provide a historical perspective to the contemporary investigations and clinical implications of the gut-brain-skin connection in acne. PMID:21281494

Geomorphic Unit Tool (GUT): Applications of Fluvial Mapping

NASA Astrophysics Data System (ADS)

Kramer, N.; Bangen, S. G.; Wheaton, J. M.; Bouwes, N.; Wall, E.; Saunders, C.; Bennett, S.; Fortney, S.

2017-12-01

Geomorphic units are the building blocks of rivers and represent distinct habitat patches for many fluvial organisms. We present the Geomorphic Unit Toolkit (GUT), a flexible GIS geomorphic unit mapping tool, to generate maps of fluvial landforms from topography. GUT applies attributes to landforms based on flow stage (Tier 1), topographic signatures (Tier 2), geomorphic characteristics (Tier 3) and patch characteristics (Tier 4) to derive attributed maps at the level of detail required by analysts. We hypothesize that if more rigorous and consistent geomorphic mapping is conducted, better correlations between physical habitat units and ecohydraulic model results will be obtained compared to past work. Using output from GUT for coarse bed tributary streams in the Columbia River Basin, we explore relationships between salmonid habitat and geomorphic spatial metrics. We also highlight case studies of how GUT can be used to showcase geomorphic impact from large wood restoration efforts. Provided high resolution topography exists, this tool can be used to quickly assess changes in fluvial geomorphology in watersheds impacted by human activities.

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

Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease of main metabolites

PubMed Central

Dostal, Alexandra; Fehlbaum, Sophie; Chassard, Christophe; Zimmermann, Michael Bruce; Lacroix, Christophe

2012-01-01

Iron (Fe) deficiency affects an estimated 2 billion people worldwide and Fe supplements are a common corrective strategy. The impact of Fe deficiency and Fe supplementation on the complex microbial community of the child gut was studied using in vitro colonic fermentation models inoculated with immobilized fecal microbiota. Chyme media (all Fe chelated by 2,2’-dipyridyl to 26.5 mg Fe L-1) mimicking Fe deficiency and supplementation were continuously fermented. Fermentation effluent samples were analyzed daily on the microbial composition and metabolites by qPCR, 16S rRNA gene 454-pyrosequencing and HPLC. Low Fe conditions (1.56 mg Fe L-1) significantly decreased acetate concentrations and subsequent Fe supplementation (26.5 mg Fe L-1) restored acetate production. High Fe following normal Fe conditions had no impact on the gut microbiota composition and metabolic activity. During very low Fe conditions (0 . 9 m g F e L-1 or Fe chelated b y 2,2’-dipyridyl), a decrease of Roseburia spp./Eubacterium rectale, Clostridium Cluster IV members and Bacteroides spp. was observed while Lactobacillus spp. and Enterobacteriaceae increased consistent with a decrease of butyrate (-84%) and propionate (-55%). The strong dysbiosis of the gut microbiota together with decrease of main gut microbiota metabolites observed with very low iron conditions could weaken the barrier effect of the microbiota and negatively impact gut health. PMID:22845175

Cosmological implications of scalar field dark energy models in f(T,𝒯 ) gravity

NASA Astrophysics Data System (ADS)

Salako, Ines G.; Jawad, Abdul; Moradpour, Hooman

After reviewing the f(T,𝒯 ) gravity, in which T is the torsion scalar and 𝒯 is the trace of the energy-momentum tensor, we refer to two cosmological models of this theory in agreement with observational data. Thereinafter, we consider a flat Friedmann-Robertson-Walker (FRW) universe filled by a pressureless source and look at the terms other than the Einstein terms in the corresponding Friedmann equations, as the dark energy (DE) candidate. In addition, some cosmological features of models, including equation of states and deceleration parameters, are addressed helping us in getting the accelerated expansion of the universe in quintessence era. Finally, we extract the scalar field as well as potential of quintessence, tachyon, K-essence and dilatonic fields for both f(T,𝒯 ) models. It is observed that the dynamics of scalar field as well as the scalar potential of these models indicate an accelerated expanding universe in these models.

The hidden flat like universe. Starobinsky-like inflation induced by f (T) gravity

NASA Astrophysics Data System (ADS)

El Hanafy, W.; Nashed, G. G. L.

2015-06-01

We study a single-fluid component in a flat like universe (FLU) governed by f( T) gravity theories, where T is the teleparallel torsion scalar. The FLU model, regardless of the value of the spatial curvature k, identifies a special class of f( T) gravity theories. Remarkably, FLU f( T) gravity does not reduce to teleparallel gravity theory. In large Hubble spacetime the theory is consistent with the inflationary universe scenario and respects the conservation principle. The equation of state evolves similarly in all models . We study the case when the torsion tensor consists of a scalar field, which enables to derive a quintessence potential from the obtained f( T) gravity theory. The potential produces Starobinsky-like model naturally without using a conformal transformation, with higher orders continuously interpolate between Starobinsky and quadratic inflation models. The slow-roll analysis shows double solutions, so that for a single value of the scalar tilt (spectral index) the theory can predict double tensor-to-scalar ratios r of E-mode and B-mode polarizations.

Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

PubMed

Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

2018-05-01

Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

big bang gene modulates gut immune tolerance in Drosophila.

PubMed

Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

2013-02-19

Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan.

PubMed

Bäuerl, C; Collado, M C; Diaz Cuevas, A; Viña, J; Pérez Martínez, G

2018-06-01

Alzheimer's disease (AD) is the most common form of dementia and one of the major causes of disability and dependency in older people. Accumulating evidences link gut microbiota with different diseases and its relationship with neurodegenerative diseases is becoming most intriguing. This study was aimed to compare the gut microbiota of transgenic APP/PS1 (TG) mice, a well-established deterministic mouse model of AD, with their C57BL/6 wild-type (WT) littermates. Faecal samples were collected from 3-, 6- and 24-month-old mice and analysed by pyrosequencing of the V1-V3 region of the bacterial 16S rRNA genes. Bacterial profiles were similar in all young mice (3 months old), and started to diverge so that 6-month-old WT and TG mice had different and more diverse microbiota. During ageing, Turicibacteriaceae (typical mice bacterial group) and Rikenellaceae increased in all groups, although total Bacteroidetes remained stable. TG mice were characterized by an increase in Proteobacteria after 6 months, particularly the genus Sutterella (Betaproteobacteria), interestingly also increased in autism disorder. Also, the inflammation related family Erysipelotrichaceae was more abundant in TG mice at 24 months compared to wild-type control. In summary, AD pathology in mice shifts the gut microbiota towards profiles that share features with autism and inflammatory disorders. Alzheimer's disease is a neurodegenerative disease and neuroinflammation in the central nervous system appears to have a pivotal role. Using the transgenic APP/PS1 (TG) mouse model, we successfully characterized how AD pathology shifted gut microbiota composition during ageing towards an inflammation related bacterial profile related to Proteobacteria and Erysipelotrichaceae and suggest that these changes could contribute to disease progression and severity. Microbiota-targeted interventions could therefore represent a strategy to postpone disease symptoms. © 2018 The Society for Applied Microbiology.

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.

Gut microbiota modify risk for dietary glycemia-induced age-related macular degeneration.

PubMed

Rowan, Sheldon; Taylor, Allen

2018-03-21

Age-related macular degeneration (AMD) is a leading cause of blindness world-wide. Although the etiology of AMD is multifactorial, diet and nutrition have strong epidemiologic associations with disease onset and progression. Recent studies indicate a role for gut microbiota in development of AMD in mouse models and in some forms of human AMD. We previously found that consuming lower glycemia diets is associated with protection against AMD in humans and switching from higher to lower glycemia diets arrests AMD phenotypes in mice. Gut microbiota populations and circulating microbial cometabolites were altered in response to dietary carbohydrates, indicating a gut-retina axis. Here we explore additional gut microbiota-AMD interactions that point toward pathogenic roles for some gut microbiota families, including Ruminococcaceae and Lachnospiraceae, and individual members of Turicibacteraceae, Clostridiaceae, and Mogibacteriaceae. We also speculate on potential mechanisms by which gut microbiota influence AMD, with the objective of devising new AMD diagnoses and treatments.

Low calorie sweeteners: Evidence remains lacking for effects on human gut function.

PubMed

Bryant, Charlotte; Mclaughlin, John

2016-10-01

The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars. Copyright © 2016. Published by Elsevier Inc.

Disentangling the f(R)-duality

NASA Astrophysics Data System (ADS)

Broy, Benedict J.; Pedro, Francisco G.; Westphal, Alexander

2015-03-01

Motivated by UV realisations of Starobinsky-like inflation models, we study generic exponential plateau-like potentials to understand whether an exact f(R)-formulation may still be obtained when the asymptotic shift-symmetry of the potential is broken for larger field values. Potentials which break the shift symmetry with rising exponentials at large field values only allow for corresponding f(R)-descriptions with a leading order term Rn with 1f(R) and thus cannot maintain a plateau for all field values. We further find a lean and instructive way to obtain a function f(R) describing m2phi2-inflation which breaks the shift symmetry with a monomial, and corresponds to effectively logarithmic corrections to an R+R2 model. These examples emphasise that higher order terms in f(R)-theory may not be neglected if they are present at all. Additionally, we relate the function f(R) corresponding to chaotic inflation to a more general Jordan frame set-up. In addition, we consider f(R)-duals of two given UV examples, both from supergravity and string theory. Finally, we outline the CMB phenomenology of these models which show effects of power suppression at low-l.

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.

Gut microbiota and obesity: role in aetiology and potential therapeutic target.

PubMed

Moran, Carthage P; Shanahan, Fergus

2014-08-01

Obesity is epidemic; chronic energy surplus is clearly important in obesity development but other factors are at play. Indigenous gut microbiota are implicated in the aetiopathogenesis of obesity and obesity-related disorders. Evidence from murine models initially suggested a role for the gut microbiota in weight regulation and the microbiota has been shown to contribute to the low grade inflammation that characterises obesity. The microbiota and its metabolites mediate some of the alterations of the microbiota-gut-brain axis, the endocannabinoid system, and bile acid metabolism, found in obesity-related disorders. Modulation of the gut microbiota is an attractive proposition for prevention or treatment of obesity, particularly as traditional measures have been sub-optimal. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spatial organization of a model 15-member human gut microbiota established in gnotobiotic mice

PubMed Central

Mark Welch, Jessica L.; Hasegawa, Yuko; McNulty, Nathan P.; Gordon, Jeffrey I.; Borisy, Gary G.

2017-01-01

Knowledge of the spatial organization of the gut microbiota is important for understanding the physical and molecular interactions among its members. These interactions are thought to influence microbial succession, community stability, syntrophic relationships, and resiliency in the face of perturbations. The complexity and dynamism of the gut microbiota pose considerable challenges for quantitative analysis of its spatial organization. Here, we illustrate an approach for addressing this challenge, using (i) a model, defined 15-member consortium of phylogenetically diverse, sequenced human gut bacterial strains introduced into adult gnotobiotic mice fed a polysaccharide-rich diet, and (ii) in situ hybridization and spectral imaging analysis methods that allow simultaneous detection of multiple bacterial strains at multiple spatial scales. Differences in the binding affinities of strains for substrates such as mucus or food particles, combined with more rapid replication in a preferred microhabitat, could, in principle, lead to localized clonally expanded aggregates composed of one or a few taxa. However, our results reveal a colonic community that is mixed at micrometer scales, with distinct spatial distributions of some taxa relative to one another, notably at the border between the mucosa and the lumen. Our data suggest that lumen and mucosa in the proximal colon should be conceptualized not as stratified compartments but as components of an incompletely mixed bioreactor. Employing the experimental approaches described should allow direct tests of whether and how specified host and microbial factors influence the nature and functional contributions of “microscale” mixing to the dynamic operations of the microbiota in health and disease. PMID:29073107

Human Gut Microbiome: Function Matters.

PubMed

Heintz-Buschart, Anna; Wilmes, Paul

2017-11-22

The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. Copyright © 2017 Elsevier Ltd. All rights reserved.

Broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model.

PubMed

Strzępa, Anna; Majewska-Szczepanik, Monika; Lobo, Francis M; Wen, Li; Szczepanik, Marian

2017-07-01

Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Oral treatment with enrofloxacin suppresses CS and production of anti-trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides-Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

Stellar equilibrium configurations of compact stars in f ( R , T ) theory of gravity

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

Moraes, P.H.R.S.; Arbañil, José D.V.; Malheiro, M., E-mail: moraes.phrs@gmail.com, E-mail: arbanil@ita.br, E-mail: malheiro@ita.br

In this article we study the hydrostatic equilibrium configuration of neutron stars and strange stars, whose fluid pressure is computed from the equations of state p =ωρ{sup 5/3} and p =0.28(ρ−4B), respectively, with ω and B being constants and ρ the energy density of the fluid. We start by deriving the hydrostatic equilibrium equation for the f ( R , T ) theory of gravity, with R and T standing for the Ricci scalar and trace of the energy-momentum tensor, respectively. Such an equation is a generalization of the one obtained from general relativity, and the latter can be retrievedmore » for a certain limit of the theory. For the f ( R , T )= R +2λ T functional form, with λ being a constant, we find that some physical properties of the stars, such as pressure, energy density, mass and radius, are affected when λ is changed. We show that for a fixed central star energy density, the mass of neutron and strange stars can increase with λ. Concerning the star radius, it increases for neutron stars and it decreases for strange stars with the increment of λ. Thus, in f ( R , T ) theory of gravity we can push the maximum mass above the observational limits. This implies that the equation of state cannot be eliminated if the maximum mass within General Relativity lies below the limit given by observed pulsars.« less

Stellar equilibrium configurations of compact stars in f(R,T) theory of gravity

NASA Astrophysics Data System (ADS)

Moraes, P. H. R. S.; Arbañil, José D. V.; Malheiro, M.

2016-06-01

In this article we study the hydrostatic equilibrium configuration of neutron stars and strange stars, whose fluid pressure is computed from the equations of state p=ωρ5/3 and p=0.28(ρ-4Script B), respectively, with ω and Script B being constants and ρ the energy density of the fluid. We start by deriving the hydrostatic equilibrium equation for the f(R,T) theory of gravity, with R and T standing for the Ricci scalar and trace of the energy-momentum tensor, respectively. Such an equation is a generalization of the one obtained from general relativity, and the latter can be retrieved for a certain limit of the theory. For the f(R,T)=R+2λ T functional form, with λ being a constant, we find that some physical properties of the stars, such as pressure, energy density, mass and radius, are affected when λ is changed. We show that for a fixed central star energy density, the mass of neutron and strange stars can increase with λ. Concerning the star radius, it increases for neutron stars and it decreases for strange stars with the increment of λ. Thus, in f(R,T) theory of gravity we can push the maximum mass above the observational limits. This implies that the equation of state cannot be eliminated if the maximum mass within General Relativity lies below the limit given by observed pulsars.

Nonalcoholic fatty liver disease: for better or worse, blame the gut microbiota?

PubMed

Li, Ding-You; Yang, Min; Edwards, Sarah; Ye, Shui-Qing

2013-11-01

Nonalcoholic fatty liver disease (NAFLD) is a major clinical consequence for people with obesity and metabolic syndrome and is also associated with enteral and parenteral nutrition. Early studies suggested that altered gut microbiota might contribute to obesity by affecting energy harvest from the diet and energy storage in the host. Recent evidence in humans as well as in animal models has linked gut microbiota to the development of NAFLD through the gut-liver axis. With bacterial overgrowth and increased intestinal permeability observed in patients with NAFLD and in animal models, gut-derived bacterial products such as endotoxin (lipopolysaccharide) and bacterial DNA are being delivered to the liver through the portal vein and then activate Toll-like receptors (TLRs), mainly TLR4 and TLR9, and their downstream cytokines and chemokines, leading to the development and progression of NAFLD. Given the limited data in humans, the role of gut microbiota in the pathogenesis of NAFLD is still open to discussion. Prebiotics and probiotics have been attempted to modify the microbiota as preventive or therapeutic strategies on this pathological condition. Their beneficial effects on NALFD have been demonstrated in animal models and limited human studies. However, prospective, appropriately powered, randomized, controlled clinical trials are needed to determine whether prebiotics and probiotics and other integrated strategies to modify intestinal microbiota are efficacious therapeutic modalities to treat NALFD.

Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure

PubMed Central

Kim, Seungbum; Goel, Ruby; Kumar, Ashok; Qi, Yanfei; Lobaton, Gil; Hosaka, Koji; Mohammed, Mohammed; Handberg, Eileen M.; Richards, Elaine M.; Pepine, Carl J.; Raizada, Mohan K.

2018-01-01

Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut–epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R2 = 0.5301, P<0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R2 = 0.4608, P<0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN. PMID:29507058

Dark-energy cosmological models in f(G) gravity

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

Shamir, M. F., E-mail: farasat.shamir@nu.edu.pk

We discuss dark-energy cosmological models in f(G) gravity. For this purpose, a locally rotationally symmetric Bianchi type I cosmological model is considered. First, exact solutions with a well-known form of the f(G) model are explored. One general solution is discussed using a power-law f(G) gravity model and physical quantities are calculated. In particular, Kasner’s universe is recovered and the corresponding f(G) gravity models are reported. Second, the energy conditions for the model under consideration are discussed using graphical analysis. It is concluded that solutions with f(G) = G{sup 5/6} support expansion of universe while those with f(G) = G{sup 1/2}more » do not favor the current expansion.« less

The Gut of Geographically Disparate Ciona intestinalis Harbors a Core Microbiota

DOE PAGES

Dishaw, Larry J.; Flores-Torres, Jaime; Lax, Simon; ...

2014-04-02

It is now widely understood that all animals engage in complex interactions with bacteria (or microbes) throughout their various life stages. This ancient exchange can involve cooperation and has resulted in a wide range of evolved host-microbial interdependencies, including those observed in the gut. Ciona intestinalis, a filter-feeding basal chordate and classic developmental model that can be experimentally manipulated, is being employed to help define these relationships. Ciona larvae are first exposed internally to microbes upon the initiation of feeding in metamorphosed individuals; however, whether or not these microbes subsequently colonize the gut and whether or not Ciona forms relationshipsmore » with specific bacteria in the gut remains unknown. Here in this report, we show that the Ciona gut not only is colonized by a complex community of bacteria, but also that samples from three geographically isolated populations reveal striking similarity in abundant operational taxonomic units (OTUs) consistent with the selection of a core community by the gut ecosystem.« less

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.

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

Chicken IL-17F: Identification and comparative expression analysis in Eimeria-Infected chickens

USDA-ARS?s Scientific Manuscript database

Interleukin-17F (IL-17F), belonging to the IL-17 family, is a proinflammatory cytokine and plays an important role in gut homeostasis. A full-length chicken IL-17F (chIL-17F) cDNA with a 510-bp coding region was first identified from ConA-activated splenic lymphocytes of chickens. The chIL-17F share...

Successful treatment of simulated Clostridium difficile infection in a human gut model by fidaxomicin first line and after vancomycin or metronidazole failure.

PubMed

Chilton, C H; Crowther, G S; Freeman, J; Todhunter, S L; Nicholson, S; Longshaw, C M; Wilcox, M H

2014-02-01

Fidaxomicin reduces the risk of recurrent Clostridium difficile infection (CDI) compared with vancomycin. We investigated fidaxomicin primary or secondary treatment efficacy using a gut model. Four triple-stage chemostat gut models were inoculated with faeces. After clindamycin induction of CDI, fidaxomicin (200 mg/L twice daily), vancomycin (125 mg/L four times daily) or metronidazole (9.3 mg/L three times daily) was administered for 7 days. Following failure/CDI recurrence, fidaxomicin (200 mg/L twice daily, 7 days) was instilled. C. difficile (CD) total viable counts (TVC), spore counts (SP), toxin titres (CYT), gut bacteria counts and antimicrobial concentrations were measured throughout. Fidaxomicin instillation reduced CD TVC/SP and CYT below the limit of detection (LOD) after 2 and 4 days, respectively, with no CDI recurrence. Metronidazole instillation failed to decrease CD TVC or CYT. Vancomycin instillation reduced CD TVC and CYT to LOD by day 4, but SP persisted. Recurrence occurred 13 days after vancomycin instillation; subsequent fidaxomicin instillation reduced CD TVC/SP/CYT below the LOD from day 2. CD was isolated sporadically, with no evidence of spore recrudescence or toxin production. Fidaxomicin had a minimal effect on the microflora, except for bifidobacteria. Fidaxomicin was detected for at least 21 days post-instillation, whereas other antimicrobials were undetectable beyond ∼4 days. Fidaxomicin successfully treated simulated primary and recurrent CDI. Fidaxomicin was superior to metronidazole in reducing CD TVC and SP, and superior to vancomycin in reducing SP without recurrence of vegetative cell growth. Fidaxomicin, but not vancomycin or metronidazole, persisted in the gut model for >20 days after instillation.

Genomic and metabolic studies of the impact of probiotics on a model gut symbiont and host.

PubMed

Sonnenburg, Justin L; Chen, Christina T L; Gordon, Jeffrey I

2006-11-01

Probiotics are deliberately ingested preparations of live bacterial species that confer health benefits on the host. Many of these species are associated with the fermentation of dairy products. Despite their increasing use, the molecular details of the impact of various probiotic preparations on resident members of the gut microbiota and the host are generally lacking. To address this issue, we colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the adult human gut microbiota, and Bifidobacterium longum, a minor member but a commonly used probiotic. Simultaneous whole genome transcriptional profiling of both bacterial species in their gut habitat and of the intestinal epithelium, combined with mass-spectrometric analysis of habitat-associated carbohydrates, revealed that the presence of B. longum elicits an expansion in the diversity of polysaccharides targeted for degradation by B. thetaiotaomicron (e.g., mannose- and xylose-containing glycans), and induces host genes involved in innate immunity. Although the overall transcriptome expressed by B. thetaiotaomicron when it encounters B. longum in the cecum is dependent upon the genetic background of the mouse (as assessed by a mixed analysis of variance [ANOVA] model of co-colonization experiments performed in NMRI and C57BL/6J animals), B. thetaiotaomicron's expanded capacity to utilize polysaccharides occurs independently of host genotype, and is also observed with a fermented dairy product-associated strain, Lactobacillus casei. This gnotobiotic mouse model provides a controlled case study of how a resident symbiont and a probiotic species adapt their substrate utilization in response to one another, and illustrates both the generality and specificity of the relationship between a host, a component of its microbiota, and intentionally consumed microbial species.

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota.

PubMed

Xu, Jun; Chen, Hu-Biao; Li, Song-Lin

2017-09-01

Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota-metabolized HMs, direct microbial analysis of HM-targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM-based drug discovery. © 2016 Wiley Periodicals, Inc.

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

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.

Variable responses of human and non-human primate gut microbiomes to a Western diet.

PubMed

Amato, Katherine R; Yeoman, Carl J; Cerda, Gabriela; Schmitt, Christopher A; Cramer, Jennifer Danzy; Miller, Margret E Berg; Gomez, Andres; Turner, Trudy R; Wilson, Brenda A; Stumpf, Rebecca M; Nelson, Karen E; White, Bryan A; Knight, Rob; Leigh, Steven R

2015-11-16

The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.

F-theory and AdS3/CFT2 (2, 0)

NASA Astrophysics Data System (ADS)

Couzens, Christopher; Martelli, Dario; Schäfer-Nameki, Sakura

2018-06-01

We continue to develop the program initiated in [1] of studying supersymmetric AdS3 backgrounds of F-theory and their holographic dual 2d superconformal field theories, which are dimensional reductions of theories with varying coupling. Imposing 2d N=(0,2) supersymmetry,wederivethegeneralconditionsonthegeometryforTypeIIB AdS3 solutions with varying axio-dilaton and five-form flux. Locally the compact part of spacetime takes the form of a circle fibration over an eight-fold Y_8^{τ } , which is elliptically fibered over a base \\tilde{M}_6 . We construct two classes of solutions given in terms of a product ansatz \\tilde{M}_6}=Σ × {M}_4 , where Σ is a complex curve and \\tilde{M}_4 is locally a Kähler surface. In the first class \\tilde{M}_4 is globally a Kähler surface and we take the elliptic fibration to vary non-trivially over either of these two factors, where in both cases the metrics on the total space of the elliptic fibrations are not Ricci-flat. In the second class the metric on the total space of the elliptic fibration over either curve or surface are Ricci-flat. This results in solutions of the type AdS3 × K3 × ℳ 5 τ , dual to 2d (0, 2) SCFTs, and AdS3 × S 3/Γ × CY 3, dual to 2d (0, 4) SCFTs, respectively. In all cases we compute the charges for the dual field theories with varying coupling and find agreement with the holographic results. We also show that solutions with enhanced 2d N=(2,2) supersymmetry must have constant axio-dilaton. Allowing the internal geometry to be non-compact leads to the most general class of Type IIB AdS5 solutions with varying axio-dilaton, i.e. F-theoretic solutions, that are dual to 4d N=1 SCFTs.

2d affine XY-spin model/4d gauge theory duality and deconfinement

NASA Astrophysics Data System (ADS)

Anber, Mohamed M.; Poppitz, Erich; Ünsal, Mithat

2012-04-01

We introduce a duality between two-dimensional XY-spin models with symmetry-breaking perturbations and certain four-dimensional SU(2) and SU(2)/ {{Z}_2} gauge theories, compactified on a small spatial circle {{R}^{{^{{{1},{2}}}}}} × {{S}^{{^{{1}}}}} , and considered at temperatures near the deconfinement transition. In a Euclidean set up, the theory is defined on {{R}^{{^{{2}}}}} × {{T}^{{^{{2}}}}} . Similarly, thermal gauge theories of higher rank are dual to new families of "affine" XY-spin models with perturbations. For rank two, these are related to models used to describe the melting of a 2d crystal with a triangular lattice. The connection is made through a multi-component electric-magnetic Coulomb gas representation for both systems. Perturbations in the spin system map to topological defects in the gauge theory, such as monopole-instantons or magnetic bions, and the vortices in the spin system map to the electrically charged W-bosons in field theory (or vice versa, depending on the duality frame). The duality permits one to use the two-dimensional technology of spin systems to study the thermal deconfinement and discrete chiral transitions in four-dimensional SU( N c ) gauge theories with n f ≥1 adjoint Weyl fermions.

The gut eukaryotic microbiota influences the growth performance among cohabitating shrimp.

PubMed

Dai, Wenfang; Yu, Weina; Zhang, Jinjie; Zhu, Jinyong; Tao, Zhen; Xiong, Jinbo

2017-08-01

Increasing evidence has revealed a close interplay between the gut bacterial communities and host growth performance. However, until recently, studies generally ignored the contribution of eukaryotes, endobiotic organisms. To fill this gap, we used Illumina sequencing technology on eukaryotic 18S rRNA gene to compare the structures of gut eukaryotic communities among cohabitating retarded, overgrown, and normal shrimp obtained from identically managed ponds. Results showed that a significant difference between gut eukaryotic communities differed significantly between water and intestine and among three shrimp categories. Structural equation modeling revealed that changes in the gut eukaryotic community were positively related to digestive enzyme activities, which in turn influenced shrimp growth performance (λ = 0.97, P < 0.001). Overgrown shrimp exhibited a more complex and cooperative gut eukaryotic interspecies interaction than retarded and normal shrimp, which may facilitate their nutrient acquisition efficiency. Notably, the distribution of dominant eukaryotic genera and shifts in keystone species were closely concordant with shrimp growth performance. In summary, this study provides an integrated overview on direct roles of gut eukaryotic communities in shrimp growth performance instead of well-studied bacterial assembly.

Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota.

PubMed

Bird, Julia K; Raederstorff, Daniel; Weber, Peter; Steinert, Robert E

2017-11-01

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine N -oxide concentrations. Modulating the composition of the gut microbiota by resveratrol may affect central energy metabolism and modify concentrations of satiety hormones to produce antiobesity effects. Encouraging research from animal models could be tested in humans. © 2017 American Society for Nutrition.

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.

From anomalies of finite symmetries to heterotic GUTs

NASA Astrophysics Data System (ADS)

Vaudrevange, Patrick K. S.

2017-11-01

We review the role of finite symmetries for particle physics with special emphasis on discrete anomalies and on their possible origin from extra dimensions. Then, we apply our knowledge on finite symmetries to the problematic proton decay operators of various mass-dimensions, focusing on ℤ4R , i.e. a special R-symmetry of order 4. We show that this ℤ4R symmetry can naturally originate from extra dimensions as a discrete remnant of higher-dimensional Lorentz symmetry. Finally, in order to obtain a unified picture from the heterotic string theory we discuss grand unified theories (GUTs) in extra dimensions compactified on ℤ2 × ℤ2 orbifolds and show how proton decay operators can be suppressed in a certain class of orbifolds.

Role of the gut microbiota in host appetite control: bacterial growth to animal feeding behaviour.

PubMed

Fetissov, Sergueï O

2017-01-01

The life of all animals is dominated by alternating feelings of hunger and satiety - the main involuntary motivations for feeding-related behaviour. Gut bacteria depend fully on their host for providing the nutrients necessary for their growth. The intrinsic ability of bacteria to regulate their growth and to maintain their population within the gut suggests that gut bacteria can interfere with molecular pathways controlling energy balance in the host. The current model of appetite control is based mainly on gut-brain signalling and the animal's own needs to maintain energy homeostasis; an alternative model might also involve bacteria-host communications. Several bacterial components and metabolites have been shown to stimulate intestinal satiety pathways; at the same time, their production depends on bacterial growth cycles. This short-term bacterial growth-linked modulation of intestinal satiety can be coupled with long-term regulation of appetite, controlled by the neuropeptidergic circuitry in the hypothalamus. Indeed, several bacterial products are detected in the systemic circulation, which might act directly on hypothalamic neurons. This Review analyses the data relevant to possible involvement of the gut bacteria in the regulation of host appetite and proposes an integrative homeostatic model of appetite control that includes energy needs of both the host and its gut bacteria.

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.

Microfluidic Gut-liver chip for reproducing the first pass metabolism.

PubMed

Choe, Aerim; Ha, Sang Keun; Choi, Inwook; Choi, Nakwon; Sung, Jong Hwan

2017-03-01

After oral intake of drugs, drugs go through the first pass metabolism in the gut and the liver, which greatly affects the final outcome of the drugs' efficacy and side effects. The first pass metabolism is a complex process involving the gut and the liver tissue, with transport and reaction occurring simultaneously at various locations, which makes it difficult to be reproduced in vitro with conventional cell culture systems. In an effort to tackle this challenge, here we have developed a microfluidic gut-liver chip that can reproduce the dynamics of the first pass metabolism. The microfluidic chip consists of two separate layers for gut epithelial cells (Caco-2) and the liver cells (HepG2), and is designed so that drugs go through a sequential absorption in the gut chamber and metabolic reaction in the liver chamber. We fabricated the chip and showed that the two different cell lines can be successfully co-cultured on chip. When the two cells are cultured on chip, changes in the physiological function of Caco-2 and HepG2 cells were noted. The cytochrome P450 metabolic activity of both cells were significantly enhanced, and the absorptive property of Caco-2 cells on chip also changed in response to the presence of flow. Finally, first pass metabolism of a flavonoid, apigenin, was evaluated as a model compound, and co-culture of gut and liver cells on chip resulted in a metabolic profile that is closer to the reported profile than a monoculture of gut cells. This microfluidic gut-liver chip can potentially be a useful platform to study the complex first pass metabolism of drugs in vitro.

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.

F-theory models on K3 surfaces with various Mordell-Weil ranks — constructions that use quadratic base change of rational elliptic surfaces

NASA Astrophysics Data System (ADS)

Kimura, Yusuke

2018-05-01

We constructed several families of elliptic K3 surfaces with Mordell-Weil groups of ranks from 1 to 4. We studied F-theory compactifications on these elliptic K3 surfaces times a K3 surface. Gluing pairs of identical rational elliptic surfaces with nonzero Mordell-Weil ranks yields elliptic K3 surfaces, the Mordell-Weil groups of which have nonzero ranks. The sum of the ranks of the singularity type and the Mordell-Weil group of any rational elliptic surface with a global section is 8. By utilizing this property, families of rational elliptic surfaces with various nonzero Mordell-Weil ranks can be obtained by choosing appropriate singularity types. Gluing pairs of these rational elliptic surfaces yields families of elliptic K3 surfaces with various nonzero Mordell-Weil ranks. We also determined the global structures of the gauge groups that arise in F-theory compactifications on the resulting K3 surfaces times a K3 surface. U(1) gauge fields arise in these compactifications.

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

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.

GLP-1 nanomedicine alleviates gut inflammation

PubMed Central

Anbazhagan, Arivarasu N.; Thaqi, Mentor; Priyamvada, Shubha; Jayawardena, Dulari; Kumar, Anoop; Gujral, Tarunmeet; Chatterjee, Ishita; Mugarza, Edurne; Saksena, Seema; Onyuksel, Hayat; Dudeja, Pradeep K.

2017-01-01

The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate thatGLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD). PMID:27553076

Inflammatory Bowel Disease Therapies and Gut Function in a Colitis Mouse Model

PubMed Central

Nahidi, Lily; Leach, Steven T.; Mitchell, Hazel M.; Kaakoush, Nadeem O.; Lemberg, Daniel A.; Munday, John S.; Huinao, Karina; Day, Andrew S.

2013-01-01

Background. Exclusive enteral nutrition (EEN) is a well-established approach to the management of Crohn's disease. Aim. To determine effects of EEN upon inflammation and gut barrier function in a colitis mouse model. Methods. Interleukin-10-deficient mice (IL-10−/−) were inoculated with Helicobacter trogontum and then treated with EEN, metronidazole, hydrocortisone, or EEN and metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with histology, mucosal integrity, tight junction integrity, inflammation, and H. trogontum load evaluated. Results. H. trogontum induced colitis in IL-10−/− mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA in infected mice was associated with intestinal barrier dysfunction indicated by decreased transepithelial electrical resistance and mRNA of tight junction proteins and increased short-circuit current, myosin light chain kinase mRNA, paracellular permeability, and tumor necrosis factor-α and myeloperoxidase plasma levels (P < 0.01 for all comparisons). EEN and metronidazole, but not hydrocortisone, treatments restored barrier function, maintained gut barrier integrity, and reversed inflammatory changes along with reduction of H. trogontum load (versus infected controls P < 0.05). Conclusion. H. trogontum infection in IL-10−/− mice induced typhlocolitis with intestinal barrier dysfunction. EEN and metronidazole, but not hydrocortisone, modulate barrier dysfunction and reversal of inflammatory changes. PMID:24027765

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.

On Growth and Form of the Zebrafish Gut Microbiome

NASA Astrophysics Data System (ADS)

Jemielita, Matthew; Taormina, Michael; Rolig, Annah; Burns, Adam; Hampton, Jennifer; Guillemin, Karen; Parthasarathy, Raghuveer

2014-03-01

The vertebrate gut is home to a diverse microbial community whose composition has a strong influence on the development and health of the host organism. Researchers can identify the members of the microbiota, yet little is known about the spatial and temporal dynamics of these microbial communities, including the mechanisms guiding their nucleation, growth, and interactions. We address these issues using the larval zebrafish (Danio rerio) as a model organism, which are raised microbe-free and then inoculated with controlled compositions of fluorophore-expressing bacteria. Live imaging using light sheet fluorescence microscopy enables visualization of the gut's entire microbial population over the first 24 hours of colonization. Image analysis allows us to quantify microbial populations that range from a few individuals to tens of thousands of microbes, and analyze the structure and growth kinetics of gut bacterial communities. We find that genetically-identical microbes can show surprisingly different growth rates and colonization abilities depending on their order of arrival. This demonstrates that knowing only the constituents of the gut community is insufficient to determine their dynamics; rather, the history of colonization matters.

[Diet and gut microbiota: two sides of the same coin?

PubMed

Schiumerini, Ramona; Pasqui, Francesca; Festi, Davide

2018-01-01

Gut microbiota is a complex ecosystem, resident in the digestive tract, exerting multiple functions that can have a significant impact on the pathophysiology of the host organism. The composition and functions of this "superorganism" are influenced by many factors, and among them, the host's dietary habits seem to have a significant effect. Dietary changes in the evolution of human history and in the different stages of life of the human subjects are responsible for qualitative and functional modification of gut microbiota. At the same time, the different dietary models adopted in worldwide geographic areas take into account the inter-individual differences concerning composition and microbial function. This close relationship between diet, gut microbiota and host seems, in fact, to be responsible for the protection or predisposition to develop several metabolic, immunological, neoplastic and functional diseases. Thus, several studies have evaluated the impact of diet and lifestyle modification strategies on gut microbiota composition and functions which, in turn, seems to affect the effectiveness of such therapeutic measures. Gut microbiota manipulation strategies, as complementary to dietary modifications, represent a fascinating field of research, even if consolidated data are still lacking.

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

Rapid Change of Microbiota Diversity in the Gut but Not the Hepatopancreas During Gonadal Development of the New Shrimp Model Neocaridina denticulata.

PubMed

Cheung, Man Kit; Yip, Ho Yin; Nong, Wenyan; Law, Patrick Tik Wan; Chu, Ka Hou; Kwan, Hoi Shan; Hui, Jerome Ho Lam

2015-12-01

During evolution of animals, their co-evolution with bacteria has generally been ignored. Recent studies have provided evidences that the symbiotic bacteria in the animal gut can either be essential or contributing to the plasticity of the host. The Crustacea includes crab, crayfish, lobster, and shrimp and represents the second largest subphylum on the planet. Although there are already studies investigating the intestinal bacterial communities in crustaceans, none of them has examined the microbiota in different parts of the digestive system during the gonad development of the host. Here, we utilized a new shrimp model Neocaridina denticulata and sequenced the 16S rRNA using the Ion Torrent platform to survey the bacterial populations colonizing the hepatopancreas, foregut, and intestine, including midgut and hindgut, of the early, mid, and late ovarian maturation stages of the shrimp. The predominant bacteria phylum was found to be Proteobacteria, with more than 80 % reads from the gut flora at the early gonad development belonged to a Coxiella-type bacterium. Distinct bacterial communities can be detected between the hepatopancreas and gut, although no significant difference could be revealed between the different regions of the gut investigated. Surprisingly, during the gonad development, bacterial diversity changed rapidly in the gut but not the hepatopancreas. This study provides the first evidence that microbiota modified differentially in specific regions of the digestive tract during gonadal development of crustaceans.

Structural changes of gut microbiota in a rat non-alcoholic fatty liver disease model treated with a Chinese herbal formula.

PubMed

Yin, Xiaochen; Peng, Jinghua; Zhao, Liping; Yu, Yunpeng; Zhang, Xu; Liu, Ping; Feng, Qin; Hu, Yiyang; Pang, Xiaoyan

2013-05-01

Accumulating evidence indicates that disruption of the gut microbiota by a high-fat diet (HFD) may play a pivotal role in the progression of metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). In this study, the structural changes of gut microbiota were analyzed in an HFD-induced NAFLD rat model during treatment with an ancient Chinese herbal formula (CHF) used in clinical practice -Qushi Huayu Fang. CHF treatment significantly reduced body weight, alleviated hepatic steatosis, and decreased the content of triglycerides and free fatty acids in the livers of the rats. Gut microbiota of treated and control rats were profiled with polymerase chain reaction-denaturing gradient gel electrophoresis and bar-coded pyrosequencing of the V3 region of 16S rRNA genes. Both analyses indicated that the CHF-treated group harbored significantly different gut microbiota from that of model rats. Partial least squares discriminant analysis and taxonomy-based analysis were further employed to identify key phylotypes responding to HFD and CHF treatment. Most notably, the genera Escherichia/Shigella, containing opportunistic pathogens, were significantly enriched in HFD-fed rats compared to controls fed normal chow (P<0.05) but they decreased to control levels after CHF treatment. Collinsella, a genus with short chain fatty acid producers, was significantly elevated in CHF-treated rats compared to HFD-fed rats (P<0.05). The results revealed that the bacterial profiles of HFD-induced rats could be modulated by the CHF. Elucidation of these differences in microbiota composition provided a basis for further understanding the pharmacological mechanism of the CHF. Copyright © 2013 Elsevier GmbH. All rights reserved.

Surveying the SO(10) model landscape: The left-right symmetric case

NASA Astrophysics Data System (ADS)

Deppisch, Frank F.; Gonzalo, Tomás E.; Graf, Lukas

2017-09-01

Grand unified theories (GUTs) are a very well motivated extensions of the Standard Model (SM), but the landscape of models and possibilities is overwhelming, and different patterns can lead to rather distinct phenomenologies. In this work we present a way to automatize the model building process, by considering a top to bottom approach that constructs viable and sensible theories from a small and controllable set of inputs at the high scale. By providing a GUT scale symmetry group and the field content, possible symmetry breaking paths are generated and checked for consistency, ensuring anomaly cancellation, SM embedding and gauge coupling unification. We emphasize the usefulness of this approach for the particular case of a nonsupersymmetric SO(10) model with an intermediate left-right symmetry, and we analyze how low-energy observables such as proton decay and lepton flavor violation might affect the generated model landscape.

Influence of the Enteric Nervous System on Gut Motility Patterns in Zebrafish

NASA Astrophysics Data System (ADS)

Baker, Ryan; Ganz, Julia; Melancon, Ellie; Eisen, Judith; Parthasarathy, Raghuveer

The enteric nervous system (ENS), composed of diverse neuronal subtypes and glia, regulates essential gut functions including motility, secretion, and homeostasis. In humans and animals, decreased numbers of enteric neurons lead to a variety of types of gut dysfunction. However, surprisingly little is known about how the number, position, or subtype of enteric neurons affect the regulation of gut peristalsis, due to the lack of good model systems and the lack of tools for the quantitative characterization of gut motion. We have therefore developed a method of quantitative spatiotemporal mapping using differential interference contrast microscopy and particle image velocimetry, and have applied this to investigate intestinal dynamics in normal and mutant larval zebrafish. From movies of gut motility, we obtain a velocity vector field representative of gut motion, from which we can quantify parameters relating to gut peristalsis such as frequency, wave speed, deformation amplitudes, wave duration, and non-linearity of waves. We show that mutants with reduced neuron number have contractions that are more regular in time and reduced in amplitude compared to wild-type (normal) fish. We also show that feeding fish before their yolk is consumed leads to stronger motility patterns. We acknowledge support from NIH awards P50 GM098911 and P01 HD022486.

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.

Altered brain-gut axis in autism: comorbidity or causative mechanisms?

PubMed

Mayer, Emeran A; Padua, David; Tillisch, Kirsten

2014-10-01

The concept that alterated communications between the gut microbiome and the brain may play an important role in human brain disorders has recently received considerable attention. This is the result of provocative preclinical and some clinical evidence supporting early hypotheses about such communication in health and disease. Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. In addition, alteration in the composition and metabolic products of the gut microbiome has long been implicated as a possible causative mechanism contributing to ASD pathophysiology, and this hypothesis has been supported by several recently published evidence from rodent models of autism induced by prenatal insults to the mother. Recent evidence in one such model involving maternal infection, that is characterized by alterations in behavior, gut physiology, microbial composition, and related metabolite profile, suggests a possible benefit of probiotic treatment on several of the observed abnormal behaviors. © 2014 WILEY Periodicals, Inc.

Human Gut-Derived Commensal Bacteria Suppress CNS Inflammatory and Demyelinating Disease.

PubMed

Mangalam, Ashutosh; Shahi, Shailesh K; Luckey, David; Karau, Melissa; Marietta, Eric; Luo, Ningling; Choung, Rok Seon; Ju, Josephine; Sompallae, Ramakrishna; Gibson-Corley, Katherine; Patel, Robin; Rodriguez, Moses; David, Chella; Taneja, Veena; Murray, Joseph

2017-08-08

The human gut is colonized by a large number of microorganisms (∼10 13 bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune responses. P. histicola challenge led to a decrease in pro-inflammatory Th1 and Th17 cells and an increase in the frequencies of CD4 + FoxP3 + regulatory T cells, tolerogenic dendritic cells, and suppressive macrophages. Our study provides evidence that the administration of gut commensals may regulate a systemic immune response and may, therefore, have a possible role in treatment strategies for MS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Beneficial effects of Rifaximin in post-infectious irritable bowel syndrome mouse model beyond gut microbiota.

PubMed

Jin, Yu; Ren, Xiaoyang; Li, Gangping; Li, Ying; Zhang, Lei; Wang, Huan; Qian, Wei; Hou, Xiaohua

2018-02-01

Rifaximin is a minimally absorbed antibiotic, which has shown efficacy in irritable bowel syndrome (IBS) patients. However, the mechanism on how it effects in IBS is still incompletely defined. In this study, Trichinella spiralis-infected post-infectious (PI) IBS mouse model was used, to assess the action of rifaximin on visceral hypersensitivity, barrier function, gut inflammation, and microbiota. Post-infectious IBS model was established by T. spiralis infection in mice. Rifaximin were administered to PI-IBS mice for seven consecutive days. The abdominal withdrawal reflex and threshold of colorectal distention were employed to evaluate visceral sensitivity. Smooth muscle contractile response was recorded in the organ bath. Intestinal permeability was measured by Ussing chamber. Expression of tight junction protein and cytokines were measured by Western blotting. Ilumina miseq platform was used to analyze bacterial 16S ribosomal RNA. Post-infectious IBS mice treated with rifaximin exhibited decreased abdominal withdrawal reflex score, increased threshold, reduced contractile response, and intestinal permeability. Rifaximin also suppressed the expression of interleukin-12 and interleukin-17 and promoted the expression of the major tight junction protein occludin. Furthermore, rifaximin did not change the composition and diversity, and the study reavealed that rifaximin had a tiny effect on the relative abundance of Lactobacillus and Bifidobacterium in this PI-IBS model. Rifaximin alleviated visceral hypersensitivity, recovered intestinal barrier function, and inhibited low-grade inflammation in colon and ileum of PI-IBS mouse model. Moreover, rifaximin exerts anti-inflammatory effects with only a minimal effect on the overall composition and diversity of the gut microbiota in this model. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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

Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.

PubMed

Cignarella, Francesca; Cantoni, Claudia; Ghezzi, Laura; Salter, Amber; Dorsett, Yair; Chen, Lei; Phillips, Daniel; Weinstock, George M; Fontana, Luigi; Cross, Anne H; Zhou, Yanjiao; Piccio, Laura

2018-06-05

Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome. Copyright © 2018 Elsevier Inc. All rights reserved.

Formation of gut-like structures in vitro from mouse embryonic stem cells.

PubMed

Torihashi, Shigeko

2006-01-01

Embryonic stem (ES) cells have the potential to differentiate into all cell types originating from the three germ layers; however, there are still few reports about the formation of functional organs from embryonic stem cells. Recently, we reported that by hanging drops of mouse ES cells, embryoid bodies (EBs) formed gut-like structures in vitro composed of three layers corresponding to the epithelium, lamina propria, and musculature. The morphological features and the process of formation are similar to gut and its organogenesis in vivo. Thus, this is a good model for development of the gut and a useful tool for analysis of the factors required for gut organogenesis. The protocol basically involves a method of hanging drops to make EBs, which are then plated on coated dishes for outgrowth. EBs develop to form gut-like structures when induced to spontaneously enter a program of differentiation in vitro without addition of any extrinsic factors.

Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives

PubMed Central

Lang, Yue

2018-01-01

The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS. PMID:29805314

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.

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.

Realising effective theories of tribrid inflation: are there effects from messenger fields?

NASA Astrophysics Data System (ADS)

Antusch, Stefan; Nolde, David

2015-09-01

Tribrid inflation is a variant of supersymmetric hybrid inflation in which the inflaton is a matter field (which can be charged under gauge symmetries) and inflation ends by a GUT-scale phase transition of a waterfall field. These features make tribrid inflation a promising framework for realising inflation with particularly close connections to particle physics. Superpotentials of tribrid inflation involve effective operators suppressed by some cutoff scale, which is often taken as the Planck scale. However, these operators may also be generated by integrating out messenger superfields with masses below the Planck scale, which is in fact quite common in GUT and/or flavour models. The values of the inflaton field during inflation can then lie above this mass scale, which means that for reliably calculating the model predictions one has to go beyond the effective theory description. We therefore discuss realisations of effective theories of tribrid inflation and specify in which cases effects from the messenger fields are expected, and under which conditions they can safely be neglected. In particular, we point out how to construct realisations where, despite the fact that the inflaton field values are above the messenger mass scale, the predictions for the observables are (to a good approximation) identical to the ones calculated in the effective theory treatment where the messenger mass scale is identified with the (apparent) cutoff scale.

3D gut-liver chip with a PK model for prediction of first-pass metabolism.

PubMed

Lee, Dong Wook; Ha, Sang Keun; Choi, Inwook; Sung, Jong Hwan

2017-11-07

Accurate prediction of first-pass metabolism is essential for improving the time and cost efficiency of drug development process. Here, we have developed a microfluidic gut-liver co-culture chip that aims to reproduce the first-pass metabolism of oral drugs. This chip consists of two separate layers for gut (Caco-2) and liver (HepG2) cell lines, where cells can be co-cultured in both 2D and 3D forms. Both cell lines were maintained well in the chip, verified by confocal microscopy and measurement of hepatic enzyme activity. We investigated the PK profile of paracetamol in the chip, and corresponding PK model was constructed, which was used to predict PK profiles for different chip design parameters. Simulation results implied that a larger absorption surface area and a higher metabolic capacity are required to reproduce the in vivo PK profile of paracetamol more accurately. Our study suggests the possibility of reproducing the human PK profile on a chip, contributing to accurate prediction of pharmacological effect of drugs.

Impact of passive permeability and gut efflux transport on the oral bioavailability of novel series of piperidine-based renin inhibitors in rodents.

PubMed

Lévesque, Jean-François; Bleasby, Kelly; Chefson, Amandine; Chen, Austin; Dubé, Daniel; Ducharme, Yves; Fournier, Pierre-André; Gagné, Sébastien; Gallant, Michel; Grimm, Erich; Hafey, Michael; Han, Yongxin; Houle, Robert; Lacombe, Patrick; Laliberté, Sébastien; MacDonald, Dwight; Mackay, Bruce; Papp, Robert; Tschirret-Guth, Richard

2011-09-15

An oral bioavailability issue encountered during the course of lead optimization in the renin program is described herein. The low F(po) of pyridone analogs was shown to be caused by a combination of poor passive permeability and gut efflux transport. Substitution of pyridone ring for a more lipophilic moiety (logD>1.7) had minimal effect on rMdr1a transport but led to increased passive permeability (P(app)>10 × 10(-6) cm/s), which contributed to overwhelm gut transporters and increase rat F(po). LogD and in vitro passive permeability determination were found to be key in guiding SAR and improve oral exposure of renin inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Modeling polymer-induced interactions between two grafted surfaces: comparison between interfacial statistical associating fluid theory and self-consistent field theory.

PubMed

Jain, Shekhar; Ginzburg, Valeriy V; Jog, Prasanna; Weinhold, Jeffrey; Srivastava, Rakesh; Chapman, Walter G

2009-07-28

The interaction between two polymer grafted surfaces is important in many applications, such as nanocomposites, colloid stabilization, and polymer alloys. In our previous work [Jain et al., J. Chem. Phys. 128, 154910 (2008)], we showed that interfacial statistical associating fluid density theory (iSAFT) successfully calculates the structure of grafted polymer chains in the absence/presence of a free polymer. In the current work, we have applied this density functional theory to calculate the force of interaction between two such grafted monolayers in implicit good solvent conditions. In particular, we have considered the case where the segment sizes of the free (sigma(f)) and grafted (sigma(g)) polymers are different. The interactions between the two monolayers in the absence of the free polymer are always repulsive. However, in the presence of the free polymer, the force either can be purely repulsive or can have an attractive minimum depending upon the relative chain lengths of the free (N(f)) and grafted polymers (N(g)). The attractive minimum is observed only when the ratio alpha = N(f)/N(g) is greater than a critical value. We find that these critical values of alpha satisfy the following scaling relation: rho(g) square root(N(g)) beta(3) proportional to alpha(-lambda), where beta = sigma(f)/sigma(g) and lambda is the scaling exponent. For beta = 1 or the same segment sizes of the free and grafted polymers, this scaling relation is in agreement with those from previous theoretical studies using self-consistent field theory (SCFT). Detailed comparisons between iSAFT and SCFT are made for the structures of the monolayers and their forces of interaction. These comparisons lead to interesting implications for the modeling of nanocomposite thermodynamics.

Human symbionts inject and neutralize antibacterial toxins to persist in the gut.

PubMed

Wexler, Aaron G; Bao, Yiqiao; Whitney, John C; Bobay, Louis-Marie; Xavier, Joao B; Schofield, Whitman B; Barry, Natasha A; Russell, Alistair B; Tran, Bao Q; Goo, Young Ah; Goodlett, David R; Ochman, Howard; Mougous, Joseph D; Goodman, Andrew L

2016-03-29

The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes--one of two major phyla in the gut--also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation.

Antibiotic exposure perturbs the gut microbiota and elevates mortality in honeybees

PubMed Central

Shaffer, Zack; Moran, Nancy A.

2017-01-01

Gut microbiomes play crucial roles in animal health, and shifts in the gut microbial community structure can have detrimental impacts on hosts. Studies with vertebrate models and human subjects suggest that antibiotic treatments greatly perturb the native gut community, thereby facilitating proliferation of pathogens. In fact, persistent infections following antibiotic treatment are a major medical issue. In apiculture, antibiotics are frequently used to prevent bacterial infections of larval bees, but the impact of antibiotic-induced dysbiosis (microbial imbalance) on bee health and susceptibility to disease has not been fully elucidated. Here, we evaluated the effects of antibiotic exposure on the size and composition of honeybee gut communities. We monitored the survivorship of bees following antibiotic treatment in order to determine if dysbiosis of the gut microbiome impacts honeybee health, and we performed experiments to determine whether antibiotic exposure increases susceptibility to infection by opportunistic pathogens. Our results show that antibiotic treatment can have persistent effects on both the size and composition of the honeybee gut microbiome. Antibiotic exposure resulted in decreased survivorship, both in the hive and in laboratory experiments in which bees were exposed to opportunistic bacterial pathogens. Together, these results suggest that dysbiosis resulting from antibiotic exposure affects bee health, in part due to increased susceptibility to ubiquitous opportunistic pathogens. Not only do our results highlight the importance of the gut microbiome in honeybee health, but they also provide insights into how antibiotic treatment affects microbial communities and host health. PMID:28291793

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

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

On the development of a model predicting the recrystallization texture of aluminum using the Taylor model for rolling textures and the coincidence lattice site theory

NASA Astrophysics Data System (ADS)

T, Morimoto; F, Yoshida; A, Yanagida; J, Yanagimoto

2015-04-01

First, hardening model in f.c.c. metals was formulated with collinear interactions slips, Hirth slips and Lomer-Cottrell slips. Using the Taylor and the Sachs rolling texture prediction model, the residual dislocation densities of cold-rolled commercial pure aluminum were estimated. Then, coincidence site lattice grains were investigated from observed cold rolling texture. Finally, on the basis of oriented nucleation theory and coincidence site lattice theory, the recrystallization texture of commercial pure aluminum after low-temperature annealing was predicted.

Complex pectin metabolism by gut bacteria reveals novel catalytic functions

PubMed Central

Baslé, Arnaud; Gray, Joseph; Venditto, Immacolata; Briggs, Jonathon; Zhang, Xiaoyang; Labourel, Aurore; Terrapon, Nicolas; Buffetto, Fanny; Nepogodiev, Sergey; Xiao, Yao; Field, Robert A.; Zhu, Yanping; O’Neil, Malcolm A.; Urbanowicz, Breeana R.; York, William S.; Davies, Gideon J.; Abbott, D. Wade; Ralet, Marie-Christine; Martens, Eric C.; Henrissat, Bernard; Gilbert, Harry J.

2017-01-01

Carbohydrate polymers drive microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron utilizes the most structurally complex glycan known; the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but one of its 21 distinct glycosidic linkages. We show that rhamnogalacturonan-II side-chain and backbone deconstruction are coordinated, to overcome steric constraints, and that degradation reveals previously undiscovered enzyme families and novel catalytic activities. The degradome informs revision of the current structural model of RG-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycans in the human diet. PMID:28329766

Bayesian analysis of non-linear differential equation models with application to a gut microbial ecosystem.

PubMed

Lawson, Daniel J; Holtrop, Grietje; Flint, Harry

2011-07-01

Process models specified by non-linear dynamic differential equations contain many parameters, which often must be inferred from a limited amount of data. We discuss a hierarchical Bayesian approach combining data from multiple related experiments in a meaningful way, which permits more powerful inference than treating each experiment as independent. The approach is illustrated with a simulation study and example data from experiments replicating the aspects of the human gut microbial ecosystem. A predictive model is obtained that contains prediction uncertainty caused by uncertainty in the parameters, and we extend the model to capture situations of interest that cannot easily be studied experimentally. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toward Personalized Control of Human Gut Bacterial Communities.

PubMed

David, Lawrence A

2018-01-01

A key challenge in microbiology will be developing tools for manipulating human gut bacterial communities. Our ability to predict and control the dynamics of these communities is now in its infancy. To manage human gut microbiota, I am developing methods in three research domains. First, I am refining in vitro tools to experimentally study gut microbes at high throughput and in controlled settings. Second, I am adapting "big data" techniques to overcome statistical challenges confronting microbiota modeling. Third, I am testing study designs that can streamline human testing of microbiota manipulations. Assembling these methods creates new challenges, including training scientists who can work across disciplines such as engineering, ecology, and medicine. Nevertheless, I envision that overcoming these obstacles will enable my group to construct platforms that can personalize microbiota treatments, particularly ones based on diet. More broadly, I anticipate that such platforms will have applications across fields such as agriculture, biotechnology, and environmental management.

Density Functional Theory Modeling of Ferrihydrite Nanoparticle Adsorption Behavior

NASA Astrophysics Data System (ADS)

Kubicki, J.

2016-12-01

Ferrihydrite is a critical substrate for adsorption of oxyanion species in the environment1. The nanoparticulate nature of ferrihydrite is inherent to its formation, and hence it has been called a "nano-mineral"2. The nano-scale size and unusual composition of ferrihydrite has made structural determination of this phase problematic. Michel et al.3 have proposed an atomic structure for ferrihydrite, but this model has been controversial4,5. Recent work has shown that the Michel et al.3 model structure may be reasonably accurate despite some deficiencies6-8. An alternative model has been proposed by Manceau9. This work utilizes density functional theory (DFT) calculations to model both the structure of ferrihydrite nanoparticles based on the Michel et al. 3 model as refined in Hiemstra8 and the modified akdalaite model of Manceau9. Adsorption energies of carbonate, phosphate, sulfate, chromate, arsenite and arsenate are calculated. Periodic projector-augmented planewave calculations were performed with the Vienna Ab-initio Simulation Package (VASP10) on an approximately 1.7 nm diameter Michel nanoparticle (Fe38O112H110) and on a 2 nm Manceau nanoparticle (Fe38O95H76). After energy minimization of the surface H and O atoms. The model will be used to assess the possible configurations of adsorbed oxyanions on the model nanoparticles. Brown G.E. Jr. and Calas G. (2012) Geochemical Perspectives, 1, 483-742. Hochella M.F. and Madden A.S. (2005) Elements, 1, 199-203. Michel, F.M., Ehm, L., Antao, S.M., Lee, P.L., Chupas, P.J., Liu, G., Strongin, D.R., Schoonen, M.A.A., Phillips, B.L., and Parise, J.B., 2007, Science, 316, 1726-1729. Rancourt, D.G., and Meunier, J.F., 2008, American Mineralogist, 93, 1412-1417. Manceau, A., 2011, American Mineralogist, 96, 521-533. Maillot, F., Morin, G., Wang, Y., Bonnin, D., Ildefonse, P., Chaneac, C., Calas, G., 2011, Geochimica et Cosmochimica Acta, 75, 2708-2720. Pinney, N., Kubicki, J.D., Middlemiss, D.S., Grey, C.P., and Morgan, D

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.

Intestinal crosstalk: a new paradigm for understanding the gut as the "motor" of critical illness.

PubMed

Clark, Jessica A; Coopersmith, Craig M

2007-10-01

For more than 20 years, the gut has been hypothesized to be the "motor" of multiple organ dysfunction syndrome. As critical care research has evolved, there have been multiple mechanisms by which the gastrointestinal tract has been proposed to drive systemic inflammation. Many of these disparate mechanisms have proved to be important in the origin and propagation of critical illness. However, this has led to an unusual situation where investigators describing the gut as a "motor" revving the systemic inflammatory response syndrome are frequently describing wholly different processes to support their claim (i.e., increased apoptosis, altered tight junctions, translocation, cytokine production, crosstalk with commensal bacteria, etc). The purpose of this review is to present a unifying theory as to how the gut drives critical illness. Although the gastrointestinal tract is frequently described simply as "the gut," it is actually made up of (1) an epithelium; (2) a diverse and robust immune arm, which contains most of the immune cells in the body; and (3) the commensal bacteria, which contain more cells than are present in the entire host organism. We propose that the intestinal epithelium, the intestinal immune system, and the intestine's endogenous bacteria all play vital roles driving multiple organ dysfunction syndrome, and the complex crosstalk between these three interrelated portions of the gastrointestinal tract is what cumulatively makes the gut a "motor" of critical illness.

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.

Cosmological applications of F (T ,TG) gravity

NASA Astrophysics Data System (ADS)

Kofinas, Georgios; Saridakis, Emmanuel N.

2014-10-01

We investigate the cosmological applications of F (T ,TG) gravity, which is a novel modified gravitational theory based on the torsion invariant T and the teleparallel equivalent of the Gauss-Bonnet term TG. F (T ,TG) gravity differs from both F (T ) theories as well as from F (R ,G ) class of curvature modified gravity, and thus its corresponding cosmology proves to be very interesting. In particular, it provides a unified description of the cosmological history from early-times inflation to late-times self-acceleration, without the inclusion of a cosmological constant. Moreover, the dark energy equation-of-state parameter can be quintessence or phantomlike, or experience the phantom-divide crossing, depending on the parameters of the model.

Cosmography of f(R)-brane cosmology

NASA Astrophysics Data System (ADS)

Bouhmadi-López, Mariam; Capozziello, Salvatore; Cardone, Vincenzo F.

2010-11-01

Cosmography is a useful tool to constrain cosmological models, in particular, dark energy models. In the case of modified theories of gravity, where the equations of motion are generally quite complicated, cosmography can contribute to select realistic models without imposing arbitrary choices a priori. Indeed, its reliability is based on the assumptions that the universe is homogeneous and isotropic on large scale and luminosity distance can be “tracked” by the derivative series of the scale factor a(t). We apply this approach to induced gravity brane-world models where an f(R) term is present in the brane effective action. The virtue of the model is to self-accelerate the normal and healthy Dvali-Gabadadze-Porrati branch once the f(R) term deviates from the Hilbert-Einstein action. We show that the model, coming from a fundamental theory, is consistent with the ΛCDM scenario at low redshift. We finally estimate the cosmographic parameters fitting the Union2 Type Ia Supernovae data set and the distance priors from baryon acoustic oscillations and then provide constraints on the present day values of f(R) and its second and third derivatives.

Impact of Omega-3 Fatty Acids on the Gut Microbiota

PubMed Central

Farinon, Barbara

2017-01-01

Long-term dietary habits play a crucial role in creating a host-specific gut microbiota community in humans. Despite the many publications about the effects of carbohydrates (prebiotic fibers), the impact of dietary fats, such as omega-3 polyunsaturated fatty acids (PUFAs), on the gut microbiota is less well defined. The few studies completed in adults showed some common changes in the gut microbiota after omega-3 PUFA supplementation. In particular, a decrease in Faecalibacterium, often associated with an increase in the Bacteroidetes and butyrate-producing bacteria belonging to the Lachnospiraceae family, has been observed. Coincidentally, a dysbiosis of these taxa is found in patients with inflammatory bowel disease. Omega-3 PUFAs can exert a positive action by reverting the microbiota composition in these diseases, and increase the production of anti-inflammatory compounds, like short-chain fatty acids. In addition, accumulating evidence in animal model studies indicates that the interplay between gut microbiota, omega-3 fatty acids, and immunity helps to maintain the intestinal wall integrity and interacts with host immune cells. Finally, human and animal studies have highlighted the ability of omega-3 PUFAs to influence the gut–brain axis, acting through gut microbiota composition. From these findings, the importance of the omega-3 connection to the microbiota emerges, encouraging further studies. PMID:29215589

The impact of Rhodiola rosea on the gut microbial community of Drosophila melanogaster.

PubMed

Labachyan, Khachik E; Kiani, Dara; Sevrioukov, Evgueni A; Schriner, Samuel E; Jafari, Mahtab

2018-01-01

The root extract of Rhodiola rosea has historically been used in Europe and Asia as an adaptogen, and similar to ginseng and Shisandra , shown to display numerous health benefits in humans, such as decreasing fatigue and anxiety while improving mood, memory, and stamina. A similar extract in the Rhodiola family, Rhodiola crenulata , has previously been shown to confer positive effects on the gut homeostasis of the fruit fly, Drosophila melanogaster. Although, R. rosea has been shown to extend lifespan of many organisms such as fruit flies, worms and yeast, its anti-aging mechanism remains uncertain. Using D. melanogaster as our model system, the purpose of this work was to examine whether the anti-aging properties of R. rosea are due to its impact on the microbial composition of the fly gut. Rhodiola rosea treatment significantly increased the abundance of Acetobacter , while subsequently decreasing the abundance of Lactobacillales of the fly gut at 10 and 40 days of age. Additionally, supplementation of the extract decreased the total culturable bacterial load of the fly gut, while increasing the overall quantifiable bacterial load. The extract did not display any antimicrobial activity when disk diffusion tests were performed on bacteria belonging to Microbacterium , Bacillus , and Lactococcus . Under standard and conventional rearing conditions, supplementation of R. rosea significantly alters the microbial community of the fly gut, but without any general antibacterial activity. Further studies should investigate whether R. rosea impacts the gut immunity across multiple animal models and ages.

Dynamic causal modelling on infant fNIRS data: A validation study on a simultaneously recorded fNIRS-fMRI dataset.

PubMed

Bulgarelli, Chiara; Blasi, Anna; Arridge, Simon; Powell, Samuel; de Klerk, Carina C J M; Southgate, Victoria; Brigadoi, Sabrina; Penny, William; Tak, Sungho; Hamilton, Antonia

2018-04-12

Tracking the connectivity of the developing brain from infancy through childhood is an area of increasing research interest, and fNIRS provides an ideal method for studying the infant brain as it is compact, safe and robust to motion. However, data analysis methods for fNIRS are still underdeveloped compared to those available for fMRI. Dynamic causal modelling (DCM) is an advanced connectivity technique developed for fMRI data, that aims to estimate the coupling between brain regions and how this might be modulated by changes in experimental conditions. DCM has recently been applied to adult fNIRS, but not to infants. The present paper provides a proof-of-principle for the application of this method to infant fNIRS data and a demonstration of the robustness of this method using a simultaneously recorded fMRI-fNIRS single case study, thereby allowing the use of this technique in future infant studies. fMRI and fNIRS were simultaneously recorded from a 6-month-old sleeping infant, who was presented with auditory stimuli in a block design. Both fMRI and fNIRS data were preprocessed using SPM, and analysed using a general linear model approach. The main challenges that adapting DCM for fNIRS infant data posed included: (i) the import of the structural image of the participant for spatial pre-processing, (ii) the spatial registration of the optodes on the structural image of the infant, (iii) calculation of an accurate 3-layer segmentation of the structural image, (iv) creation of a high-density mesh as well as (v) the estimation of the NIRS optical sensitivity functions. To assess our results, we compared the values obtained for variational Free Energy (F), Bayesian Model Selection (BMS) and Bayesian Model Average (BMA) with the same set of possible models applied to both the fMRI and fNIRS datasets. We found high correspondence in F, BMS, and BMA between fMRI and fNIRS data, therefore showing for the first time high reliability of DCM applied to infant fNIRS data