Hybrid Localized Spectral Decomposition for multiscale problems

We consider a finite element method for elliptic equation with heterogeneous and possibly high-contrast coefficients based on primal hybrid formulation. A space decomposition as in FETI and BDCC allows a sequential computations of the unknowns through elliptic problems and satisfies equilibrium constraints. One of the resulting problems is non-local but with exponentially decaying solutions, enabling a practical scheme where the basis functions have an extended, but still local, support. We obtain quasi-optimal a priori error estimates for low-contrast problems assuming minimal regularity of the solutions. To also consider the high-contrast case, we propose a variant of our method, enriching the space solution via local eigenvalue problems and obtaining optimal a priori error estimate that mitigates the effect of having coefficients with different magnitudes and again assuming no regularity of the solution. The technique developed is dimensional independent and easy to extend to other problems such as elasticity

A microbial symbiosis factor prevents intestinal inflammatory disease

Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles

The gut microbiota shapes intestinal immune responses during health and disease

Immunological dysregulation is the cause of many non-infectious human diseases such as autoimmunity, allergy and cancer. The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms, both symbiotic and pathogenic. In this Review we discuss findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut. We also highlight the molecular pathways that mediate host–symbiont interactions that regulate proper immune function. Finally, we present recent evidence to support that disturbances in the bacterial microbiota result in dysregulation of adaptive immune cells, and this may underlie disorders such as inflammatory bowel disease. This raises the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms

A microbial symbiosis factor prevents intestinal inflammatory disease

Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles

Coordination of tolerogenic immune responses by the commensal microbiota

All mammals are born ignorant to the existence of micro-organisms. Soon after birth, however, every mammal begins a lifelong association with a multitude of microbes that lay residence on the skin, mouth, vaginal mucosa and gastrointestinal (GI) tract. Approximately 500–1000 different species of microbes have highly evolved to occupy these bodily niches, with the highest density and diversity occurring within the intestine [1]. These organisms play a vital role in mammalian nutrient breakdown and provide resistance to colonization by pathogenic micro-organisms. More recently, however, studies have demonstrated that the microbiota can have a profound and long-lasting effect on the development of our immune system both inside and outside the intestine [2]. While our immune system has evolved to recognize and eradicate foreign entities, it tolerates the symbiotic micro-organisms of the intestine. How and why this tolerance occurs has remained unclear. Here we present evidence that the commensal microbes of the intestine actively induce tolerant responses from the host that coordinate healthy immune responses. Potentially, disruption of this dialogue between the host and microbe can lead to the development of autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), or Type I diabetes (TID). As a wealth of publications have focused on the impact of the microbiota on intestinal immune responses and IBD, this chapter will focus on the extra-intestinal impacts of the microbiota from development to disease and integrate the known mechanisms by which the microbiota is able to actively communicate with its host to promote health

The gut microbiota–brain axis in behaviour and brain disorders

In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health

The gut microbiota–brain axis in behaviour and brain disorders

In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health