Metagenome and metabolism: the tissue microbiota hypothesis

Abstract

Over the last decade, the research community has revealed the role of a new organ: the intestinal microbiota. It is considered as a symbiont that is part of our organism since, at birth, it educates the immune system and contributes to the development of the intestinal vasculature and most probably the nervous system. With the advent of new generation sequencing techniques, a catalogue of genes that belong to this microbiome has been established that lists more than 5 million non-redundant genes called the metagenome. Using germ free mice colonized with the microbiota from different origins, it has been formally demonstrated that the intestinal microbiota causes the onset of metabolic diseases. Further to the role of point mutations in our genome, the microbiota can explain the on-going worldwide pandemic of obesity and diabetes, its dissemination and family inheritance, as well as the diversity of the associated metabolic phenotypes. More recently, the discovery of bacterial DNA within host tissues, such as the liver, the adipose tissue and the blood, which establishes a tissue microbiota, introduces new opportunities to identify targets and predictive biomarkers based on the host to microbiota interaction, as well as to define new strategies for pharmacological, immunomodulatory vaccines and nutritional applications.

Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients

“…In addition to cytokines, MAIT cells could be activated through their TCR by specific ligands generated in the presence of bacterial riboflavin metabolites and methylglyoxal. Changes in the gut microbiota composition that occur in obesity and T2D may impact gut permeability and the presence of bacterial products in AT (34), and methylglyoxal might accumulate in AT, as described in obese rats (35). Whatever the mechanism leading to the high IL-17 production by MAIT cells, this proinflammatory cytokine could influence and participate in the local inflammation of AT.…”

The role of adipose tissue immune cells in obesity and low-grade inflammation

“…end-stage renal disease) (Kremen et al 2006, Roubicek et al 2009). More recently, gut microbiota has been identified as an important modifier of local as well as systemic inflammatory reactions influencing, except of the intestine, also remote tissues, most notably peripheral blood and AT, especially its visceral compartment, where, via the portal vein, intestinal microbial products are being directly drained into (Burcelin et al 2013). Obesity and T2DM were associated with changes in the amount and composition of gut microbes in experimental animals as well as humans (Carvalho & Saad 2013, Cox & Blaser 2013.…”

“…Interestingly, different gut microbiota-derived products can exert both pro-and antiinflammatory effects, as e.g. the translocation of several gut microbial antigens (mainly lipopolysaccharide and peptidoglycans) into systemic circulation leads to metabolic endotoxemia, suggested as one of the main triggers of AT and systemic low-grade inflammation (Burcelin et al 2013, Carvalho & Saad 2013. In contrast, the products of gut bacterial fermentation of ingested dietary fiber, especially short-chain fatty acids (SCFA) -mainly butyrate, propionate, and acetate -were shown to have anti-inflammatory effects and influence energy homeostasis (Kim et al 2014).…”

Microbiotes et maladies métaboliques

“…Le temps de survie des bactéries dans les tissus n'est pas connu. Des fragments d'ADN bactériens sont égale-ment retrouvés dans les organes et le sang chez la souris comme chez l'homme [57][58][59]. Certaines de ces séquences d'ADN sont prédictives de l'apparition du diabète de type 2 [59] tandis que d'autres sont associées à l'apparition d'événements cardiovasculaires [58].…”