Host–microbiota interaction induces bi-phasic inflammation and glucose intolerance in mice

Objective: Gut microbiota modulates adiposity and glucose metabolism in humans and mice. Here we investigated how colonization of germ-free (GF) mice affects kinetics of adiposity and glucose metabolism. Methods: Adiposity and glucose metabolism were evaluated at different time points in ex-GF and antibiotic treated mice after colonization with gut microbiota from a conventionally raised (CONV-R) mouse. Mouse physiology, microbiome configuration, serum cytokine levels, and gene expression for inflammatory markers were performed in different tissues. Results: Colonization resulted in a bi-phasic glucose impairment: the first phase occurring within 3 days of colonization (early phase) and the second 14–28 days after colonization (delayed phase). The early phase co-occurred with an inflammatory response and was independent of adiposity, while the delayed phase was mostly ascribed to adipose tissue expansion and inflammation. Importantly, re-colonization of antibiotic treated mice displays only the delayed phase of glucose impairment and adiposity, suggesting that the early phase may be unique to colonization of the immature GF mice gut. Conclusions: Our results provide new insights on host–microbiota interaction during colonization of GF mice and the resulting effects on adiposity and glucose metabolism in a time resolved fashion

Gastrointestinal tract: microbial metabolism of steroids

The human gastro-intestinal tract hosts a complex and diverse microbial community, whose microbiome encodes biochemical pathways that humans have not evolved. As a consequence, the gut microbiota produces metabolites from a large range of molecules that host’s enzymes are not able to convert. This is of first importance as these bacterial metabolites may have beneficial or deleterious effects on human health. In particular, cholesterol and bile acids are exposed to the gut microbiota and undergo bacterial metabolism: cholesterol is mainly converted into coprostanol, a non absorbable sterol which is excreted in the feces. Conversely, over twenty different secondary bile acid metabolites are produced by the gut microbiota from the primary bile acids: cholic and chenodeoxycholic acids. The main bile salt conversions in the human gut include deconjugation, oxidation and epimerization of hydroxyl groups at C3, C7 and C12, 7-dehydroxylation, esterification and desulfatation