Figure 2.

Major mechanisms involved in the crosstalk between microbes and host: impact of metabolism. The balance between healthy and pathological situations (eg, metabolic disorders) is crucial. This is under the tight influence of several factors including the genes, food and drugs. This left part of the figure shows that in healthy situation, the composition of the gut microbiome is associated with a higher mucus layer thickness, the production of antimicrobial signals and different short-chain fatty acids such as butyrate and propionate. Both butyrate and propionate bind to G protein coupled receptors (GPR)-43 and GPR-41 expressed on the enteroendocrine L-cells thereby stimulating the secretion of gut peptides such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). This effect contributes to reduce food intake and to improve glucose metabolism. Propionate can also bind to GPR-43 expressed on lymphocytes in order to maintain appropriate immune defence. Butyrate activates peroxisome proliferator-activated receptor-γ (PPAR-γ) leading to beta-oxidation and oxygen consumption, a phenomenon contributing to maintain anaerobic condition in the gut lumen. As depicted on the right part of the figure, during metabolic disorders, changes in the gut microbiome are linked with a lower mucus thickness, decreased antimicrobial defense and butyrate and propionate production. As a consequence, L-cells secrete less gut peptides. The lack of PPAR-γ activation lead to higher oxygen available for the microbiota at the proximity of the mucosa and increases the proliferation of Enterobacteriaceae. The decrease in propionate also contribute to the lower abundance of specific T cells (mucosal-associated invariant T cells (MAIT) and Treg) in the lamina propria of the gut. Altogether, such changes in the microbial environment and metabolites induce a leakage of pathogen associated molecular patterns (PAMPs) such as the lipopolysaccharide (LPS) that are increased in the blood, and trigger low-grade inflammation.