Molecular interactions between the intestinal microbiota and the host

Abstract

The intestine is the most densely colonized region of the body, inhabited by a diverse community of microbes. The functional significance of the intestinal microbiota is not yet fully understood, but it is known that the microbiota is implicated in numerous physiological processes of the host, such as metabolism, nutrition, the immune system, and regulation of behavior and mood. This article reviews recent findings on how bacteria of the intestinal microbiota interact with the host. Microbiota-microbiota and microbiota-host interactions are mediated by direct cell contact and by metabolites either produced by bacteria or produced by the host or the environment and metabolized by bacteria. Among them are short-chain fatty, including butyrate, propionate, and acetate. Other examples include polyamines, linoleic acid metabolites, tryptophan metabolites, trimethylamine-N-oxide, vitamins, and secondary bile acids. These metabolites are involved in regulating the cell cycle, neurobiological signaling, cholesterol and bile acid metabolism, immune responses, and responses to antioxidants. Understanding the host-microbiota pathways and their modulation will allow the identification of individualized therapeutic targets for many diseases. This overview helps to facilitate and promote further research in this field.

Keywords: auto-immune disease; bile acids; gut permeability; immune system; inflammation; inflammatory bowel disease; microbe-associated molecular patterns; microbiome; short-chain fatty acids.

FIGURE 1

Butyrate action in the intestine. (1) Energy source for colonocytes. As a substrate, induction of gluconeogenesis and cAMP associated genes. (2) Induces prostaglandin production in subepithelial myofibroblasts, which increases the number of goblet cells and mucin production. (3) Increases AMPK activity which leads to augmented tight junction complexes assemblation. (4) Binds to GPR109a on colonocytes, inducing IL‐18 production, which has an anti‐inflammatory action in the colon. (5) Activates PPAR‐γ and vitamin D receptors leading to the inhibition of NF‐κB and reduction of pro‐inflammatory chemokine production. (6) Downregulation of TLR‐4 gene expression in B cells and colonocytes lead to the inhibition of NF‐κB and reduction of pro‐inflammatory chemokine production. (7) Binds on AhR on dendritic cells and macrophages leading to an enhanced IL‐10 production (anti‐inflammatory activity) and histone deacetylase inhibition (reduction of NO, IL‐6 and IL‐12 pro‐inflammatory cytokines production). (8) Decreases the chemotaxis of neutrophils and eosinophils, preventing their infiltration into the mucosal layer. (9) Decreases the number of activated B cells in the cecal lymph nodes and macrophage migration into these nodes. (10) Induces the GLP‐1 and PPY production in enteroendocrine L cells in the colon

FIGURE 2

Tryptophan action in the intestine. In the intestine, the microbiota influences tryptophan metabolism by (1) conversion of tryptophan into indole derivates; several of these derivates are ligands to AhRs, which regulate immune homeostasis, epithelial function, and modulate xenobiotic, antioxidant and hormone‐like estrogen metabolism—AhRs are also involved in prevention colonization by pathogens; (2) the kynurenine pathway in immune and epithelial cells via IDO‐1 induction, which has neurotransmission activity. Kynurenic derivates can be neuroprotective or neurotoxic; (3) serotonin (5‐HT) production in enterochromaffin cells via the induction of tryptophan hydroxylase 1 (Tph‐1), leading to an increase in intestinal motility, intestine‐brain signaling, nutrient absorption, and vasodilatation