Host-Gut Microbiota Crosstalk in Intestinal Adaptation

Abstract

Short-bowel syndrome represents the most common cause of intestinal failure and occurs when the remaining intestine cannot support fluid and nutrient needs to sustain adequate physiology and development without the use of supplemental parenteral nutrition. After intestinal loss or damage, the remnant bowel undergoes multifactorial compensatory processes, termed adaptation, which are largely driven by intraluminal nutrient exposure. Previous studies have provided insight into the biological processes and mediators after resection, however, there still remains a gap in the knowledge of more comprehensive mechanisms that drive the adaptive responses in these patients. Recent data support the microbiota as a key mediator of gut homeostasis and a potential driver of metabolism and immunomodulation after intestinal loss. In this review, we summarize the emerging ideas related to host-microbiota interactions in the intestinal adaptation processes.

Keywords: Adaptive Responses; CONV, conventional; ENS, enteric nervous system; Enteric Flora; GF, germ-free; GI, gastrointestinal; GLP-2, glucagon-like peptide 2; IBD, inflammatory bowel disease; ICR, ileocecal resection; IF, intestinal failure; IL, interleukin; Immune System; Intestinal Failure; Microbial Metabolites; NEC, necrotizing enterocolitis; PN, parenteral nutrition; SBR, small bowel resection; SBS, short-bowel syndrome; SCFA, short-chain fatty acid; SFB, segmented filamentous bacteria; TGR5, Takeda-G-protein-receptor 5.

Figure 1

Microbiota and microbiota-derived metabolites effects on intestinal layers. Bacteria have the ability to modulate local and systemic environments through direct or indirect pathways. For example, in the small intestine (ileum), commensal SFB bacteria can adhere directly to the epithelial cell and trigger the immune responses. In the colon, A municiphila can reach the epithelial cells by degrading the mucus layers, and promote enterocyte proliferation and wound healing. Indirectly, microbial AhR ligands are able to induce mucosal healing and antimicrobial production through ILC3-mediated IL22 secretion. The microbial-derived SCFA can promote intestinal adaptation, modulate immune responses, and alter gut motility through the activation of G-protein–coupled receptors (eg, GPR41, GPR43, and the butyrate-specific GPR109A) or HDAC inhibition. Activation of GPR41/43 or TGR5 receptor induce the release of 5-HT and GLP-1 from enteroendocrine cells and alters colonic transit. Bile acids also can modulate gut motility by activating the TGR5 receptor on enteric neurons. AhR, aryl hydrocarbon receptor; ChAT, choline acetyltransferase; DC, dendritic cell; 5-HT, serotonin; GLP-1, glucagon-like peptide 1; HDAC, histone deacytalse; ILC3, innate lymphoid cell 3; SAA, serum amyloid A; Th, T-helper cell; Treg, regulatory T cell; TRP, tryptophan.