Exploring the impact of intestinal ion transport on the gut microbiota

Abstract

The gut microbiota and the host are intimately connected. The host physiology dictates the intestinal environment through regulation of pH, ion concentration, mucus production, etc., all of which exerts a selective pressure on the gut microbiota. Since different regions of the gastrointestinal tract are characterized by their own physicochemical conditions, distinct microbial communities are present in these locations. While it is widely accepted that the intestinal microbiome influences the host (tight junctions, cytokine/immune responses, diarrhea, etc.), the reciprocal interaction of the host on the microbiome is under-explored. This review aims to address these gaps in knowledge by focusing on how the host intestinal ion transport influences the luminal environment and thereby modulates the gut microbiota composition.

Keywords: CFTR; CFTR, cystic fibrosis transmembrane regulator; ClC, chloride channel; DRA; DRA, down-regulated in adenoma; ENaC, epithelial Na+ channel; GI, gastrointestinal; GLUT2; GLUT2, glucose transporter 2; Gastrointestinal; Ion transport; Microbiome; Microbiota; NHE2; NHE2, sodium-hydrogen exchanger isoform 2; NHE3; NHE3, sodium-hydrogen exchanger isoform 3; NKCC1, Na+-K+-2Cl− co-transporter; OTUs, operational taxonomic units; SGLT1, sodium glucose co-transporter 1.

Fig. 1

Graphical representation of the intestinal tract of humans and mice. Both human and mouse intestine can be separated into small and large intestine (also known as colon). Humans and mice have 3 segments of the small intestine: duodenum, jejunum and ileum. The cecum of humans is a small pouch at the beginning of the colon and is connected to the appendix. The cecum of mice is a large fermentation region that is distinct from both small and large intestine. In both humans and mice, the colon is segmented into different regions with distinct structures and function.

Fig. 2

Graphical representation of intestinal ion transport. Transport mechanisms in the small intestine and colon are depicted. As shown, ion transporters are differentially distributed, creating unique microenvironments. These transporters are present in mouse and human.

Fig. 3

Graphical representation of the microbiome composition along the length of the intestine. Pie graphs depict the relative abundance of the major phyla (Firmicutes (pink), Bacteroidetes (yellow), Actinobacteria (blue), Verrucomicrobia (green), Fusobacteria (fusia), Proteobacteria (orange) and other (grey)). Composition is noted for both the luminal population as well as the mucosa-associated microbiome for human and mouse. Composition is approximated from published literature. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Graphical representation of the microbiome of WT type mice highlighting the communities in the ileum and colon, for both luminal and mucosa-associated communities. Pie graphs depict the relative abundance of the major phyla (Firmicutes (pink), Bacteroidetes (yellow), Actinobacteria (blue), Verrucomicrobia (green), Fusobacteria (fusia), Proteobacteria (orange) and other (grey)). In contrast to WT mice, NHE3, NHE2, CFTR, DRA and GLUT2 knockout (KO) mice harbor an altered intestinal environment and bacterial populations. Composition is approximated from published literature. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)