Normalization of Host Intestinal Mucus Layers Requires Long-Term Microbial Colonization

Abstract

SUMMARY The intestinal mucus layer provides a barrier limiting bacterial contact with the underlying epithelium. Mucus structure is shaped by intestinal location and the microbiota. To understand how commensals modulate gut mucus, we examined mucus properties under germ-free (GF) conditions and during microbial colonization. Although the colon mucus structure of GF mice was similar to conventionally raised (Convr) mice, the GF inner mucus layer was penetrable to bacteria-sized beads. During colonization, in which GF mice were gavaged with Convr microbiota, the small intestine mucus required five weeks to be normally detached and colonic inner mucus six weeks to become impenetrable. The composition of the small intestinal microbiota during colonization was similar to Convr donors until three weeks when Bacteroides increased, Firmicutes decreased, and segmented filamentous bacteria became undetectable. These findings highlight the dynamics of mucus layer development and indicate that studies of mature microbe-mucus interactions should be conducted weeks after colonization.

Environmental spread of microbes impacts the development of metabolic phenotypes in mice transplanted with microbial communities from humans

“…The mucin-degrading bacterium Akkermansia (Everard et al, 2013) increased in abundance after the early colonisation phase. This is in agreement with the finding that the mucus layer in the gut of GF mice in not mature, and that during colonisation, the ileal mucus becomes more detached, increasing the relative amount of available mucin in the colon (Johansson et al, 2015). Interestingly, human donors were distinguished from transplanted mice by harbouring a cluster of genera, many of which are potential butyrate producers, including Roseburia, Eubacterium (within the family Eubacteriaceae), Coprococcus, Faecalibacterium, Pseudobutyrivibrio and Lachnospira (Rode et al, 1981;Pryde et al, 2002;Paillard et al, 2007;Louis and Flint, 2009).…”

High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine

“…The few studies analyzing the potential symbiotic relationship between specific commensal bacteria and SFB indicate that members of the Bacteroides/Prevotella or Lactobacillus genus may be key to explain its maintenance and abundance in infants and mice, respectively (77,78). Moreover, a recent paper shows that decrease of SFB in the ileum corresponds to an increase of the Erysipelotrichi class (79). Here, the decrease in Bacteroides and the appearance of Erysipelotrichi could explain the loss of SFB.…”

Polymers in the gut compress the colonic mucus hydrogel

“…To probe the in vivo thickness of murine colonic mucus, we developed a labelfree technique that eliminates evaporation and avoids the use of any washing, fixative, labeling, or dehydrating agents that could alter mucus structure (SI Materials and Methods). We used freshly excised colon explants obtained from mice at least 8 wk oldwhose mucus hydrogel has been found to be fully developed and stable (20)-and gently removed the luminal contents using FC-40 oil, a fluorocarbon fluid that is immiscible with, and denser than, water. We opened each explant along the intestinal axis and mounted it flat, with its luminal surface facing upward and coated with FC oil.…”