Modulation and adherence of intestinal mucus by commensal bacteria and the pathogen C. difficile

Abstract

Gut pathogens initially encounter the host at the gastrointestinal (GI) mucus layer making its regulation a crucial aspect of gut health. Few studies have addressed bacteria‐mucus adherence or mucus oligosaccharide utilization by commensal or pathogenic bacteria. To address this gap in knowledge, the interaction between mucus (human stool, HT‐29‐MTX cells and human ileal enteroids) and commensal bacteria (B. thetaiotaomicron, C. coccoides, C. butryicum, B. producta, A. muciniphila, F. prausnitzii, R. torques, L. reuteri) or the pathogen C. difficile was examined. In vitro cultures in tryptone‐yeast extract media revealed that C. difficile and B. producta were capable of using multiple types of oligosaccharides (fucose, mannose, galactose, GlcNAc, GalNAC, sialic acid) as a sole carbon source, while other commensal bacteria exhibited specific oligosaccharide preferences. Commensal bacteria had enhanced adherence to mucus from human stool compared to HT‐29‐MTX mucus. Additionally, FITC‐labeled oligosaccharide specific lectins demonstrated that all tested commensal bacteria were capable of altering mucus oligosaccharide composition. Select commensal species were also able to stimulate mucus secretion. In contrast, the pathogen C. difficile adhered to multiple oligosaccharides in human stool mucus, but had limited adherence to HT‐29‐MTX mucus. C. difficile did not stimulate mucus secretion in HT‐29‐MTX cells and decreased secretion in enteroids. Together this data demonstrates that commensal and pathogenic bacteria adhere directly to GI mucus, but this interaction is mucin type and composition dependent. Manipulation or adherence to intestinal mucus may represent a method of bacterial‐host modulation. T32DK07644

Clostridioides difficilebinary toxin CDT induces biofilm-like persisting microcolonies

“…C. difficile has previously been shown to adhere to human mucus and to decrease mucin secretion in enteroids 47,48 . In addition, patients with CDI present decreased Muc2 levels and show alterations in mucin composition 48 .…”

“…Pathogens can also induce changes in secretion of mucin by goblet cells [74][75][76] , glycosylation of mucins 77 or reduction in mucus viscosity 78 . Several studies have shown that mucin facilitates C. difficile colonization 37,38,47,48,79 , probably because C. difficile binds to mucus from mice and humans 37,47,67,80,81 48 . They also showed a relationship between patients with recurrent CDI and a decrease of Muc2 and N-acetylgalactosamine (GalNAc) expression, along with an increase of N-acetylglucosamine (GlcNAc) and galactose residues 48 .…”

“…Pathogens can also induce changes in secretion of mucin by goblet cells 74–76 , glycosylation of mucins 77 or reduction in mucus viscosity 78 . Several studies have shown that mucin facilitates C. difficile colonization 37,38,47,48,79 , probably because C. difficile binds to mucus from mice and humans 37,47,67,80,81 . Engevik et al observed that C. difficile strain BAA-1878 can decrease Muc2 secretion when injected in human intestinal organoids (HIOs) 48 .…”