The Rosetta Stone of interactions of mucosa and associated bacteria in the gastrointestinal tract

Abstract

Purpose of review Gut microbiota–mucosa–epithelial cells co-exist in an intricate three-way relationship that underpins gut homeostasis, and ultimately influences health and disease conditions. The O-glycans of mucin glycoproteins have been uncovered as a centrepiece of this system, although understanding the phenomena at play at the molecular level has been challenging and subject to significant traction over the last years. The purpose of this review is to discuss the recent advances in the phenomena that mediate microbiota and mucus multidirectional interactions in the human gut. Recent findings The mucus biosynthesis and degradation by both commensal and pathogenic bacteria is under tight regulation and involves hundreds of carbohydrate-active enzymes (CAZy) and transporters. The fucosylation of O-glycans from mucin-2 seems to dictate binding by pathogenic species and to influence their virulence. Less clear is the influence of O-glycans in quorum sensing and biofilm formation. We have reviewed the advances in the in vitro models available to recreate the phenomena that capture the physiological context of the intestinal environment, emphasising models that include mucus and other aspects relevant to the physiological context. Summary The recent findings highlight the importance of merging advances in analytical (glycans analysis) and omics techniques along with original robust in vitro models that enable to deconstruct part of the high complexity of the living gut and expand our understanding of the microbes-mucosa relationships and their significance in health and disease.

Genomic and functional analysis of the mucinolytic species Clostridium celatum, Clostridium tertium, and Paraclostridium bifermentans

“…In the colon, mucus is produced by goblet cells and organized in two gel layers composed mainly of a net-like structure of MUC2 mucin ( Johansson et al, 2011 ; Bansil and Turner, 2018 ). The outer mucus layer that interacts with the gut content is loose and inhabited by a specific microbiota, whereas the inner layer is much denser, more compact, tightly adhered to the epithelium, and prevents gut microbes from contacting the colon surface and causing inflammation ( Berberolli et al, 2024 ). Impairment of the mucus barrier can allow bacteria to directly contact colorectal epithelial cells, triggering an inflammatory response ( Fekete and Buret, 2023 ).…”

“…Impairment of the mucus barrier can allow bacteria to directly contact colorectal epithelial cells, triggering an inflammatory response ( Fekete and Buret, 2023 ). A healthy mucus layer offers a proper environment that favors mutualistic bacteria and restricts growth of pathogens and pathobionts, providing energy, carbon, and nitrogen sources for herein residing human gut microbes ( Arike and Hansson, 2016 ; Fekete and Buret, 2023 ; Berberolli et al, 2024 ).…”

“…A rich commensal microbial community colonizes the outer mucus layer of the gut, being spatially organized along the length of the intestine as well as from the luminal to mucosal axis. Mucins provide carbon, nitrogen, and energy sources, and select specific microbes able to utilize these substrates ( Arike and Hansson, 2016 ; Berberolli et al, 2024 ). Moreover, O- glycan chains of mucins trap microorganisms and serve as attachment sites for bacteria, preventing them from reaching the epithelial cells ( Bergstrom et al, 2020 ).…”