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

Abstract

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. 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. 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.