Study found mucins shape oral #microbiota by serving as nutrients to support metabolic diversity, organizing spatial structure thru reduced aggregation, limiting antagonism between taxa.
Human #microbiome composition is closely tied to health, but how the host manages its microbial inhabitants remains unclear. One important, but understudied, factor is the natural host environment: mucus, which contains gel-forming glycoproteins (mucins) that display hundreds of glycan structures with potential regulatory function. Leveraging a tractable culture-based system to study how mucins influence oral microbial communities, we found that mucin glycans enable the coexistence of diverse microbes, while resisting disease-associated compositional shifts. Mucins from tissues with unique glycosylation differentially tuned microbial composition, as did isolated mucin glycan libraries, uncovering the importance of specific glycan patterns in microbiome modulation. We found that mucins shape microbial communities in several ways: serving as nutrients to support metabolic diversity, organizing spatial structure through reduced aggregation, and possibly limiting antagonism between competing taxa. Overall, this work identifies mucin glycans as a natural host mechanism and potential therapeutic intervention to maintain healthy microbial communities.
The human body harbors trillions of diverse microbes in complex communities across our mucosal surfaces, which exhibit remarkable stability over time. Maintaining microbial homeostasis is essential to human health, but host mechanisms to select for beneficial members and establish coexistence between competing microbes are poorly understood. Our microbiotas predominantly reside in mucus, a complex viscoelastic matrix that coats all non-keratinized epithelial surfaces in the body. Disruptions in mucus including altered viscoelasticity and glycosylation are associated with numerous pathologies1,2,3,4 and microbiome imbalance (dysbiosis)2,5,6,7, highlighting the importance of an intact mucus barrier for health. Many structural and biological functions of mucus center around mucins, large glycoproteins comprised of a peptide backbone densely coated with distinct branching sugar chains (glycans) (Fig. 1a). Mucins can interact with microbes in various ways. For instance, bacteria that encode machinery to degrade complex carbohydrates can utilize whole mucus8,9 or purified mucin10,11 as a nutrient source. Mucin can also bind to microbes12,13,14 and mediate their spatial organization15. Moreover, mucins and their chemically-diverse O-linked glycans can influence microbial behaviors including biofilm formation16,17,18, communication16, and competition18,19. These numerous functions suggest a critical role for mucins in maintaining microbial homeostasis, but mucins’ impact in the context of complex microbial communities is largely understudied. Recently, mice fed a diet supplemented with mucin glycans were shown to exhibit differences in microbial composition20, opening new questions on the importance of mucin glycan biochemistry, and the underlying mechanisms of interaction with microbes.
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