Home, sweet home: how mucus accommodates our microbiota

Abstract

As a natural environment for human-microbiota interactions, healthy mucus houses a remarkably stable and diverse microbial community. Maintaining this microbiota is essential to human health, both to support the commensal bacteria that perform a wide array of beneficial functions and to prevent the outgrowth of pathogens. However, how the host selects and maintains a specialized microbiota remains largely unknown. In this viewpoint, we propose several strategies by which mucus may regulate the composition and function of the human microbiota and discuss how compromised mucus barriers in disease can give rise to microbial dysbiosis.

Keywords: microbial dysbiosis; microbiota; mucin glycans; mucins; mucus.

Fig. 1.

Overview schematic of microbial communities in healthy and diseased mucus. (A) Healthy mucus selects for and maintains a diverse, yet specific, microbial community. (B) Diseases with compromised mucus barriers are often associated with microbial dysbiosis.

Fig. 2.

Mucin glycoproteins are the primary structural component of mucus gels. Mucin monomers are densely grafted with diverse and complex glycans. Shown are representative glycan structures isolated from MUC5AC, as identified by mass spectrometry.

Fig. 3.

Proposed mechanisms of influence of mucins on microbial communities. A. Mucin glycans are a source of diverse and complex nutrients, which can metabolically shape the microbiota. Glycans may select for beneficial microbes which produce specific glycosidases, as well as facilitate cooperation across species which produce complementary degradative enzymes. B. Mucin networks may spatially organize bacterial communities in several ways, including by directly binding microbes, by altering group behaviors such as aggregation, or by impacting the transport of nutrients, host immune factors, and/or signaling molecules which may shape the assembly of microbial communities. C. Mucin glycans act through regulatory signaling pathways to attenuate virulent behavior. In the presence of mucins, potentially pathogenic microbes may sense and respond to mucin glycans, which enables their transition a host-compatible state within a healthy community. Without mucin regulation, aggressive microbes may overtake the community, forming a dysbiotic microbiota.