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  • Review Article
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Engineering mucus to study and influence the microbiome

Abstract

Mucus is a 3D hydrogel that houses the majority of the human microbiome. The mucous environment plays an important role in the differentiation and behaviour of microbial phenotypes and enables the creation of spatial distributions. Dysregulation of mucus is further associated with various diseases. Therefore, mucus is the key ingredient to study the behaviour of commensal and pathogenic microbiota in vitro. Indeed, microorganisms cultured in mucus exhibit phenotypes substantially different from those exhibited in standard laboratory media. In this Review, we discuss the impact of mucus on the microbiome and examine the structure and glycosylation of mucins — the main building blocks of mucus. We investigate the impact of glycans on mucin function and highlight different approaches for the engineering of synthetic mucins, including synthesis of the backbone, the design of mucin-mimetic hydrogels and the engineering of glycans. Finally, mucin mimetics for 3D in vitro cell culture and for modulating microbial community structure and function are discussed.

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Fig. 1: Mucus houses the microbiota.
Fig. 2: Mucin glycoproteins contain a library of complex glycans.
Fig. 3: Mucin gels influence microbial phenotypes.
Fig. 4: Synthetic mucins.
Fig. 5: Potential applications of mucin mimetics.

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Acknowledgements

This work was supported by the US National Institutes of Health under award NIH R01-EB017755, the US National Science Foundation under award NSFCareerPHY-1454673 and the Materials Research Science and Engineering Centers (MRSEC) Program of the US National Science Foundation under award DMR-14-19807. C.W. was supported in part by the US National Science Foundation Graduate Research Fellowship Program under grant no. 1122374.

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Werlang, C., Cárcarmo-Oyarce, G. & Ribbeck, K. Engineering mucus to study and influence the microbiome. Nat Rev Mater 4, 134–145 (2019). https://doi.org/10.1038/s41578-018-0079-7

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