Engineering mucus to study and influence the microbiome

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. Mucus is a 3D hydrogel composed of mucins that houses the human microbiome. Mucus guides microbial cell fate and is involved in the suppression of pathogenic bacteria. In this Review, the authors discuss the design of synthetic mucins for the investigation of mucus–microbiome interactions and for applications in 3D in vitro cell culture.