Synthetic Colonic Mucus Enables the Development of Modular Microbiome Organoids

The human colon is home to trillions of microorganisms that modulate gastrointestinal physiology. Our understanding of how this gut ecosystem impacts human health, although evolving, has been slowed by the lack of accessible tools suitable to studying complex host-mucus-microbe interactions. Here, we report a synthetic gel-like material capable of recapitulating the varied structural, mechanical, and biochemical profiles of native human colonic mucus to develop compositionally simple microbiome screening platforms with utility in microbiology and drug discovery. The viscous fibrillar material is realized through templated assembly of a fluorine-rich amino acid at liquid-liquid interphases. The fluorine-assisted mucus surrogate (FAMS) can be decorated with mucins to serve as a habitat for microbial colonization and integrated with human colorectal cells to generate artificial mucosae, referred to as a microbiome organoid. Notably, FAMS are made with inexpensive and commercially available materials, and can be generated using simple protocols and standard laboratory hardware. As a result, this platform can be broadly incorporated into various laboratory settings to advance probiotic research and inform in vivo approaches. If implemented into high throughput screening approaches, FAMS may represent a valuable tool to study compound metabolism and gut permeability, with an exemplary demonstration of this utility presented here.