BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases β cell mass.

ABSTRACT: Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. We report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets. We detail BefA's atomic structure, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand β cells, whereas the pore-forming host defense protein, Reg3, stimulates β cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defen

SUBMITTER: Hill JH 

PROVIDER: S-EPMC9633563 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature