Study Links Gut Microbiome to Type 1 Diabetes

A new study appearing in Cell Metabolism this week has linked a microbiome-derived protein to pancreatic functioning, revealing a potential role for gut microbiota in type 1 diabetes. Microbiome dysbiosis is a known feature of diabetes, but how microbial products influence insulin production is not well understood. To better understand this relationship, a group from the University of Oregon and collaborators focused on BefA — short for beta cell expansion factor A — a protein secreted by intestinal bacteria they previously showed could increase proliferation of insulin-producing beta cells during development in gnotobiotic zebrafish and mice. They find that BefA can disseminate from the intestine to the pancreas by multiple routes, describe its atomic structure, and show that it permeabilizes synthetic liposomes and bacterial membranes. The researchers also demonstrate that BefA's beta cell-expansion activity is conserved in mice and requires its membrane permeabilization activity, whereas the pore-forming host defense protein Reg3 stimulates beta cell proliferation. "Our work reveals membrane permeabilization as a common mechanism by which both bacterial and host proteins stimulate beta cell expansion," the authors write. The findings also suggest that increased hygiene measures that reduce microbial exposure during early infant life, common in high-income countries that are seeing a surge in type 1 diabetes, may result in mismatched microbial and nutritional developmental cues that could led to the development of the disease.