{"doi":"10.1101/2022.03.24.485696","title":"A microbiota membrane disrupter disseminates to the pancreas and increases β-cell mass","abstract":"Summary Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. Here we report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β-cells during pancreatic development in gnotobiotic zebrafish and mice. BefA disseminates systemically via multiple anatomic routes to act directly on pancreatic islets. We report the structure of BefA, 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 defense proteins is necessary and sufficient for β-cell expansion during pancreas development, thereby connecting microbiome composition with diabetes risk.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":306702,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":746302,"name":"Michelle S. Massaquoi","orcid":"0000-0002-1364-5866","position":1,"is_corresponding":false},{"id":681431,"name":"Emily Goers Sweeney","orcid":"0000-0002-5539-8875","position":2,"is_corresponding":false},{"id":273703,"name":"Elena S. Wall","orcid":"0000-0001-5120-0801","position":3,"is_corresponding":false},{"id":878600,"name":"Philip Jahl","orcid":"0000-0002-3544-5259","position":4,"is_corresponding":false},{"id":623183,"name":"Rickesha Bell","orcid":"0000-0002-0554-0730","position":5,"is_corresponding":false},{"id":879179,"name":"Karen Kallio","orcid":null,"position":6,"is_corresponding":false},{"id":879180,"name":"Daniel Derrick","orcid":null,"position":7,"is_corresponding":false},{"id":878601,"name":"L. Charles Murtaugh","orcid":"0000-0001-7353-4706","position":8,"is_corresponding":false},{"id":273704,"name":"R. Parthasarathy","orcid":"0000-0002-6006-4749","position":9,"is_corresponding":false},{"id":682516,"name":"S. James Remington","orcid":null,"position":10,"is_corresponding":false},{"id":253554,"name":"June L. Round","orcid":"0000-0002-7158-9874","position":11,"is_corresponding":false},{"id":273705,"name":"Karen Guillemin","orcid":"0000-0001-6004-9955","position":12,"is_corresponding":false},{"id":649592,"name":"Jennifer Hampton Hill","orcid":"0000-0002-5544-1423","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:32:52.703737Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}