title: A conserved bacterial protein induces pancreatic beta cell expansion during zebrafish development.
abstract: Resident microbes play important roles in the development of the gastrointestinal tract, but their influence on other digestive organs is less well explored. Using the gnotobiotic zebrafish, we discovered that the normal expansion of the pancreatic β cell population during early larval development requires the intestinal microbiota and that specific bacterial members can restore normal β cell numbers. These bacteria share a gene that encodes a previously undescribed protein, named herein BefA (β Cell Expansion Factor A), which is sufficient to induce β cell proliferation in developing zebrafish larvae. Homologs of BefA are present in several human-associated bacterial species, and we show that they have conserved capacity to stimulate β cell proliferation in larval zebrafish. Our findings highlight a role for the microbiota in early pancreatic β cell development and suggest a possible basis for the association between low diversity childhood fecal microbiota and increased diabetes risk.
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, United States.
authors.forename: Jennifer Hampton
authors.initials: JH
authors.lastname: Hill
authors.affiliation: Biostatistics Department, Harvard T. H. Chan School of Public Health, Boston, United States.|The Broad Institute, Cambridge, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Franzosa
authors.affiliation: Biostatistics Department, Harvard T. H. Chan School of Public Health, Boston, United States.|The Broad Institute, Cambridge, United States.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.affiliation: Institute of Molecular Biology, University of Oregon, Eugene, United States.|Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Canada.
authors.forename: Karen
authors.identifier: 0000-0001-6004-9955
authors.initials: K
authors.lastname: Guillemin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology*; D010179:Pancreas / Q000196:embryology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D001426:Bacterial Proteins
keywords: beta cells; development; developmental biology; infectious disease; microbiology; microbiota; stem cells; zebrafish