the intestinal microbiota is required for normal expansion of the pancreatic β-cell population

The role of the host-associated microbiota in promoting the development of the animal gastrointestinal tract is well established; however, the influence of resident microorganisms on the development of other digestive organs has remained elusive. In this paper, Hill et al. show that the intestinal microbiota is required for normal expansion of the pancreatic β-cell population in zebrafish during early larval development.

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In the first few days after hatching, the number of insulin-producing β-cells in zebrafish larvae increases steadily; by contrast, the authors found that germ-free zebrafish maintained the same number of β-cells as they had before hatching. Mono-colonization of the germ-free animals with Aeromonas spp. isolated from the zebrafish gut restored their β-cell populations, whereas other species such as Vibrio spp. did not rescue this phenotype. Importantly, the authors were able to identify a previously unknown secreted protein that is produced by Aeromonas spp. that induced β-cell expansion, which they termed β-cell expansion factor A (BefA). Moreover, the data suggest that BefA causes β-cell expansion by increased cell proliferation, but it remains to be determined whether this proliferation occurs in progenitor cells, mature β-cells or both.

Finally, homologues of BefA produced by members of the human gut microbiota also induced β-cell proliferation in germ-free zebrafish, which suggests that this factor has a conserved role in early development. In summary, this study reveals the important role of the microbiota in organ development beyond the intestine.