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.DOI: http://dx.doi.org/10.7554/eLife.20145.001

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Regulation of the microbiota is critical to intestinal health yet the mechanisms employed by innate immunity remain unclear. Here we show that mice deficient in the C-Type-lectin receptor, Clec12a developed severe colitis, which was dependent on the microbiota. Fecal-microbiota-transplantation (FMT) studies into germfree mice revealed a colitogenic microbiota formed within Clec12a-/- mice that was marked by expansion of the gram-positive organism, Faecalibaculum rodentium. Treatment with F. rodentium was sufficient to worsen colitis in wild-type mice. Macrophages within the gut express the highest levels of Clec12a. Cytokine and sequencing analysis in Clec12a-/- macrophages revealed heighten inflammation but marked reduction in genes associated with phagocytosis. Indeed, Clec12a-/- macrophages are impaired in their ability to uptake F. rodentium. Purified Clec12a had higher binding to gram-positive organisms such as F. rodentium. Thus, our data identifies Clec12a as an innate immune surveillance mechanism to control expansion of potentially harmful commensals without overt inflammation.

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