High fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine

High fat diets (HFDs) have been associated with several pathologies. Here we show that HFDs trigger the activation of intestinal stem cells in the Drosophila midgut. This induction of stem cell activation is transient and is preceded by induction of cytokine (upd3) expression in enterocytes. The presence of an indigenous microbiota is essential for the HFD-induced stem cell activation as this response is blunted in germ-free (GF) animals lacking a microbiota. Moreover, both the composition of the microbiota and bacterial load were markedly altered in response to chronic feeding of HFDs to the fly. On the host side, JNK signaling within the enterocytes was essential to transduce the effects of an HFD into substantial stem cell activation. Although the HFD-induced stem cell activity was only transient, a long-lasting shaping of the cellular composition as seen by a substantially increased number of enteroendocrine cells was observed over long time periods. Taken together, HFD enhanced stem cell activities in the gut that completely relied on the presence of an indigenous microbiota and depended on JNK signaling within intestinal enterocytes.