Gut Commensal Bacteria-Derived Methionine is Required for Host Reproduction by Modulating RNA m6A Methylation of the Insulin Receptor_targeted metabolites

Gut commensal bacteria promote host reproduction by modulating metabolism and nutrition, but the molecular mechanisms by which microbes regulate reproduction remain unclear. Here, we show that gut commensal bacteria promote host reproduction by providing amino-acid methionine, which controls the RNA m6A modification level of insulin receptor (InR) in the ovary of the invasive insect Bactrocera dorsalis. Antibiotic-treated B. dorsalis showed reduced RNA m6A methylation levels and methionine content, resulting in arrested ovarian development and decreased fecundity. Gut commensal bacteria Enterobacter hormaechei-derived metabolite methionine restored the decreased RNA m6A level and the reproductive defects. Notably, knockdown of METTL3 and METTL14, two genes encoding the RNA m6A methyltransferases, reduced InR mRNA and protein levels, and impaired ovarian development of in B. dorsalis. Our findings further expand the functional landscape of m6A modification to include nutrient-dependent control of ovarian development and highlight the essential role of epigenetic regulation in microbe-host interactions.