Gut commensal bacteria-derived methionine is required for host reproduction by modulating RNA m6a methylation of the insulin receptor

Authors: ZHANG, QUIYUAN - Huazhong Agricultural University; ZHENG, WEIWEI - Huazhong Agricultural University; ZHURONG, DENG - Huazhong Agricultural University; LI, XIAOXUE - Huazhong Agricultural University; QIAO, JIAO - Huazhong Agricultural University; LI, ZINIU - Huazhong Agricultural University; LIU, PEIPEI - Huazhong Agricultural University; Handler, Alfred; LEMAITRE, BRUNO - Ecole Polytechnique Federale De Lausanne (EPFL); ZHANG, HONGYU - Huazhong Agricultural University

Submitted to: Cell Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/5/2025
Publication Date: 6/24/2025
Citation: Zhang, Q., Zheng, W., Zhurong, D., Li, X., Qiao, J., Li, Z., Liu, P., Handler, A.M., Lemaitre, B., Zhang, H. 2025. Gut commensal bacteria-derived methionine is required for host reproduction by modulating RNA m6a methylation of the insulin receptor. Cell Reports. https://doi.org/10.1016/j.celrep.2025.115911.
DOI: https://doi.org/10.1016/j.celrep.2025.115911

Interpretive Summary: The sterile insect technique is a highly effective biologically-based method for controlling the population size of many damaging insect pest species of agricultural importance. This method relies on the field release of mass reared sterile males that mate with females in the field, rendering them non-reproductive. However, mass rearing of tephritid fruit fly species is expensive and optimizing female reproduction is important to the most efficacious use of sterile insect technique. A better understanding of female reproduction may also result in new forms of biological control in the field. To better understand the regulation of oogenesis in tephritid females, scientists at the USDA-ARS in Gainesville, Florida and collaborators at the Huazhong Agricultural University in P.R. China and the École Polytechnique Fédérale de Lausanne in Switzerland, dentified the mechanism by which gut commensal bacteria promote female host reproduction for the oriental fruit fly, Bactrocera dorsalis. This is achieved by the bacterial release of methionine amino acids that result in enhanced ovarian insulin receptor production. Thus, the use of these bacteria as a nutrient source may enhance female reproduction in mass rearing for sterile insect technique, and may provide a target for diminished reproduction in the field.

Technical Abstract: Gut commensal bacteria promote host reproduction by modulating metabolism and nutrition, yet the molecular mechanisms by which microbes modulate reproduction remains unclear. Here, we show that gut commensal bacteria promote host reproduction by providing the amino-acid methionine, which controls RNA m6A modification levels of insulin receptor (InR) in the ovary of the invasive insect Bactrocera dorsalis. RNA m6A levels and S-adenosyl-methionine (SAM) titers in the ovaries were sharply reduced in antibiotic treated B. dorsalis compared with untreated insects, resulting in arrested ovarian development and decreased fecundity. The intestinal commensal bacteria Enterobacter hormaechei or the E. hormaechei-derived metabolite methionine restored the decreased RNA m6A levels and the reproductive defects. Of note, knockdown of the genes encoding the RNA m6A methyltransferases METTL3 and METTL14 resulted in decreased mRNA levels of InR and underdeveloped ovaries in B. dorsalis, and blocked the promoting effect of methionine on ovarian development and fecundity. Collectively, our study identifies an unrecognized role for RNA m6A methylation modification that underlies microbial control of host reproduction. 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.