Department of Biomolecular Sciences, Weizmann Institute of Science, 7670001 Rehovot, Israel.
Department of Biomolecular Sciences, Weizmann Institute of Science, 7670001 Rehovot, Israel.
Cell Rep. 2021 Jan 5;34(1):108583. doi: 10.1016/j.celrep.2020.108583.
Gut microbiota have been shown to promote oogenesis and fecundity, but the mechanistic basis of remote influence on oogenesis remained unknown. Here, we report a systemic mechanism of influence mediated by bacterial-derived supply of mitochondrial coenzymes. Removal of microbiota decreased mitochondrial activity and ATP levels in the whole-body and ovary, resulting in repressed oogenesis. Similar repression was caused by RNA-based knockdown of mitochondrial function in ovarian follicle cells. Reduced mitochondrial function in germ-free (GF) females was reversed by bacterial recolonization or supplementation of riboflavin, a precursor of FAD and FMN. Metabolomics analysis of GF females revealed a decrease in oxidative phosphorylation and FAD levels and an increase in metabolites that are degraded by FAD-dependent enzymes (e.g., amino and fatty acids). Riboflavin supplementation opposed this effect, elevating mitochondrial function, ATP, and oogenesis. These findings uncover a bacterial-mitochondrial axis of influence, linking gut bacteria with systemic regulation of host energy and reproduction.
肠道微生物群已被证明可以促进卵子发生和生育能力，但远程影响卵子发生的机制基础仍不清楚。在这里，我们报告了一种由细菌衍生的线粒体辅酶供应介导的全身性影响机制。微生物组的去除降低了全身和卵巢中的线粒体活性和 ATP 水平，导致卵子发生受到抑制。卵巢滤泡细胞中线粒体功能的 RNA 敲低也导致了类似的抑制。无菌（GF）雌性的线粒体功能降低可通过细菌再定植或核黄素（FAD 和 FMN 的前体）的补充来逆转。对 GF 雌性的代谢组学分析显示，氧化磷酸化和 FAD 水平降低，而依赖 FAD 的酶降解的代谢物（例如氨基酸和脂肪酸）增加。核黄素补充剂则起到了相反的作用，提高了线粒体功能、ATP 和卵子发生。这些发现揭示了一种细菌-线粒体影响轴，将肠道细菌与宿主能量和生殖的全身调节联系起来。
