Discovery of gut microbe’s role in progesterone metabolism offers new fertility insights

Progesterone is a crucial hormone for successful embryo implantation and maintaining a normal pregnancy. Insufficient levels of progesterone are common contributors to IVF treatment failure and early miscarriage. In assisted reproductive treatment, progesterone is typically supplemented through various routes, including oral capsule, vaginal suppositories, or injections, to support luteal function or prepare endometrium for embryo transfer.

However, absorption varies significantly among individuals, particularly with oral administration, and some patients fail to reach sufficient blood and tissue levels of progesterone despite standard or even higher doses, increasing the risk of implantation failure or miscarriage.

In a new study published in Gut Microbes, the research team identified a gut microbe, Clostridium innocuum, in the gut microbiota of infertile women undergoing IVF treatment that disrupts progesterone metabolism, leading to reduced bioavailability of this crucial hormone and potential impacts on female fertility.

Researchers demonstrated that C. innocuum metabolizes progesterone into epipregnanolone, a neurosteroid with minimal progestogenic activity, which significantly lowers circulating progesterone levels through enterohepatic circulation in hosts.

In mouse experiments, the researchers further demonstrated that suppressing this bacterium with targeting antibiotics could help elevate progesterone levels, while prolonged exposure to this bacterium disrupted the estrous cycle and follicular development in mice, as follicular arrest and anovulation in women.

This study not only offers innovative medical strategies for infertility treatment but also strengthens the research foundation on the impact of gut microbiota on reproductive health. Moving forward, the research team aims to apply these findings in clinical settings, working toward a vision of personalized precision medicine.

Progesterone is a crucial hormone for successful embryo implantation and maintaining a normal pregnancy. Insufficient levels of progesterone are common contributors to IVF treatment failure and early miscarriage. In assisted reproductive treatment, progesterone is typically supplemented through various routes, including oral capsule, vaginal suppositories, or injections, to support luteal function or prepare endometrium for embryo transfer.

However, absorption varies significantly among individuals, particularly with oral administration, and some patients fail to reach sufficient blood and tissue levels of progesterone despite standard or even higher doses, increasing the risk of implantation failure or miscarriage.

In a new study published in Gut Microbes, the research team identified a gut microbe, Clostridium innocuum, in the gut microbiota of infertile women undergoing IVF treatment that disrupts progesterone metabolism, leading to reduced bioavailability of this crucial hormone and potential impacts on female fertility.

Researchers demonstrated that C. innocuum metabolizes progesterone into epipregnanolone, a neurosteroid with minimal progestogenic activity, which significantly lowers circulating progesterone levels through enterohepatic circulation in hosts.

In mouse experiments, the researchers further demonstrated that suppressing this bacterium with targeting antibiotics could help elevate progesterone levels, while prolonged exposure to this bacterium disrupted the estrous cycle and follicular development in mice, as follicular arrest and anovulation in women.

This study not only offers innovative medical strategies for infertility treatment but also strengthens the research foundation on the impact of gut microbiota on reproductive health. Moving forward, the research team aims to apply these findings in clinical settings, working toward a vision of personalized precision medicine.