Gut Microbiome-Based Therapies May Improve Fertility, Preclinical Study Hints

Aging leads to the dwindling of ovarian health, which reshapes hormone rhythms to reduce fertility. Despite this process being linked to aging-related diseases such as osteoporosis and dementia, scientists do not fully understand the molecular mechanisms underlying ovarian aging.¹ This impedes the development of treatment options to boost ovarian health.

Now, bridging this gap, researchers found that fecal transplants from older female mice improved ovarian function and fertility in young mice.² The findings, published in Nature Aging, reveal a link between the gut microbiome and ovarian health, hinting at the potential of microbiome-based treatments for ovarian aging.

“These findings suggest that there is two-way communication between the ovary and the microbiome and that this communication changes throughout life with age,” said study coauthor Bérénice Benayoun, a gerontologist at the University of Southern California, in a statement.

A few recent reports suggested that the gut microbiome influences ovarian health.^3,4 So, Benayoun and her team assessed the fecal microbiota of young adult female mice or older estropausal mice, which are in a post-reproductive state corresponding to menopause in humans. 16S rRNA sequencing revealed distinct fecal microbial profiles in young and older mice, indicating that ovarian aging induces gut microbial shifts.

To investigate how gut microbiota alterations influence ovarian health, Benayoun and her team transplanted fecal microbiota from either young or older estropausal mice into young recipients. Analyzing the transcriptomes of recipient animals’ ovaries revealed that the tissues of mice that received older microbiomes resembled those of much younger animals. These cells showed reduced pro-inflammatory cytokine expression and a spike in anti-inflammatory cytokine expression.

This transcriptional remodeling mimicking a youthful ovarian state also corresponded to enhanced ovarian function in terms of fertility. Compared to mice that received younger microbiomes, those that received estropausal microbiomes gave birth to higher numbers of offspring.

“Our original hypothesis was that we would see damaging effects of the older microbiome on ovarian function, but surprisingly, we found the opposite,” said study coauthor Min Hoo Kim, a postdoctoral researcher in the Benayoun lab, in the statement.

To dig into why older microbiomes rejuvenated ovarian health and function, Benayoun and her team compared the microbiome profiles of mice that received fecal transplants. Shotgun metagenomics and 16S rRNA sequencing identified distinct microbial species and their metabolites between animals that received young and estropausal microbiomes. Metabolomic analyses further revealed that fecal transplant from estropausal donors induced distinct metabolic shifts that could influence ovarian health.

The authors noted that more work needs to be done to determine whether microbiome-based therapies could one day support fertility and healthy aging in women.

“Menopause isn’t just about no longer being fertile,” said Benayoun, noting that menopause increases risks of other age-associated diseases. “If we could effectively delay menopause, it would help women live longer, healthier lives,” she said.