Infertility is becoming more common worldwide, affecting about one in six people. Now, a study in mice shows that early life is a critical window where diet and gut microbes shape reproductive health.

The findings, published in Cell Host & Microbe, suggests that dietary fiber is a potential fertility-support strategy.

Recent research has indicated that the microbiota plays a key role in reproduction by supporting growth, development, and egg production. In humans, changes to the microbiota caused by antibiotics, diet or conditions such as obesity are linked to reproductive problems, but the exact reasons remain unclear. 

Sarah Munyoki at the University of Pittsburgh School of Medicine in Pennsylvania and her colleagues set out to examine how gut microbes and diet during early life affect fertility in mice.

Ovarian health

In normal mice, the gut microbiota shifts after birth, especially during weaning, becoming richer and more complex. Early on, the gut is dominated by bacteria adapted to breast milk, but after weaning, microbes that break down solid food and produce beneficial compounds such as short-chain fatty acids (SCFAs) expand. Female mice raised without gut microbes showed disruptions in ovarian development that coincided with this microbiota transition, the researchers found.

Compared to mice with a healthy microbiota, female mice raised without microbes had fewer litters and fewer pups per litter, and they stopped reproducing earlier in life. By puberty, germ-free mice began losing follicles much faster than mice with a healthy microbiota, with poor progression to later stages and higher rates of follicle death. 

The ovaries of germ-free mice showed damage, with signs of tissue scarring. Genetic analysis revealed that key genes for maintaining and activating ovarian follicles—the reserve needed for producing eggs—were less active than in mice with a healthy microbiota.

Improving fertility

Giving germ-free female mice normal gut microbes either at birth  or at weaning restored the follicles to normal levels and reversed tissue damage. This recovery matched a return of normal gut bacteria diversity and production of SCFAs. Just giving germ-free mice SCFAs in drinking water starting at weaning rescued ovarian health, at least in part.

Finally, the researchers fed mice different diets starting at weaning. High-fat, low-fiber diets caused the biggest loss of ovarian follicles and altered ovarian gene activity, while adding fiber helped protect ovaries, even in high-fat conditions. Fiber also improved gut bacteria, boosted SCFAs levels, and reduced inflammation in ovaries. 

The findings suggest that dietary fiber during early life protects fertility by supporting healthy gut microbes and preventing ovarian damage caused by high-fat diets, the authors say. “Future studies should examine the relationship between diet, microbiota, and ovarian reserve in individuals with reproductive disorders and assess the efficacy of microbiota-directed interventions in improving fertility outcomes.”