Fecal Microbiota Transplantation Improves Ovarian Function in Old Mice

Fecal microbiota transplantation from a young individual to an old individual has been shown in animal studies to reset the aging gut microbiome to a more youthful configuration for a lasting period of time. The gut microbiome changes in detrimental ways with age, harmful and inflammatory populations displacing beneficial populations that produce needed metabolites. A fecal microbiota transplant removes these changes, improving health, reducing inflammation, and extending life span in short-lived species. It is a procedure already used in humans, and which should be further developed as a means to improve the health of all older people.

Advanced maternal age is characterized by declines in the quantity and quality of oocytes in the ovaries, and the aging process is accompanied by changes in gut microbiota composition. However, little is known about the relationship between gut microbiota and ovarian aging. By using fecal microbiota transplantation (FMT) to transplant material from young (5-week-old) into aged (42-week-old) mice, we find that the composition of gut microbiota in FMT-treated mice presents a "younger-like phenotype" and an increase of commensal bacteria, such as Bifidobacterium and Ruminococcaceae. Moreover, the FMT-treated mice show increased anti-inflammatory cytokine IL-4 and decreased pro-inflammatory cytokine IFN-γ.

Fertility tests for assessing ovarian function reveal that the first litter size of female FMT-treated mice is significantly higher than that of the non-FMT group. Morphology analysis demonstrates a dramatic decrease in follicle atresia and apoptosis as well as an increase in cellular proliferation in the ovaries of the FMT-treated mice. Our results also show that FMT improves the immune microenvironment in aged ovaries, with decreased macrophages and macrophage-derived multinucleated giant cells (MNGCs). These results suggest that FMT from young donors could be a good choice for delaying ovarian aging.

Link: https://doi.org/10.1016/j.jgg.2022.05.006

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