The gut microbiome is clearly important to health, and changes in the composition of the gut microbiome influence the progression of degenerative aging to a meaningful degree. Gut microbes of various species generate useful or harmful metabolites that interact with cells in the body. The aging of the gut microbiome is now known to reduce the supply of some useful metabolites, while increasing inflammatory interactions with the immune system. It is possible to restore a more youthful composition to the gut microbiome via a number of different approaches. Flagellin immunization encourages the immune system to more aggressively remove problematic microbial species that have grown in number with age, while fecal microbiota transplantation from a young donor to an old recipient directly resets the composition of the gut microbiome to a more youthful state.
Researchers are continuing to identify specific metabolites relevant to health and aging and the species that produce them. This will ultimately give rise to new strategies to improve health, such as supplementation of beneficial metabolites, selective removal or introduction of specific microbial species, or the tailored creation of entire new synthetic gut microbiomes that can be provided to patients. Today’s open access paper is an example of the sort of research presently taking place, in which researchers identify glutamic acid as a metabolite important to oocyte quality in the aging ovaries. While provided by the gut microbiome, short term supplementation of glutamic acid does just as good a job as changes to the microbiome when it comes to restoring lost oocyte quality in old female mice.
The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility.
By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.
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