Impact of Host’s Gut Microbiota on Fertility

Gut microbiome i.e. conglomerates of microbes living in gastrointestinal system, majorly comprises of 4 phyla i.e. Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. A healthy gut is characterized by abundance >90% of Bacteroidetes and Firmicutes species, however lesser F/B ratio is also linked with good health. Metabolites produced by microbes sustains gut microenvironment/maintain homeostasis e.g. butyrate produced by microbes plays immunomodulatory and anti-inflammatory role12. Most research work done on gut microbiome is focused on it’s role in host metabolism while work on their impact on reproduction had been left less studied. Following are the evidences of how microbial imbalance could directly (as in case of polycystic ovary syndrome (PCOS)) and indirectly (via changing hormonal levels), affects fertilization and results in different disorders.

Link between gut microbiome and onset of polycystic ovary syndrome (PCOS):

Consortia of microbes that constitute gut microbiota plays important role in maintaining balance of metabolites, utilization of nutrients and in functioning of immune system. If gut faces microbial imbalance/ dysbiosis, then it could not only contributes to metabolic disorders e.g. obesity, diabetes but also could lead to polycystic ovary syndrome (PCOS). PCOS disorder is related to endocrine system as it involves excessive production of androgens, malfunctioning of ovaries, development of multiple cysts in ovaries, hypothalamic neuronal dysfunction and in many cases leading to infertility. It has recently been shown in a study that as compared to healthy individuals, PCOS affected people possesses much higher microbial diversity especially of Bacteroides vulgatus, whose colonization in gut region becomes abnormally high in PCOS patients. Interestingly, though B.vulgatus is a gram-negative, anaerobic and non-pathogenic commensal of humans but it’s amount in gut has shown to have a direct link in the onset of polycystic ovary syndrome (PCOS). In healthy individuals, phenomenon of bacterial biotransformation occurs and one example of this phenomenon includes bile acids that produced by liver e.g. glycodeoxycholic acid (GDCA) and tauroursodeoxycholic acid (TUDCA) are deconjugated by bacteria e.g. by B.vulgatus. This decreases availability of bile acids for absorption by enterocytes. Bile acids still are available and it binds to TGR5 receptor present on type 3 innate lymphoid cells (ILC3). As a result of this binding, production of interleukin-22 (IL-22) by ILC3 cells is stimulated, which then is essential for maintaining hormone levels, estrous cyclicity as well as metabolic functions. If amount/number of B.vulgatus inhabiting gut exceeds from normal, then availability of GDCA and TGCA for binding to ILC3 cells, drops down significantly as these bile acids absorption via intestinal cells declines. Consequently, GATA3 dependent production of IL-22, would also gets reduced to a greater extent, leading to irregular metabolic activity and polycystic ovary syndrome (PCOS). This phenomenon was studied using adult mice model, to which fecal transplant from PCOS woman resulted in appearance of PCOS associated defects i.e. excessive production of luteinizing hormone (LH), irregularity in reproductive cycles, decline in TUDCA levels and resistance to insulin. Similar results were obtained through administration of B.vulgatus in mice, providing proof that bacterial counts are involved in onset of PCOS. When these mice were treated with IL-22 or GDCA, all that reproductive and metabolic dysfunctions reverted back to normal, thus providing new therapeutic approaches to treat PCOS 13.

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