Emerging evidence reported in the journal Nature Medicine is shining a light on the gut microbiome and how microbiota dysbiosis may affect reproductive health and play a causal role in polycystic ovarian syndrome (PCOS) in women. PCOS is a common female endocrine disorder that affects 5-20% of reproductive-age women. Characterized by excess levels of androgen (“male” hormones), excess insulin, and low-grade inflammation, symptoms include infrequent or prolonged menstrual cycles, polycystic ovaries, and anovulatory infertility. While the exact causes of PCOS are unknown, the condition has a “substantial metabolic effect” that is associated with obesity, insulin resistance, and an increased risk of developing type 2 diabetes. In their 2019 Nature Medicine study, researchers analyzed the gut microbiota of 43 control subjects and 50 individuals with PCOS. While no significant differences were found in the bacterial alpha diversity between the groups, the bacterial beta diversity in the microbiomes of PCOS individuals were significantly decreased and found to have a more homogenous bacterial community than the control group. Most notably, however, was the finding of a marked increase of Bacteroides vulgatus in the gut microbiome of PCOS individuals compared to the healthy control group. To further investigate the role of B. vulgatus on gut microbiota, researchers administered the bacteria to mice, while maintaining a control mice group. Interestingly, the B. vulgatus-treated mice demonstrated PCOS-like symptoms of insulin resistance and ovarian dysfunction. Along with a disrupted estrous cycle, their ovaries showed increased cyst-like follicles; additionally, the mice treated with B. vulgatus produced fewer litter pups compared to the control group. In continuing their exploration of PCOS pathogenesis, researchers studied intestinal cytokines and discovered reduced interleukin-22 serum (IL-22) levels in both the treated mice and PCOS individuals compared to the control groups. Interleukins are proteins that regulate cell growth and play an important role in stimulating immune responses such as inflammation. To determine whether IL-22 could have a preventative or therapeutic role in PCOS, researchers administered the B. vulgatus-treated mice with IL-22. What they discovered was that IL-22 prevented PCOS manifestations and reduced insulin resistance along with “abnormal ovarian morphology induced by B. vulgatus,” citing the importance of IL-22’s anti-inflammatory role in PCOS pathogenesis. In conclusion, the authors point out that “modifying the gut microbiota, altering bile acid metabolism, and/or increasing IL-22 levels may be of value for the treatment of PCOS,” and that a deeper study of gut microbiota pathology is essential for understanding endocrine hormone dysregulation. In addition, a multidisciplinary approach incorporating lifestyle factors, nutritional assessment, and toxic exposure preventions may play a significant role towards improving metabolic, hormonal and reproductive health.
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Xinyu Qi, Chuyu Yun, Lulu Sun, Jialin Xia, Qing Wu, Ying Wang, Lina Wang, Yangming Zhang, Xianyi Liang, Liying Wang, Frank J Gonzalez, Andrew D Patterson, Huiying Liu, Liangshan Mu, Zehong Zhou, Yue Zhao, Rong Li, Ping Liu, Chao Zhong, Yanli Pang, Changtao Jiang, Jie Qiao
Nature Medicine, July 2019