Intersection of Polycystic Ovary Syndrome and the Gut Microbiome

Rizk, Maryan; Thackray, Varykina G.

doi:10.1210/jendso/bvaa177

Cited by 63 publications

(69 citation statements)

References 102 publications

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“…In support of these findings, ovariectomy increases weight gain in both STND- and HFD-fed rats and is associated with changes in gut microbiota [ 59 ]. Similarly, in a PCOS mouse model, FMT from androgen-treated mice disrupts metabolic and endocrine health in germ-free recipients, whereas gut microbiota from control donors protects against metabolic dysregulation [ 60 , 61 , 62 ]. In a different study, diet-independent, ovariectomy-induced weight gain was not rescued by cohousing with intact mice, with the goal of transferring of gut microbiota [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

et al. 2021

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A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

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Section: Discussionmentioning

confidence: 99%

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

et al. 2021

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“…Differences in the microbial community of adult patients with PCOS and healthy control, indicated by differences in βdiversity, have been identified in humans. 8,9,43,44 Adolescent girls (14-16 years old) with PCOS and obesity also showed differing βdiversity to girls with obesity but no PCOS. 45 In adult PNA rodents, the results of similar studies have been conflictingthere was no difference in PNA mice, whereas there was a difference in PNA rats.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies of the human gut microbiome have demonstrated lower αdiversity in premenopausal women with PCOS than in healthy women. 8,9,43,44 In addition, a recent study demonstrated that adolescent girls (14-16 years old) with PCOS and F I G U R E 1 1 Development of polycystic ovary syndrome (PCOS)-like phenotypes and changes in the gut microbiome in PNA offspring during their growth and development. A reproductive phenotype including disruption of the estrous cycle, histology typical of PCOS, and increased serum testosterone concentration were apparent at puberty in PNA female offspring.…”

Section: Discussionmentioning

confidence: 99%

Temporal relationship between alterations in the gut microbiome and the development of polycystic ovary syndrome‐like phenotypes in prenatally androgenized female mice

et al. 2021

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It has been recently recognized that prenatal androgen exposure is involved in the development of polycystic ovary syndrome (PCOS) in adulthood. In addition, the gut microbiome in adult patients and rodents with PCOS differs from that of healthy individuals. Moreover, recent studies have suggested that the gut microbiome may play a causative role in the pathogenesis of PCOS. We wondered whether prenatal androgen exposure induces gut microbial dysbiosis early in life and is associated with the development of PCOS in later life. To test this hypothesis, we studied the development of PCOS-like phenotypes in prenatally androgenized (PNA) female mice and compared the gut microbiome of PNA and control offspring from 4 to 16 weeks of age. PNA offspring showed a reproductive phenotype from 6 weeks and a metabolic phenotype from 12 weeks of age. The αdiversity of the gut microbiome of the PNA group was higher at 8 weeks and lower at 12 and 16 weeks of age, and the βdiversity differed from control at 8 weeks.However, a significant difference in the composition of gut microbiome between the PNA and control groups was already apparent at 4 weeks. Allobaculum and Roseburia were less abundant in PNA offspring, and may therefore be targets for future interventional studies. In conclusion, abnormalities in the gut microbiome appear as early as or even before PCOS-like phenotypes develop in PNA mice.Thus, the gut microbiome in early life is a potential target for the prevention of PCOS in later life. K E Y W O R D S androgens, delayed effects of prenatal exposure, gastrointestinal microbiome, polycystic ovary syndrome How to cite this article: Kusamoto A, Harada M, Azhary JMK, et al. Temporal relationship between alterations in the gut microbiome and the development of polycystic ovary syndrome-like phenotypes in prenatally androgenized female mice.

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“…( Hong et al., 2020 ) have discovered significant statistical differences in PCoA analysis of vaginal flora between PCOS and healthy people. However, there is also evidence suggesting that there is no statistically significant difference in beta diversity, for example, in intestinal flora and oral flora in PCOS patients ( Lindheim et al., 2016 ; Rizk and Thackray, 2021 ). This contradiction may exist for several reasons.…”

Section: Discussionmentioning

confidence: 99%

Changes in Vaginal Microbiome Diversity in Women With Polycystic Ovary Syndrome

Wang

Yang

et al. 2021

Front. Cell. Infect. Microbiol.

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Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women. It can be accompanied by many clinical manifestations that can vary between individuals. Previous studies have found that there are specific changes in the intestinal flora of PCOS patients, and interventions to modify the intestinal flora can significantly improve the symptoms of PCOS. Women with PCOS have a higher incidence of vaginitis compared to healthy women. Few studies to-date have focused on investigating vaginal flora. Here, we aimed to explore distribution changes of the vaginal microbiome in PCOS patients. We recruited 42 PCOS patients (T-PCOS) and 24 healthy controls (T-control). 16s rRNA gene sequencing was used to sequence their vaginal microbiome. Normally, Lactobacillus was dominated in vaginal. Lactobacillus-dominated-type vaginal microbiome in T-PCOS and T-control (L-PCOS and L-control) and non-Lactobacillus-dominated-type vaginal microbiome in T-PCOS and T-control (N-PCOS and N-control) were analyzed separately. A total of 655 operational taxonomic units were detected in this sequencing, including 306 unique to T-PCOS, 202 unique to T-control, and 147 common between the two groups. At the genus level, Lactobacillus accounted for more than 70% of the total microbiome. Observed species (P = 0.021), Chao1 index (P = 0.020), and ACE index (P = 0.023) decreased significantly in L-PCOS. Principal component analysis showed no statistically significant differences among the subgroups. There were significant statistical differences in principal coordinate analysis in the Jaccard distance between the T-PCOS and T-control groups and between the L-PCOS and L-control groups. Linear discriminant analysis effect size found that Enterococcus and Actinomycetes were significantly different in the T-PCOS group. Atopobium and Actinomyces were statistically significantly different in patients with L-PCOS and N-PCOS group, respectively. Environmental factor analysis found that Ezakiella was significantly negatively correlated with age, while Streptococcus was significantly negatively correlated with follicle stimulating hormone. There were statistically significant differences between PCOS patients and healthy women in the vaginal microbiome, regardless of the abundance of Lactobacillus. Alpha diversity of vaginal microbiome decreased markedly in PCOS patients when it was dominated by Lactobacillus spp. Actinomyces could be a potential biomarker to identify PCOS. Streptococcus may have an impact on the pathological changes in PCOS by affecting the female reproductive endocrine environment.

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Intersection of Polycystic Ovary Syndrome and the Gut Microbiome

Cited by 63 publications

References 102 publications

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Temporal relationship between alterations in the gut microbiome and the development of polycystic ovary syndrome‐like phenotypes in prenatally androgenized female mice

Changes in Vaginal Microbiome Diversity in Women With Polycystic Ovary Syndrome

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