Dataset Information

Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism.

ABSTRACT: Context:A majority of women with polycystic ovary syndrome (PCOS) have metabolic abnormalities that result in an increased risk of developing type 2 diabetes and heart disease. Correlative studies have shown an association between changes in the gut microbiome and metabolic disorders. Two recent studies reported a decrease in ? diversity of the gut microbiome in women with PCOS compared with healthy women. Objective:We investigated whether changes in the gut microbiome correlated with specific clinical parameters in women with PCOS compared with healthy women. We also investigated whether there were changes in the gut microbiome in women with polycystic ovarian morphology (PCOM) who lacked the other diagnostic criteria of PCOS. Participants:Subjects were recruited at the Poznan University of Medical Sciences. Fecal microbial diversity profiles of healthy women (n = 48), women with PCOM (n = 42), and women diagnosed with PCOS using the Rotterdam criteria (n = 73) were analyzed using 16S ribosomal RNA gene sequencing. Results:Lower ? diversity was observed in women with PCOS compared with healthy women. Women with PCOM had a change in ? diversity that was intermediate between that of the other two groups. Regression analyses showed that hyperandrogenism, total testosterone, and hirsutism were negatively correlated with ? diversity. Permutational multivariate analysis of variance in UniFrac distances showed that hyperandrogenism was also correlated with ? diversity. A random forest identified bacteria that discriminated between healthy women and women with PCOS. Conclusion:These results suggest that hyperandrogenism may play a critical role in altering the gut microbiome in women with PCOS.

SUBMITTER: Torres PJ

PROVIDER: S-EPMC6276580 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism.

Torres Pedro J PJ Siakowska Martyna M Banaszewska Beata B Pawelczyk Leszek L Duleba Antoni J AJ Kelley Scott T ST Thackray Varykina G VG

The Journal of clinical endocrinology and metabolism 20180401 4

<h4>Context</h4>A majority of women with polycystic ovary syndrome (PCOS) have metabolic abnormalities that result in an increased risk of developing type 2 diabetes and heart disease. Correlative studies have shown an association between changes in the gut microbiome and metabolic disorders. Two recent studies reported a decrease in α diversity of the gut microbiome in women with PCOS compared with healthy women.<h4>Objective</h4>We investigated whether changes in the gut microbiome correlated ...[more]

PMID: 29370410

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Project description:ContextAndrogen excess may be adrenal and/or ovarian in origin; we hypothesized that a subgroup of patients with polycystic ovarian syndrome (PCOS) may have some degree of abnormal adrenocortical function.ObjectiveThe objective of the study was to evaluate the pituitary adrenal axis with an oral low- and high-dose dexamethasone-suppression test (Liddle's test) in women with PCOS.DesignThis was a case-control study.SettingThe study was conducted at the National Institutes of Health Clinical Center.ParticipantsA total of 38 women with PCOS and 20 healthy volunteers (HV) aged 16-29 years participated in the study.Main outcome measuresUrinary free cortisol (UFC) and 17-hydroxysteroids (17OHS) before and after low- and high-dose dexamethasone and assessment of adrenal volume by computed tomography scan were measured.ResultsTwenty-four-hour urinary 17OHS and UFC were measured during day 1 to day 6 of the Liddle's test. Baseline UFC levels were not different between PCOS and HVs; on the day after the completion of high-dose dexamethasone administration (d 6), UFC was higher in the PCOS group (2.0 ± 0.7 μg/m(2)·d) than the HV group (1.5 ± 0.5) (P = .038). On day 5, 17OHS and UFC were negatively correlated with adrenal volumes (left side, rp = -0.47, P = .009, and rp = -0.61, P < .001, respectively). PCOS patients above the 75th percentile for UFC and/or 17OHS after high-dose dexamethasone (n = 15) had a significantly smaller total adrenal volume (6.9 ± 1.9 cm(3) vs 9.2 ± 1.8 cm(3), P = .003) when compared with the remaining PCOS patients (n = 22), but they did not have worse insulin resistance or hyperandrogenism.ConclusionsIn a subset of young women with PCOS, we detected a pattern of glucocorticoid secretion that mimicked that of patients with micronodular adrenocortical hyperplasia: they had smaller adrenal volumes and higher steroid hormone secretion after dexamethasone compared with the group of PCOS with appropriate response to dexamethasone.

Project description: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.

Project description:Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.

Dataset Information

Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism.

Publications

Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism.

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