Dataset Information

Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.

ABSTRACT: The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear. To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS. The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks. Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism. Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.

SUBMITTER: Yang YL

PROVIDER: S-EPMC8375444 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.

Yang Yue-Lian YL Zhou Wei-Wei WW Wu Shan S Tang Wen-Li WL Wang Zong-Wei ZW Zhou Zu-Yi ZY Li Ze-Wen ZW Huang Qing-Fa QF He Yan Y Zhou Hong-Wei HW

Endocrinology 20211001 10

<h4>Context</h4>The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear.<h4>Objective</h4>To assess the characteristics of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS.<h4>Setting and design</h4>The intestinal flo ...[more]

PMID: 34145455

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Project description:ObjectiveTo investigate the roles of fecal short-chain fatty acids (SCFAs) in polycystic ovary syndrome (PCOS).MethodsThe levels of SCFAs (acetate, propionate, and butyrate) in 83 patients with PCOS and 63 controls were measured, and their relationships with various metabolic parameters were analyzed. Intestinal microbiome analysis was conducted to identify relevant bacteria. The study took place at the Center for Reproductive Medicine at Shengjing Hospital of China Medical University in Shenyang, from 5 February to 23 May 2023. Logistic regression analyses were used to investigate the relationships between SCFAs, PCOS, and PCOS-related insulin resistance (IR). Differences in bacterial populations between women with PCOS-IR and those with PCOS-non-insulin resistance (NIR) were identified using linear discriminant analysis effect Size (LEfSe). The relationships between bacteria and fecal propionate levels were explored through linear regression analyses. The potential of fecal propionate and microbial profiles as biomarkers for insulin resistance in PCOS patients was assessed using receiver operating characteristic (ROC) curve analysis.ResultsHigher fecal propionate levels were observed in patients with PCOS compared to controls (p = 0.042) and in PCOS-IR compared to PCOS-NIR (p = 0.009). There was no significant difference in fecal propionate levels between the IR and NIR subgroups of women in the control group (p > 0.05). Additionally, higher fecal propionate levels were associated with IR in PCOS (p = 0.039; OR, 1.115; 95% CI, 1.006-1.237). The abundance of Prevotella copri and Megamonas funiformis was higher in PCOS-IR women compared to PCOS-NIR women (LDA score > 3) and correlated with fecal propionate levels (adjusted R² = 0.145, p < 0.001). The area under the curve (AUC) for propionate and the combined presence of P. copri and M. funiformis in predicting PCOS was 78.0%, with a sensitivity of 78.5% and a specificity of 72.4%. Pathways related to carbohydrate metabolism were significantly enriched in the microbiota of the PCOS-IR population but not in the control IR group.ConclusionsHigher fecal propionate levels correlate with PCOS-related insulin resistance. P. copri and M. funiformis might be key functional bacteria. Therefore, the combination of propionate levels and the abundance of these two bacteria may serve as a potential biomarker for insulin resistance in PCOS patients. Regulation of the intestinal microbiome might be beneficial for the metabolic health of women with PCOS.

Project description:ObjectiveTo examine the relation of menstrual cyclicity abnormalities to hyperandrogenism (HA) and dynamic state insulin resistance (IR) in oligo-ovulatory women with polycystic ovary syndrome (PCOS).DesignProspective cross-sectional study.SettingTertiary-care academic center.Patient(s)Fifty-seven women with PCOS (1990 National Institutes of Health criteria) and 57 healthy control women matched by body mass index (BMI).Intervention(s)Short insulin tolerance test (ITT).Main outcome measure(s)Menstrual cyclicity, sex hormone-binding globulin (SHBG), measures of HA (i.e., modified Ferriman-Gallwey score, total and free testosterone, dehydroepiandrosterone sulfate), and the rate constant for plasma glucose disappearance (kITT) derived from the short ITT.Result(s)Adjusting for age, BMI, and ethnicity, the mean androgen measures were higher and SHBG trended lower, kITT was lower, and the prevalence of IR was higher in PCOS than in controls, independent of menstrual cyclicity. The optimal cutoff point for IR was set at kITT value of 3.57%/minute or lower. Overall, 79% of the women with PCOS had IR. To control further for the effect of ethnicity, a subgroup of 46 non-Hispanic white PCOS participants were studied; those who exhibited amenorrhea (n = 15) or oligomenorrhea (n = 19) had or tended toward having a lower kITT and a higher prevalence of IR than the women with PCOS and oligo-ovulatory eumenorrhea (n = 12). The kITT trended lower and the prevalence of IR trended higher in women with PCOS and amenorrhea than those with oligomenorrhea. The measures of SHBG and HA were similar across the three menstrual groups.Conclusion(s)Oligo-ovulatory women with PCOS and overt oligo/amenorrhea have greater degrees of IR but not HA when compared with oligo-ovulatory eumenorrheic women with PCOS, suggesting that IR and hyperinsulinemia but not HA play a role in determining the degree of menstrual dysfunction, which can be used as a clinical marker for the degree of IR in oligo-ovulatory PCOS.

Dataset Information

Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.

Publications

Intestinal Flora is a Key Factor in Insulin Resistance and Contributes to the Development of Polycystic Ovary Syndrome.

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