Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder in reproductive-age women, which also negatively perturbs person's psychiatric health. Herein, we investigated the effect of oxyberberine on PCOS- and depression-like phenotypes in female Sprague-Dawley rats. To generate PCOS- and depression-like phenotypes, rats were injected with letrozole (1 mg/kg/day for 21 days) and exposed to 14 days of chronic-unpredictable mild stress (CUMS). We synthesized oxyberberine from its natural parent phytoconstituent i.e., berberine. Rats underwent letrozole + CUMS exposure displayed an increased number of neutrophils in a vaginal smear test indicating a PCOS-like phenotype (i.e., disrupted estrus cycle). Moreover, these rats also showed anhedonia-, depression-, and anxiety-like behaviors in the sucrose-preference test, forced-swimming test, and elevated plus-maze test. Peroral administration of oxyberberine for 21 days, at 50 and 100 mg/kg doses, reversed letrozole + CUMS generated perturbations in rats. The total exploratory behavior in the open field test remained unaffected across the treatment groups. Oxyberberine treatment also restored the organ-weight index of the ovary and uterus and follicular development of the ovary. Systemic and uterine levels of oxyberberine were found to be 0.17-0.80 ng/mL and 1.03-3.62 ng/mL, respectively measured using a liquid chromatography-mass spectrometry assay. Oxyberberine also positively modulated the levels of catalase and malondialdehyde in intestine and spleen, and testosterone and luteinizing hormones in the systematic circulation and CYP17A1, CYP19A1, and SHBG expression in the ovary. These results suggest that oxyberberine improves PCOS- and depression-like phenotypes in rats by modulating testosterone hormone, CYP17A1, CYP19A1, and SHBG enzyme expression in the ovary.

Intestinal health issues affect approximately 20% of the global population, yet the relationship between insulin resistance (IR) and intestinal health remains poorly understood. This study evaluated the discriminative ability of five IR surrogate indices-homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride-glucose index (TyG), TyG adjusted for body mass index (TyG-BMI), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), and estimated glucose disposal rate (eGDR)-for chronic diarrhea and constipation in adults.

Using data from the 2005-2010 National Health and Nutrition Examination Survey (NHANES), we analyzed associations between five IR surrogate indices and chronic diarrhea/constipation in adults. Key variables were selected via the Boruta algorithm and incorporated into weighted multivariate logistic regression models. Restricted cubic spline (RCS) analysis, threshold effect analysis, and receiver operating characteristic (ROC) curves were employed to assess these associations.

Among 6,133 participants in this study, 7.5% had chronic diarrhea and 7.4% had chronic constipation. After adjusting for confounders, multivariate logistic regression revealed significant positive associations of HOMA-IR (OR: 1.02, 95% CI: 1.00-1.04), TyG (OR: 1.28, 95% CI: 1.05-1.55), and TyG-BMI (OR: 1.01, 95% CI: 1.00-1.01) with chronic diarrhea, while eGDR showed an inverse association (OR: 0.88, 95% CI: 0.80-0.96). No significant associations were observed between IR surrogate indices and chronic constipation. RCS and threshold effect analyses demonstrated a non-linear relationship between TG/HDL-C and chronic diarrhea: Each 1-unit increase in TG/HDL-C below the threshold of 7.33 elevated diarrhea risk by 11% (95% CI: 1.05-1.17). ROC analysis indicated that TyG-BMI (AUC: 0.656 vs. 0.644) and eGDR (AUC: 0.652 vs. 0.644) significantly improved the discriminative ability of the baseline model for chronic diarrhea, whereas HOMA-IR and TyG showed no statistically meaningful enhancements.

IR surrogate indices were significantly associated with chronic diarrhea but not chronic constipation, highlighting their potential as biomarkers for screening diarrhea in the general population.

Triclosan (TCS), a typical endocrine disruptor, is widely used as an antibacterial agent in consumer goods. However, there are few studies on the effects of long-term low-dose TCS exposure on ovarian function in F1 female mice. In this paper, F1 female mice were exposed to TCS (0-3000 μg/kg/day) from intrauterine to postnatal day (PND) 91 to investigate its effects on the ovary. The results revealed that the number of total follicles was decreased, while atretic follicles was increased after TCS exposure. At the hormonal level, the secretion of estradiol was reduced, while follicle-stimulating hormone and luteinizing hormone were increased after TCS exposure. Observation of vaginal smear showed that TCS disrupted the estrous cycle of F1 female mice, especially at the dose of 3000 μg/kg/day. Moreover, TCS promoted cell apoptosis by activating the p38-MAPK signaling pathway and oxidative stress in vitro. In addition, analysis of the fecal microbiome and serum metabolomics revealed that exposure to TCS may cause gut microbiota disruption and metabolic abnormalities in F1 female mice. In conclusion, long-term low-dose TCS exposure may induce primary ovarian insufficiency phenotype in F1 female mice via inducing cell apoptosis and disrupting gut microbiota and metabolism.

Osteoporosis is a multifactorial bone metabolic disorder characterized by the deterioration of bone mass and microarchitecture, leading to increased fragility and fracture risk. Recent advances have revealed the critical role of the gut microbiota in the pathogenesis of osteoporosis, primarily mediated by metabolite-driven and immune-mediated interactions along the gut-bone axis. Dysbiosis, or microbial imbalance, can influence bone health by modulating host metabolism, immune function, and endocrine responses. While growing evidence suggests that gut microbiota modulation holds therapeutic potential for osteoporosis, the underlying mechanisms remain poorly understood. This review examines the latest findings on the role of prebiotics, probiotics, and natural bioactive substances in modulating the gut microbiota to improve bone health. We discuss how these interventions may restore microbial balance, enhance gut barrier function, and reduce systemic inflammation, thereby influencing bone metabolism. A deeper understanding of the gut-bone axis will pave the way for more targeted, effective, and personalized therapeutic strategies for osteoporosis prevention and treatment.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.

PCOS is an endocrine disorder that affects women of reproductive age. The root of PCOS is ovarian dysfunction, which presents as hormonal disturbances affecting normal ovarian function to cause the symptoms and complications of the disease. This dysfunction causes symptoms like impaired maturation of follicles and disorders of various origins with multiple treatment regimens that are not always clear. Therefore, the present review mainly concentrates on the genetic level of ovarian dysfunction of PCOS. The articles were identified through a vigorous literature search where search engines such as PubMed, Google Scholar, databases, and Science Direct were used, and the articles published from 2015 to 2025 were referred. We identified that the key genes involved in the ovarian dysfunctions in PCOS include CYP11A1, CYP17A1, CYP19A1, AR, FSHR, LHCGR, AMH, INSR, SHBG, IRS1, GATA4, ADIPOQ, YAP1, TCF7L2, and DENND1A, which play a role in gonadotropin action, steroidogenesis, and folliculogenesis. Furthermore, epigenetic factors and miRNAs miR-93, 222, 155, 146a, 132, 320, 27a, 483, 21, 378, 17-92 Cluster, and 375, 221 are also involved in it. Abnormal expression of these genes is known to play a critical role in the etiology and pathogenesis of PCOS. Present treatment includes the use of oral contraceptives, anti-androgen agents, insulin-sensitizing agents, and ovulation-inducing agents, and future treatment may consist of miRNA therapy, drug repositioning, and genetic markers that might be used for early identification and better management of ovarian dysfunction. Thus, the current review discusses ovarian dysfunction in PCOS, the involvement of potential genes and epigenetic factors, and miRNAs concerning ovulation and its therapeutic implications.

Polycystic ovarian syndrome (PCOS) is one of the chief causes of infertility in women of reproductive age. Several drugs belonging to the oral contraceptive class have been approved for the treatment of PCOS. Nonetheless, the capability to target only a few symptoms of PCOS and fatal side effects are key hurdles to their use. Therefore, repurposing existing drugs can be promising in managing PCOS efficiently. Drugs from different pharmacological classes like antidiabetics (metformin, rosiglitazone, pioglitazone, and semaglutide), statins (simvastatin and atorvastatin), antiandrogen drugs (finasteride and flutamide), etc. demonstrated significant potential in managing PCOS. The present review offers a comprehensive overview of all the medications examined as potential repurposed options for the efficient treatment of PCOS. The pathogenesis of PCOS, existing therapies for PCOS and their challenges, drug repurposing and its significance is also explained. The small-molecular drugs from various pharmacological classes and different phytoceuticals repurposed against PCOS are discussed along with their anti-PCOS activity mechanisms. Moreover, novel drug targets responsible for PCOS and opportunities for drug repurposing are briefed. The repurposed drugs in clinical trials for PCOS and drug repurposing challenges are discussed. Thus, drug repurposing can serve as a potential way to effectively treat PCOS, reducing the extent of infertility and improving the quality of life of women.

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (Allmania nodiflora) were assessed, with metformin as the standard. GD dams exhibited weight and glucose reduction, pancreatic IL-6 elevation, GLUT3 reduction, astroglia changes in the cerebral cortex, gut barrier impairment, cognitive impairment, and heightened anxiety compared to controls. Bacterial 16s rRNA sequencing revealed dysbiosis, with reduced Erysipelotrichales in GD dams compared to controls. Metformin lowered blood glucose levels but failed to rescue functional and behavioral phenotypes in both GD dams and offspring. Phytocompound treatment improved blood glucose, reduced pancreatic inflammation, improved gut barrier integrity, reversed dysbiosis, and enhanced brain health. It rescued behavioral deficits and improved cognitive outcomes in offspring, suggesting the prebiotic phytocompound may be a more effective therapeutic agent for GD in humans.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting reproductive-age women, characterized primarily by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. In recent years, the gut microbiota has garnered widespread attention for its potential role as a key regulator of host metabolism in the pathogenesis of PCOS. Studies have shown that PCOS patients exhibit dysbiosis in their gut microbiota, characterized by reduced microbial diversity, an imbalance in the ratio of Firmicutes to Bacteroidetes, changes in the abundance of specific taxa, and abnormal levels of metabolic products. These alterations may exacerbate metabolic dysfunction in PCOS through multiple mechanisms, including influencing host energy metabolism, disrupting lipid and bile acid metabolism, and inducing chronic inflammation. Addressing gut dysbiosis through the modulation of patients' microbiomes-such the use of, prebiotics, fecal microbiota transplantation, and optimizing diet lifestyle-may offer strategies for improving metabolic abnormalities and alleviating clinical symptoms in PCOS. Additionally, the gut microbiome promises as a potential marker, aiding in the precise diagnosis and personalization of PCOS. Although our current understanding of how the gut microbiota influences PCOS is still limited, research is needed to explore the causal relationships and mechanisms involved, providing a more reliable theoretical basis for clinical. This review aims summarize the research progress on the relationship between gut microbiota and PCOS, and to suggest future directions to promote the development of prevention and treatment strategies for PCOS.

Polycystic Ovarian Syndrome is one of the major prevalent causes of infertility reported worldwide nearly 6-26 %, especially in girls hitting puberty and women at their childbearing age. The main clinical manifestations include irregular menstrual cycle, small cysts on one or both ovaries, chronic oligo-anovulation, and hirsutism. The etiological criteria are very complex and related to many factors like obesity, insulin sensitivity, inflammation, hyperandrogenism, diabetes mellitus type II, cardiovascular diseases, and dysbiosis of gut microbiota. The given review focuses on managing PCOS through probiotics by analyzing the effects on the symptoms of the disease. The probiotics effective in treating PCOS belong to Bifidobacterium, Lactobacilli, Clostridium, Enterococcus, and other Lactic acid bacteria. Its significance in PCOS is mainly due to the antagonizing of the growth of pathogenic microorganisms, increasing intestinal mucus layer production, reducing intestinal permeability, and modulating the gastrointestinal immune system. Also, their interaction with certain hormones such as insulin, androgen, and estrogen through short-chain fatty acids influences fertility. More research is necessary to validate these results. Probiotic supplements could be a viable option for treating PCOS in adults.

Introduction: Insulin resistance (IR) is a highly prevalent pathophysiological entity implicated in the development of a wide variety of metabolic, cardiovascular, and endocrine disorders. The aim of this study is to assess the association between sociodemographic variables and healthy habits with IR risk scales. Methodology: This dual study, incorporating both longitudinal-retrospective and cross-sectional designs, analyzed healthcare workers across four professional categories (physicians, nurses, healthcare technicians, and auxiliary personnel). It examined the association of age, sex, professional category, smoking status, physical activity, and adherence to the Mediterranean diet with elevated scores on insulin resistance risk scales. Results: All the variables analyzed were associated with the presence of elevated values of the IR scales, with age, sex, and physical activity showing the strongest association (reflected in the odds ratio values). Conclusions: The profile of an individual with a higher risk of presenting elevated values of the IR risk scales would be an elderly male auxiliary health worker who is a smoker and is physically inactive, with a low adherence to the Mediterranean diet.

Polycystic ovary syndrome (PCOS) is a prevalent disorder of the endocrine system with significant clinical implications, often leading to health complications related to adipose tissue accumulation, including obesity, insulin resistance (IR), metabolic syndrome, and type 2 diabetes mellitus. While the precise pathogenesis of PCOS remains unclear, it is now recognized that genetic, endocrine, and metabolic dysregulations all contribute significantly to its onset. The immunopathogenesis of PCOS has not been extensively explored, but there is growing speculation that immune system abnormalities may play a pivotal role. This chronic inflammatory state is exacerbated by factors such as obesity and hyperinsulinemia. Therefore, this review aims to elucidate the interplay between IR in PCOS patients, the controlled immune response orchestrated by immune cells and immunomodulatory molecules, and their interactions with adipocytes, hyperandrogenemia, chronic inflammation, and metabolic homeostasis.

Metabolic syndrome is a metabolic disorder characterized by hypertension, dyslipidemia, impaired glucose tolerance, and abdominal obesity. Impaired insulin action or insulin resistance initiates metabolic syndrome. The prevalence of insulin resistance is increasing all over the world. Insulin resistance results in the defective metabolism of carbohydrates and lipids, in addition to low-grade chronic inflammation. Insulin resistance is associated with metabolic syndrome, which is a risk factor for a number of pathological conditions, such as Type 2 diabetes (T2D), cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and polycystic ovarian syndrome (PCOS). Genome-wide association studies have increased our understanding of many loci linked to these diseases and others. In this review, we discuss insulin resistance and its contribution to metabolic syndrome and these diseases. We also discuss the genetic loci associated with them. Genetic testing is invaluable in the identification and stratification of susceptible populations and/or individuals. After susceptible individuals and/or populations have been identified via genetic testing or screening, lifestyle modifications such as regular exercise, weight loss, a healthy diet, and smoking cessation can reduce or prevent metabolic syndrome and its associated pathologies.

Experimental and clinical studies have suggested that symbiotics might effectively manage type 2 diabetes mellitus (T2DM) by modulating the intestinal microbiota. However, these studies' limited sources, small sample sizes, and varied study designs have led to inconsistent outcomes regarding glycaemic control. This study aimed to investigate the effects of symbiotics on the anthropometric measures, glycaemic control, and lipid profiles of patients with T2DM.

A double-blind, placebo-controlled, parallel clinical trial was conducted at two diabetes outpatient clinics. The main researcher and participants were blinded to the capsule content throughout the study. Sixty-six patients with T2DM aged 30-75 years were randomly allocated, using even and odd numbers, into two equal groups. These groups received either symbiotic capsules containing 200 million colony-forming units plus fructo-oligosaccharide or a placebo for 12 weeks. The primary objective was a decrement in glycated haemoglobin [HbA1c]. The patients' anthropometric measures, fasting blood sugar, high-density lipoprotein [HDL], low-density lipoprotein [LDL], total serum cholesterol and serum triglyceride levels were also assessed at baseline and after 12 weeks of intervention. Non-parametric tests were used for statistical analyses.

Within-group analysis revealed significant decreases in body mass index (BMI) and waist circumference (P = 0.005 and 0.023, respectively) and a significant increase in HDL levels in the symbiotic group (P = 0.04). HbA1c levels significantly increased in the placebo group (P = 0.016) but were not significantly reduced in the symbiotic group. The between-group analysis revealed significantly lower fasting blood sugar (FBS) levels in the symbiotic group, and higher in the placebo group (P = 0.02). No significant changes existed in total serum cholesterol, LDL, and triglyceride levels in either the symbiotic or placebo group.

Symbiotics improve BMI, waist circumference, HDL, and FBS levels and prevent the worsening of HbA1c levels in patients with T2DM. Our preliminary results indicate the potential benefits of symbiotics in patients with T2DM, which may lead to better diabetes control. However, this evidence requires further assessment in larger trials.

The trial was registered retrospectively at the International Standard Registered Clinical/Social Study Number Registry (ISRCTN34652973) on 05/01/2024.

To investigate composition of gut microbial community in a rat model of functional dyspepsia (FD) and to explore the interventional effects of Simo Tang (, SMT).

A rat model of FD was established through the tail-clamping stimulation method. The rat model of FD was assessed by the state of rats, their weight, sucrose preference rate, and intestinal propulsion rate. The DNA was extracted from stool samples after treatment with SMT. Amplified polymerase chain reaction (PCR) products of the 16S rDNA were sequenced using NovaseQ6000 after construction of libraries. Composition of gut microbial community in the stool samples was determined and analyzed by cluster analysis, bioinformatic analysis, and analysis of α-diversity and β-diversity.

The rat model of FD was successfully established using the tail-clamping stimulation method. The statistical results of cluster analysis of operational taxonomic units (OTUs) showed that the relative abundance of OTUs in the FD group was the lowest, while it was the highest in the normal (N) group. The composition of microbiome in the four groups was similar at phyla level. Compared with the FD group, the abundance of Firmicutes was downregulated, and the abundance of Proteobacteria and Bacteroidetes was upregulated in the Simo Tang (SMT) and high-dose Simo Tang (SMT.G) groups. The ratio of Bacteroidetes/ Firmicutes was also elevated. According to the analysis of α-diversity and β-diversity, the abundance of flora in FD rats was significantly reduced. The treatment using SMT appeared beneficial to improve the diversity of flora. SMT could improve the intestinal flora in FD rats. The results showed that FD rats had intestinal flora imbalance, and species diversity increased. The results suggested that SMT could regulate the disorders of intestinal flora caused by FD.

SMT could restore gut homeostasis and maintain gut flora diversity by modulating the gut microbiota and its associated metabolites in rats, thereby treating gastrointestinal diseases.

Direct and indirect evidence suggests that endometrial receptivity may play a crucial role in the reduced fertility rate of women with polycystic ovary syndrome (PCOS). Various pharmacological and non-pharmacological strategies with potential effects on endometrial receptivity in patients with PCOS have been proposed. The aim of this study was to summarize the rationale and the clinical and experimental evidence of interventions tested for improving endometrial receptivity in infertile patients with PCOS. A systematic review was conducted by consulting electronic databases. All interventions with a potential influence on endometrial receptivity in infertile patients with PCOS were evaluated, and their main biological mechanisms were analysed. In total, 24 interventions related to endometrial receptivity were identified. Notwithstanding a strong biological rationale, no intervention aimed at improving endometrial receptivity in women with PCOS is supported by an adequate body of evidence, limiting their use in clinical practice. Further high-quality research is needed in this field to limit potentially ineffective and unsafe add-on treatments in infertile patients with PCOS.

Depression is one of the complications in patients with polycystic ovary syndrome (PCOS) that leads to considerable mental health. Accumulating evidence suggests that human gut microbiomes are associated with the progression of PCOS and depression. However, whether microbiota influences depression development in PCOS patients is still uncharacterized. In this study, we employed metagenomic sequencing and transcriptome sequencing (RNA-seq) to profile the composition of the fecal microbiota and gene expression of peripheral blood mononuclear cells in depressed women with PCOS (PCOS-DP, n = 27) in comparison to mentally healthy women with PCOS (PCOS, n = 18) and compared with healthy control (HC, n = 27) and patients with major depressive disorder (MDD, n = 29). Gut microbiota assessment revealed distinct patterns in the relative abundance in the PCOS-DP compared to HC, MDD, and PCOS groups. Several gut microbes exhibited uniquely and significantly higher abundance in the PCOS-DP compared to PCOS patients, inducing EC Ruminococcus torques, Coprococcus comes, Megasphaera elsdenii, Acidaminococcus intestini, and Barnesiella viscericola. Bacteroides eggerthii was a potential gut microbial biomarker for the PCOS-DP. RNA-seq profiling identified that 35 and 37 genes were significantly elevated and downregulated in the PCOS-DP, respectively. The enhanced differential expressed genes (DEGs) in the PCOS-DP were enriched in pathways involved in signal transduction and endocrine and metabolic diseases, whereas several lipid metabolism pathways were downregulated. Intriguingly, genes correlated with the gut microbiota were found to be significantly enriched in pathways of neurodegenerative diseases and the immune system, suggesting that changes in the microbiota may have a systemic impact on the expression of neurodegenerative diseases and immune genes. Gut microbe-related DEGs of CREB3L3 and CCDC173 were possible molecular biomarkers and therapeutic targets of women with PCOS-DP. Our multi-omics data indicate shifts in the gut microbiome and host gene regulation in PCOS patients with depression, which is of possible etiological and diagnostic importance.

Over the past decade, research on the human microbiota has become a hot topic. Among them, the female reproductive tract (FRT) also has a specific microbiota that maintains the body's health and dynamic balance, especially in the reproductive aspect. When the FRT ecosystem is dysregulated, changes in immune and metabolic signals can lead to pathological and physiological changes such as chronic inflammation, epithelial barrier disruption, changes in cell proliferation and apoptosis, and dysregulation of angiogenesis and metabolism, thereby causing disruption of the female endocrine system. Premature ovarian insufficiency (POI), a clinical syndrome of ovarian dysfunction, is primarily influenced by immune, genetic, and environmental factors. New evidence suggests that dysbiosis of the FRT microbiota and/or the presence of specific bacteria may contribute to the occurrence and progression of POI. This influence occurs through both direct and indirect mechanisms, including the regulation of estrogen metabolism. The use of probiotics or microbiota transplantation to regulate the microbiome has also been proven to be beneficial in improving ovarian function and the quality of life in women with premature aging. This article provides an overview of the interrelationships and roles between the FRT microbiome and POI in recent years, to fully understand the risk factors affecting female reproductive health, and to offer insights for the future diagnosis, treatment, and application of the FRT microbiome in POI patients.

Polycystic ovary syndrome (PCOS), a common endocrine disorder, affects women of reproductive age, and its adverse consequences affect women throughout their lifespan, from adolescence to postmenopause. The prevalence of depression is much higher in women with PCOS than in healthy controls. Thus, it is recommended that depressive syndrome be screened routinely in all patients with PCOS at diagnosis. To date, no comprehensive bibliometric analysis has been conducted in this field. Therefore, we conducted a bibliometric analysis to describe the current status, trends, and hotspots of PCOS research related to depression.

Using data retrieved from the Web of Science (WoS) Core Collection database from 1993 to 2024, bibliometric analyses were performed using WoS and CiteSpace software.

Since the first paper was published in 1993, studies related to PCOS and depression have remained rare in the following decade. Since the establishment of the Rotterdam criteria in 2003, research on the etiology, pathogenesis, and treatment of PCOS with depressive syndrome has entered a booming period. The United States and Australia indisputably took leading positions in this area, with the most outstanding institutions in the world being the University of Pennsylvania and Monash University. Although achievements have flourished since 2003, the exact pathogenesis of PCOS remains uncertain owing to its heterogeneity. New research is rapidly increasing to fill these gaps and to push forward the goal of improving the quality of life in women with PCOS and depression. Along with progress in research, the world's leading societies organize conferences every 5 years to update guidelines for the assessment and management of PCOS. "Oxidative stress," "inflammation," "obstructive sleep apnea," "gut microbiota," and "single nucleotide polymorphism" appeared as new hotspots in the recent 5 years.

A bibliometric analysis was performed to describe the trends and hotspots of research in women with PCOS and depression to attract the attention of more researchers to this topic.

https://www.webofscience.com/wos/woscc/basic-search.

Background/Objectives: Polycystic ovary syndrome is a common endocrine disorder in women of reproductive age characterized by insulin resistance and hormonal imbalances. Recent research suggests that probiotics and synbiotics may improve these parameters by modulating the gut microbiota. This study systematically reviewed randomized clinical trials evaluating the impact of probiotic, prebiotic, and synbiotic supplementation on insulin resistance and hormonal parameters in women with PCOS. Methods: Exhaustive searches were conducted in PubMed, Cochrane CENTRAL, Scopus, Web of Science, and Embase, following PRISMA guidelines. Randomized trials assessing supplementation with probiotics, prebiotics, or synbiotics for at least 8 weeks in women diagnosed with PCOS according to the Rotterdam criteria were included. Data on participants, interventions, and outcomes related to insulin resistance and hormones were extracted. Results: Eleven studies from Iran involving overweight or obese women aged 15 to 48 were included. Probiotic and synbiotic supplementation showed significant improvements in insulin resistance (reductions in HOMA-IR, fasting glucose, and insulin), lipid profiles (decreased LDL and triglycerides; increased HDL), and hormonal balance (increased SHBG, decreased total testosterone). Synbiotics had more pronounced effects than probiotics or prebiotics alone. Adherence was high, and side effects were minimal. Conclusions: Despite promising results, limitations such as small sample sizes, homogeneous populations, and short intervention durations limit the generalization of the findings. Larger, longer, multicenter trials with diverse populations and standardized methodologies are needed to confirm the efficacy and safety of synbiotics in managing PCOS. Integrating these interventions could improve clinical management and quality of life for affected women, but additional evidence is required to support widespread use.

Insulin resistance (IR) can lead to infertility in women. The primary objective of this research was to examine how estimated glucose disposal rate (eGDR) correlates with infertility in women, assessing its validity as an indicator of IR.

Data from the National Health and Nutrition Examination Survey spanning 2013 to 2018 were analyzed in this study. In order to investigate the correlation between eGDR and the prevalence of female infertility, this study used a combination of weighted multivariate regression analysis, restricted cubic spline (RCS) analysis, subgroup analyses, sensitive analysis, and receiver operating characteristic (ROC) curves.

This study enrolled 2541 women, with an average age of (32.52 ± 0.23) years. The overall infertility rate was 14.27%. A negative relationship was observed between eGDR levels and female infertility. Each increment of one unit in eGDR was linked to a 14% reduction in infertility incidence (OR = 0.86, 95% CI 0.80-0.94). RCS analysis revealed a nonlinear, inverse correlation between eGDR and female infertility. Subgroup analyses indicated that age influenced the association between eGDR and female infertility. The ROC curve suggested that eGDR was significantly better than HOMA-IR in predicting infertility [eGDR: 0.632 (95% CI: 0.603, 0.660) vs. HOMA-IR: 0.543 (95% CI: 0.514, 0.572)].

There was an observed association where lower eGDR levels were linked with higher rates of female infertility. These results emphasize the significance of implementing measures to manage IR to protect women's reproductive health.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems, often resulting in infertility, obesity, insulin resistance, and cardiovascular complications. The aim of this study is to investigate the role of intestinal flora and its metabolites, particularly short-chain fatty acids (SCFAs), in the development of PCOS, and to assess the effects of metformin therapy on these components. SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. Fecal microbiota were quantitatively detected by real-time polymerase chain reaction (PCR). To assess the efficacy of six months of metformin treatment, changes in the microbiota and SCFAs in the PCOS group (n=69) were also evaluated. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria (namely, the C. leptum group and Prevotella spp.) alongside a notable overgrowth of opportunistic microorganisms (C. perfringens, C. difficile, Staphylococcus spp., and Streptococcus spp.). An overproduction of acetic acid (AA, FC=0.47, p<0.05) and valeric acid (VA, FC=0.54, p<0.05) suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (r=-0.33, p=0.02), insulin resistance (r=-0.39, p=0.02), and chronic inflammation. Although serum SCFA levels showed non-significant changes following metformin treatment (p>0.05), the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Insulin resistance (IR) is one of the major complications of polycystic ovary syndrome (PCOS). This study aimed to investigate the effects and the molecular regulatory mechanism by which Dendrobium nobile-derived polysaccharides (DNP) improve IR in rats with letrozole and high-fat-diet induced PCOS. In vivo, DNP (200 mg/kg/d) administration not only reduced body weight, blood glucose, and insulin levels in PCOS rats, but also improve the disrupted estrous cycle. In addition, DNP treatment reduced atretic and cystic follicles and enhanced granulosa cell layer thickness, thereby restoring follicle development. In vitro, DNP treatment (100 μM) increased lactate levels and decreased pyruvate levels in insulin-treated (8 μg/mL) KGN cells. Additionally, DNP also decreased the expression of IGF1 and increased that of IGF1R, SIRT2, LDHA, PKM2 and HK2 both in vivo and in vitro. Also, SIRT2 expression was specifically inhibited by AGK2, while DNP significantly improved IR and glycolysis by reversing the effect of AGK2 treatment on lactate and pyruvate production, upregulating the expression levels of IGF1R, LDHA, HK2, and PKM2 and downregulating the expression level of IGF1. The results indicate that DNP can effectively improve IR and restore glycolytic pathway by activating SIRT2, which may provide a potential therapeutic approach for PCOS patients.

Infertility is a disease of impaired fertility. With socioeconomic development, changes in human lifestyles, and increased environmental pollution, the problem of low human fertility has become increasingly prominent. The incidence of global infertility is increasing every year. Many factors lead to infertility, and common female factors include tubal factors, ovulation disorders, endometriosis, and immune factors. The gut microbiota is involved in many physiological processes, such as nutrient absorption, intestinal mucosal growth, glycolipid metabolism, and immune system regulation. An altered gut flora is associated with female infertility disorders such as polycystic ovary syndrome (PCOS), endometriosis (EMs), and premature ovarian failure (POF). Dysbiosis of the gut microbiota directly or indirectly contributes to the development of female infertility disorders, which also affect the homeostasis of the gut microbiota. Identifying the etiology and pathogenesis of infertility in patients is the focus of reproductive medicine physicians. We studied the developmental mechanism between the gut microbiota and PCOS, EMs, and POF from a new perspective, providing new ideas for diagnosing and treating female infertility diseases and specific reference values for eugenics.

Polycystic ovary syndrome (PCOS), a common endocrine disorder in women of reproductive age, is closely associated with chronic low-grade inflammation and metabolic disturbances. In PCOS mice, dietary inulin has been demonstrated to regulate intestinal flora and inflammation. However, the efficacy of dietary inulin in clinical PCOS remains unclear.

The intestinal flora and related metabolic indexes of obese patients with polycystic ovary syndrome (PCOS) after 3 months of inulin treatment were analyzed.

To analyze the intestinal flora and related metabolic indexes in healthy controls and obese patients with polycystic ovary syndrome after 3 months of inulin treatment.

The results showed that dietary inulin improved sex hormone disorders, reduced BMI and WHR levels in obese women with PCOS. In addition, the inulin intervention reduced plasma TNF-α, IL-1β, IL-6, and MCP-1levels. Inulin intervention increased the abundance of Actinobacteria, Fusobacteria, Lachnospira, and Bifidobacterium, as well as decreased the ratio of F/B and the abundance of proteobacteria, Sutterella, and Enterobacter. Correlation analyses showed a strong relationship among plasma inflammatory factors, sex steroid hormones, and the intestinal flora of patients.

Dietary inulin may improve obese PCOS women disease through the gut flora-inflammation-steroid hormone pathway.

ChiCTR-IOR-17012281.

The human gut microbiota plays a crucial role in maintaining metabolic health, with substantial evidence linking its composition to insulin resistance. This study aims to analyze the global scholarly contributions on the relationship between intestinal microbiota and insulin resistance from 2000 to 2024.

A bibliometric analysis was conducted using data from Scopus and Web of Science Core Collection. The search strategy included terms related to "Gastrointestinal Microbiome" and "Insulin Resistance" in the title or abstract.

The analysis of 1,884 relevant studies from 510 sources was conducted, revealing a mean citation of 51.36 per manuscript and a remarkable annual growth rate of 22.08%. The findings highlight the significant role of gut microbiota in insulin resistance, corroborating prior studies that emphasize its influence on metabolic disorders. The literature review of the current study showed key mechanisms include the regulation of short-chain fatty acids (SCFAs) and gut hormones, which are critical for glucose metabolism and inflammation regulation. The analysis also identifies "Food and Function" as the most productive journal and Nieuwdorp M. as a leading author, underscoring the collaborative nature of this research area.

The consistent increase in publications in the field of gut microbiota and insulin resistance indicates growing recognition of the gut microbiota's therapeutic potential in treating insulin resistance and related metabolic disorders. Future research should focus on standardizing methodologies and conducting large-scale clinical trials to fully realize these therapeutic possibilities.

Polycystic ovary syndrome (PCOS) is a common disease associated with high androgen and infertility. The gut microbiota plays an important role in metabolic diseases including obesity, hyperglycemia, and fatty liver. Although the gut microbiota has been associated with PCOS, little is known about the gut microbial structure and function in individuals with PCOS from Northeast China. In this study, 17 PCOS individuals and 17 age-matched healthy individuals were recruited for community structure and function analysis of the gut microbiota. The results showed that PCOS individuals have reduced diversity and richness of the gut microbiota compared with healthy individuals. Beta diversity analysis showed that the community structure of the gut microbiota of individuals with PCOS was significantly separated from healthy individuals. At the phylum level, PCOS individuals have reduced Firmicutes and Bacteroidota and increased Actinobacteriota and Proteobacteria compared with healthy individuals. At the family and genus levels, the composition of the gut microbiota between PCOS patients and healthy individuals was also significantly different. In addition, PICRUSt2 showed that individuals with PCOS have different microbial functions in the gut compared with healthy individuals. We finally confirmed that Bifidobacterium was enriched in the fecal samples of PCOS patients, while other 11 genera including Bacteroides, UCG_002, Eubacterium__coprostanoligenes_group_unclassified, Dialister, Firmicutes_unclassified, Ruminococcus, Alistipes, Christensenellaceae_R_7_group, Clostridia_UCG_014_unclassified, Roseburia, and Lachnospiraceae_unclassified were depleted compared with healthy individuals. These results indicate that individuals with PCOS have altered community structure and functions of the gut microbiota, which suggests that targeting the gut microbiota might be a potential strategy for PCOS intervention.

Gut microbiota plays a critical role in the development of PCOS. There is a complex and close interaction between PCOS and gut microbiota. The relationship between the pathogenesis and pathophysiological processes of PCOS and the structure and function of the gut microbiota needs further investigation.

Polycystic Ovary Syndrome (PCOS), which is common among women of reproductive age, is characterized by low-grade chronic inflammation and is associated with several health problems and dysbiosis. Kefir has been shown to have many beneficial health effects; however, its effect on PCOS is unknown. This study aimed to examine the effect of kefir on the intestinal microbiota and health outcomes in PCOS. In this intervention study, 17 women with PCOS consumed 250 mL/day of kefir (containing Lactobacillus kefiranofaciens subsp. kefiranofaciens, Lactobacillus kefiranofaciens subsp. kefirgranum, Lactobacillus kefiri, Lactobacillus acidophilus, Lactobacillus parakefiri, Lactobacillus bulgaricus, Lactobacillus reuteri, Lactobacillus casei, Lactobacillus fermentum, Lactobacillus helveticus, Lactococcus lactis, Leuconostoc mesentereoides, Bifidobacterium bifidum, Streptococcus thermophilus, Kluyveromyces marxianus, Kluyveromyces lactis, Acetobacter pasteurianus, and Saccharomyces cerevisiae) for 8 weeks. Food consumption and physical activity records, anthropometrical measurements, quality of life, and fecal and blood samples were taken at the study's beginning and end. Quality of life in mental health (58.8 ± 15.08; 64.0 ± 15.23, respectively) and physical function (95.00 and 100.00, respectively) categories showed a significant increase after kefir intervention (p < .05). Additionally, Interleukin-6 (IL-6), one of the inflammatory cytokines, significantly decreased (174.00 and 109.10 ng/L, respectively) (p < .05). The intestinal barrier permeability was evaluated with zonulin, and no significant change was observed. Gut microbiota analysis showed that while the relative abundance of the class Bacilli and genus Lactococcus significantly increased, the genus Holdemania decreased with kefir consumption (p < .05). In conclusion, kefir appears to be beneficial for improving the microbiota and some health outcomes, like reducing inflammation and improving quality of life in PCOS. Therefore, kefir may be useful in the treatment of PCOS.

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)-induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ + adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle-stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle-stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone-binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites-brain-ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin-1), lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. KEY POINTS: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS). Adropin regulated the ovarian steroidogenesis and sex hormone-binding globulin in PCOS. Adropin improved lipid profile and decreased insulin resistance in PCOS. Adropin modulated the components of the gut-brain-ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS. Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS.

It has been suggested that dysbiosis of the gut microbiota is associated with the pathogenesis of Polycystic Ovary Syndrome (PCOS), and that improper diet can aggravate these changes. This study thus aimed to investigate the effects of a high-fat/high-fructose (HF/HFr) diet on the gut microbial community and their metabolites in prepubertal female mice with letrozole (LET)-induced PCOS. We also tested the correlations between the relative abundance of microbial taxa and selected PCOS parameters.

Thirty-two C57BL/6 mice were randomly divided into four groups (n = 8) and implanted with LET or a placebo, with simultaneous administration of a HF/HFr diet or standard diet (StD) for 5 wk. The blood and intestinal contents were collected after the sacrifice.

Placebo + HF/HFr and LET + HF/HFr had significantly higher microbial alpha diversity than either group fed StD. The LET-implanted mice fed StD had a significantly higher abundance of Prevotellaceae_UCG-001 than the placebo mice fed StD. Both groups fed the HF/HFr diet had significantly lower fecal levels of short-chain fatty acids than the placebo mice fed StD, while the LET + HF/HFr animals had significantly higher concentrations of lipopolysaccharides in blood serum than either the placebo or LET mice fed StD. Opposite correlations were observed between Turicibacter and Lactobacillus and the lipid profile, CONCLUSION: HF/HFr diet had a much stronger effect on the composition of the intestinal microbiota of prepubertal mice than LET itself.

Obesity is one of the major risk factors for diabetes. Excessive accumulation of fat leads to inflammation of adipose tissue, which can increase the risk of developing diabetes. Obesity-related chronic inflammation can result in anomalies in glucose-lipid metabolism and insulin resistance, and it is a major cause of β-cell dysfunction in diabetes mellitus. Thus, a long-term tissue inflammatory response is crucial for metabolic diseases, particularly type 2 diabetes. Chronic inflammation associated with obesity increases oxidative stress, secretes inflammatory factors, modifies endocrine variables, and interferes with insulin signalling pathways, all of which contribute to insulin resistance and glucose tolerance. Insulin resistance and diabetes are ultimately caused by chronic inflammation in the stomach, pancreas, liver, muscle, and fat tissues. In this article, we systematically summarize the latest research progress on the mechanisms of adipose tissue inflammation and insulin resistance, as well as the mechanisms of cross-talk between adipose tissue inflammation and insulin resistance, with a view to providing some meaningful therapeutic strategies for the treatment of insulin resistance by controlling adipose tissue inflammation.

Alzheimer disease, the leading cause of dementia, and polycystic ovary syndrome, one of the most prevalent female endocrine disorders, appear to be unrelated conditions. However, studies show that both disease entities have common risk factors, and the amount of certain protein marker of neurodegeneration is increased in PCOS. Reports on the pathomechanism of both diseases point to the possibility of common denominators linking them. Dysregulation of the kynurenine pathway, insulin resistance, and impairment of the hypothalamic-pituitary-gonadal axis, which are correlated with amyloid-beta aggregation are these common areas. This article discusses the relationship between Alzheimer disease and polycystic ovary syndrome, with a particular focus on the role of disorders of tryptophan metabolism in both conditions. Based on a review of the available literature, we concluded that systemic changes occurring in PCOS influence the increased risk of neurodegeneration.

This study investigated changes in plasma microbial-derived extracellular vesicles (EVs) in patients with polycystic ovary syndrome and insulin resistance (PCOS-IR) before and after metformin treatment, and aimed to identify bacterial taxa within EVs that were biologically and statistically significant for diagnosis and treatment.

The case-control study was conducted at Xiamen Chang Gung Hospital, Hua Qiao University. Plasma samples were collected from five PCOS-IR patients of childbearing age before and after 3 months of metformin treatment, and the samples were sequenced. The diversity and taxonomic composition of different microbial communities were analyzed through full-length 16 S glycosomal RNA gene sequencing.

After metformin treatment, fasting plasma glucose levels and IR degree of PCOS-IR patients were significantly improved. The 16 S analysis of plasma EVs from metformin-treated patients showed higher microbial diversity. There were significant differences in EVs derived from some environmental bacteria before and after metformin treatment. Notably, Streptococcus salivarius was more abundant in the metformin-treated group, suggesting it may be a potential probiotic.

The study demonstrated changes in the microbial composition of plasma EVs before and after metformin treatment. The findings may offer new insights into the pathogenesis of PCOS-IR and provide new avenues for research.

Diabetic nephropathy is a common complication of diabetes and a considerable contributor to end-stage renal disease. Evidence indicates that glucose dysregulation and lipid metabolism comprise a pivotal pathogenic mechanism in diabetic nephropathy. However, current treatment outcomes are limited, as they only provide symptomatic relief without preventing disease progression. The gut microbiota is a group of microorganisms that inhabit the human intestinal tract and play a crucial role in maintaining host energy balance, metabolism, and immune activity. Patients with diabetic nephropathy exhibit altered gut microbiota, suggesting its potential involvement in the onset and progression of the disease. However, how a perturbed microbiota induces and promotes diabetic nephropathy remains unelucidated. This article summarizes the evidence of the impact of gut microbiota on the progression of diabetic nephropathy, with a particular focus on the molecular mechanisms involved, aiming to provide new insights into the treatment of diabetic nephropathy.

Dietary fiber (DF) consumption was reported to improve insulin sensitivity, change the tryptophan metabolism, and alter the gut microbiota. Herein, this study aimed to investigate the effects of DF consumption on insulin sensitivity, tryptophan metabolism, and gut microbiota composition in sows during late pregnancy, and explore the relationship between tryptophan metabolites and insulin sensitivity regulated by DF supplementation.

Twelve sows were randomly assigned to two dietary treatment groups (six/group): the low-fiber (LF) group, which was fed a basal diet, and the high-fiber (HF) group, which was fed the basal diet supplemented with 22.60 g/kg inulin and 181.60 g/kg cellulose. During late pregnancy, meal test, glucose tolerance test, and insulin challenge test were used to investigate the insulin sensitivity of sows, using the percutaneous brachiocephalic vein catheterization technique. High DF consumption resulted in improved insulin sensitivity, especially during the second and third trimesters, and promoted serotonin production from tryptophan. Additionally, plasma serotonin concentration was positively correlated with the insulin sensitivity index during late pregnancy. Moreover, DF consumption elevated fecal short-chain fatty acid (SCFA) concentrations, altered fecal microbial diversity, and increased the abundances of Rikenellaceae_RC9_gut_group, Alloprevotella, Parabacteroides, Roseburia, and Sphaerochaeta, which were positively correlated to plasma serotonin concentration.

DF consumption improved insulin sensitivity during late pregnancy in sows, which improved microbial diversity in fecal samples and increased fecal SCFA concentrations, resulting in a positive correlation with plasma serotonin level.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions?

Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs.

Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs.

This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included.

A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method.

We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03).

Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population.

The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs.

This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare.

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Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.

Mice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS).

In this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).

These results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.