Beyond the reproductive tract: gut microbiome and its influence on gynecological health.

PURPOSE OF REVIEW: The analysis of microbiome in association with female health is today a "hot topic" with the main focus on microbes in the female reproductive tract. Nevertheless, recent studies are providing novel information of the possible influence of the gut microbiome on gynecological health outcomes, especially as we start to understand that the gut microbiome is an extended endocrine organ influencing female hormonal levels. This review summarizes the current knowledge of the gut microbes in association with gynecological health. RECENT FINDINGS: The gut microbiome has been associated with endometriosis, polycystic ovary syndrome, gynecological cancers, and infertility, although there is a lack of consistency and consensus among studies due to different study designs and protocols used, and the studies in general are underpowered. SUMMARY: The interconnection between the gut microbiome and reproductive health is complex and further research is warranted. The current knowledge in the field emphasizes the link between the microbiome and gynecological health outcomes, with high potential for novel diagnostic and treatment tools via modulation of the microenvironment.

Gut Microbiota in Patients with Polycystic Ovary Syndrome: a Systematic Review.

Polycystic ovary Syndrome (PCOS) is one of the most popular diseases that cause menstrual dysfunction and infertility in women. Recently, the relationships between the gastrointestinal microbiome and metabolic disorders such as obesity, type 2 diabetes and PCOS have been discovered. However, the association between the gut microbiome and PCOS symptoms has not been well established. We systematically reviewed existing studies comparing gut microbial composition in PCOS and healthy volunteers to explore evidence for this association. A systematic search was carried out in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 26, 2020, for all original cross-sectional, cohort, or case-control studies comparing the fecal microbiomes of patients with PCOS with microbiomes of healthy volunteers (controls). The primary outcomes were differences in specific gut microbes between patients with PCOS and controls. The search identified 256 citations; 10 studies were included. The total population study of these articles consists of 611 participants (including PCOS group and healthy controls group). Among the included 10 studies, nine studies compared α-diversity, and six studies demonstrated that α-diversity has a significant reduction in PCOS patients. Seven of them reported that there was a significant difference of ß-diversity composition between healthy controls groups and PCOS patients. The most common bacterial alterations in PCOS patients included Bacteroidaceae, Coprococcus, Bacteroides, Prevotella, Lactobacillus, Parabacteroides, Escherichia/Shigella, and Faecalibacterium prausnitzii. No consensus has emerged from existing human studies of PCOS and gut microbiome concerning which bacterial taxa are most relevant to it. In this systematic review, we identified specific bacteria associated with microbiomes of patients with PCOS vs controls. Higher level of evidence is needed to determine whether these microbes are a product or cause of PCOS.

Effects of Sleeve Gastrectomy on Fecal Gut Microbiota and Short-Chain Fatty Acid Content in a Rat Model of Polycystic Ovary Syndrome.

Purpose: Sleeve gastrectomy (SG) is a surgical intervention for polycystic ovary syndrome (PCOS), especially for patients with obesity. Here, we explored the effects of SG on the gut microbiota of rats with PCOS and investigated the association between the intestinal flora and efficacy of SG in PCOS. Methods: Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat diet to induce PCOS in rats. SG was performed in rats with PCOS, and the effects of SG on the fecal and gut microbiota and the short-chain fatty acid (SCFA) content were observed. Furthermore, the association among gut microbiota, SCFA content and hyperandrogenism or other hallmarks of PCOS was evaluated. Results: The abundance of Firmicutes reduced and that of Bacteroidetes increased in response to SG in the DHEA-induced PCOS rat model. At the genus level, the abundances of Bacteroides and Blautia increased and those of Ruminococcus, Clostridium, and Alistipes reduced distinctly in the PCOS-SG groups. Moreover, the levels of fecal SCFAs, especially butyric acid, reduced after SG. SG significantly ameliorated PCOS-related symptoms such as hyperandrogenism, disrupted ovary function, and impaired glucose tolerance. Bacteroides and Blautia exhibited a negative correlation and Ruminococcus, Clostridium, and Alistipes exhibited a positive correlation with the levels of fecal SCFAs, luteinizing hormone, testosterone, and inflammatory factors. Conclusions: The amelioration of PCOS-related reproductive and metabolic disorders following SG was associated with the regulation of microbial taxa and SCFA content. Our findings provide a novel perspective on the microbial mechanisms in PCOS after SG.

Effects of Soy Isoflavones, Resistant Starch and Antibiotics on Polycystic Ovary Syndrome (PCOS)-Like Features in Letrozole-Treated Rats.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Recently, various dietary interventions have been used extensively as a novel therapy against PCOS. In the present study, we show that soy isoflavone metabolites and resistant starch, together with gut microbiota modulations, were successful in decreasing the severity of PCOS-like reproductive features while increasing the expression of gut barrier markers and butyric acid in the gut. In the letrozole-induced PCOS model rats, the intake of both 0.05% soy isoflavones and 11% resistant starch, even with letrozole treatment, reduced the severity of menstrual irregularity and polycystic ovaries with a high concentration of soy isoflavones and equol in plasma. Antibiotic cocktail treatment suppressed soy isoflavone metabolism in the gut and showed no considerable effects on reducing the PCOS-like symptoms. The mRNA expression level of occludin significantly increased with soy isoflavone and resistant starch combined treatment. Bacterial genera such as Blautia, Dorea and Clostridium were positively correlated with menstrual irregularity under resistant starch intake. Moreover, the concentration of butyric acid was elevated by resistant starch intake. In conclusion, we propose that both dietary interventions and gut microbiota modulations could be effectively used in reducing the severity of PCOS reproductive features.

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

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 α-diversity of the gut microbiome of the PNA group was higher at 8 weeks and lower at 12 and 16 weeks of age, and the ß-diversity 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.

Polycystic ovary syndrome and cardiovascular risk. Could trimethylamine N-oxide (TMAO) be a major player? A potential upgrade forward in the DOGMA theory.

Several studies reported an increase in cardiovascular risk (CVR) in women with polycystic ovary syndrome (PCOS), considered primarily as the result of the combination of all the clinical features that characterize the syndrome, including hyperandrogenism, insulin resistance, diabetes, obesity chronic low-grade inflammation. Interestingly, in 2012 it has been proposed the so-called DOGMA theory, suggesting the pivotal role played by microbiota alteration in the development of PCOS. Subsequently, several authors evidenced the existence in PCOS women of a marked dysbiosis, which is related to the development of metabolic diseases and cardiovascular complications, mainly due to the production of bacteria-derived metabolites that interfere with various pathways. Among these, trimethylamine-N-oxide (TMAO) is emerging as one of the most important and studied microbiota-derived metabolites related to the increase in CVR, due to its pro-atherosclerotic effect. The purpose of the present review is to summarize the evidence in order to support the hypothesis that, in women with PCOS, dysbiosis might be further involved in enhancement of the CVR via contributing to the increase of circulating TMAO. Although no observational studies on a large number of patients directly investigated the serum levels of TMAO in PCOS women, this manuscript aimed to drive future studies in this field, concurring in providing a novel approach for both comprehension and treatment of the CVR in PCOS.

Gut microbiota as the critical correlation of polycystic ovary syndrome and type 2 diabetes mellitus.

Gut microbiota forms a symbiotic relationship with the host and maintains the ecological balance of the internal and external environment of the human body. However, dysbiosis of the gut microbiota and immune deficiency, as well as environmental changes, can destroy the host-microbial balance, leading to the occurrence of a variety of diseases, such as polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), and obesity. Meanwhile, diseases can also affect gut microbiota, forming a vicious cycle. The role of the intestinal microbiota in different diseases have been proven by several studies; however, as a common target of PCOS and T2DM, there are few reports on the treatment of different diseases through the regulation of intestinal microbiota as the critical correlation. This review analyzed the common mechanisms of intestinal microbiota in PCOS and T2DM, including the dysbiosis of gut microbiota, endotoxemia, short-chain fatty acids, biotransformation of bile acids, and synthesis of amino acid in regulating insulin resistance, obesity, chronic inflammation, and mitochondrial dysfunction. The possible therapeutic effects of probiotics and/or prebiotics, fecal microbiota transplantation, bariatric surgery, dietary intervention, drug treatment, and other treatments targeted at regulating intestinal microbiota were also elucidated.

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

CONTEXT: The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear. OBJECTIVE: 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. SETTING AND DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical Manifestations of Polycystic Ovary Syndrome and Associations With the Vaginal Microbiome: A Cross-Sectional Based Exploratory Study.

Background: Previous studies suggest that the vaginal microbiome is associated with polycystic ovary syndrome (PCOS). However, the clinical manifestations of PCOS are heterogeneous. Whether the vaginal microbiome is related with different clinical symptoms was unknown. Materials and Methods: In this cross-sectional study, 89 female patients with PCOS admitted to Zhongda Hospital (Nanjing, China) were included. Basic demographic information, health-related behaviors, clinical manifestations and sex hormone levels were comprehensively recorded for all patients. Vaginal swabs were acquired for microbiota sequencing of the V3-V4 region of the 16S rRNA gene. Results: The prevalence of bacterial vaginitis and vulvovaginal candidiasis was 15.7% and 13.5%, respectively, within the PCOS patients, which were the most important factors affecting the vaginal microbiome (permutational multivariate analysis of variance test, R2 = 0.108, P = 0.001). The vaginal microbiome was associated with specific clinical manifestations of PCOS, including acanthosis nigricans, intermenstrual bleeding, pregnancy history, testosterone level and anti-müllerian hormone level, with P values < 0.05. The abundance of Lactobacillus crispatus was higher (P = 0.010) while that of Lactobacillus iners was lower (P = 0.036) among PCOS patients with elevated testosterone levels. Other potential bacterial biomarkers were not statistically significant after adjusting for confounding factors. No evidence of associations of other common manifestations of PCOS, such as obesity and acne, with the vaginal microbiome was obtained. Conclusion: Vaginal bacterial species among PCOS patients with variable clinical manifestations, especially differences in testosterone levels, are distinct. Further studies are essential to investigate the microbiota and molecular mechanisms underpinning this disease.

Microbiome and PCOS: State-of-Art and Future Aspects.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract microbiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid.

Guild-based analysis for understanding gut microbiome in human health and diseases.

To demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem's higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same "guild" if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of "guild" to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.

Characterization on gut microbiome of PCOS rats and its further design by shifts in high-fat diet and dihydrotestosterone induction in PCOS rats.

Polycystic ovary syndrome (PCOS) is associated with gut microbiota disturbance. Emerging evidence has shown that gut microbiota plays a major role in the development of PCOS. To better understand how the gut microbiota contributes to the development of PCOS, we investigated the influences of high-fat diet and hyperandrogenism, independently or synergistically, have on the gut microbiota in rats. Furthermore, we explored the associations between gut microbiota and hyperandrogenism or other hallmarks of PCOS. Twenty female SD rats were randomized at aged 3 weeks into 4 groups (n = 5, each); HA: PCOS rats fed with ordinary diet; HF: rats with high-fat diet (HFD); HA-HF: PCOS rats fed with HFD; and C: control rats with ordinary diet. PCOS rat model was induced by 5α-dihydrotestosterone (DHT) injection for 6 weeks. The fasting blood glucose (FBG), plasma insulin, testosterone, free testosterone, TNF-α, MDA, SOD, LPS, TLR4, TG, TC, HDL-C, and LDL-C levels were measured. The molecular ecology of the fecal gut microbiota was analyzed by 16S rDNA high-throughput sequencing. The results showed that rats in the HA and HA-HF group displayed abnormal estrous cycles with increasing androgen level and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Compare with the C group, relative abundance of the Bacteroidetes phylum decreased significantly in the other groups (P < 0.05). The Chao1 was the highest in the group C and significantly higher than the HA-HF group (P < 0.05). T, FT, insulin, MDA, LPS, and TNF-α levels had the negative correlation with the richness of community (Chao1 index) in the gut. The rats in the HF and HA-HF groups tended to have lower Shannon and Simpson indices than the C group (P < 0.01, respectively). However, there were no significant differences between C group and the HA group in the Shannon and Simpson values. Beta diversity analysis was then performed based on a weighted UniFrac analysis. The PCoA plots showed a clear separation of the C group from the other groups. ANOSIM analysis of variance confirmed that there were statistically significant separations between the C group and the HA, HA-HF, and HF groups (P < 0.01, respectively). These results showed that DHT with HFD could lower diversity of the gut microbial community. Both HFD and DHT could shift the overall gut microbial composition and change the composition of the microbial community in gut. Furthermore, our analyses demonstrated that the levels of TG, MDA, TNF-α, LPS, TLR4, T, FT, FINS, and HDL-C were correlated with the changes of in the gut microbiome. HFD and DHT were associated with the development and pathology of PCOS by shaping gut microbial communities.

Characterization of gut microbiota in polycystic ovary syndrome: Findings from a lean population.

BACKGROUND: Limited available animal and human data suggest an association between dysbiosis of gut microbiota and PCOS. We aimed to determine whether gut microbiota in lean women with PCOS shows any alterations compared to healthy women. MATERIALS AND METHODS: Twenty-four lean patients with PCOS phenotype A according to the Rotterdam 2003 diagnostic criteria and 22 BMI-matched healthy women were included in this study. Anthropometric, hormonal and biochemical measurements were carried out in all participants. 16S rRNA gene V3-V4 region amplicon sequencing was performed on stool samples. Preprocessing of the raw data was performed using QIIME, and both QIIME and R packages were used for microbiome analysis. RESULTS: Bacterial richness and diversity did not show a significant difference between patients and controls. Beta diversity was similar between the groups. However, Erysipelotrichaceae, Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, Planococcaceae, Gemmules and Bacillales were significantly abundant in PCOS group according to LEfSe analysis. Clostridium cluster XVII showed increased abundance in patient group, while Clostridium sensustricto and Roseburia were decreased compared to controls. Random forest prediction analysis revealed Clostridium cluster XIVb as the most discriminative feature of patient group and Roseburia for healthy controls. Testosterone and androstenedione were negatively correlated with alpha and phylogenetic diversity. CONCLUSIONS: Our results suggest that gut microbiome of lean PCOS patients with full phenotype shows compositional alterations with similar bacterial richness and diversity compared to controls and that hyperandrogenism is associated with dysbiosis.

Alterations in the intestinal microbiome associated with PCOS affect the clinical phenotype.

Polycystic ovarian syndrome (PCOS), characterized by chronic anovulation and hyperandrogenaemia, is a complex endocrine and metabolic disorder commonly seen in women of reproductive age. Multiple factors, including the intestinal microbiome, affect the pathogenesis and development of PCOS. However, the specific mechanisms by which gut microbes play a role in PCOS remain elusive. This review summarizes recent research about the transformational changes in gut microbes revealed in PCOS patients and the possible mechanisms and pathways by which the intestinal microbiome exerts influence on PCOS progression and phenotypes. In addition to the intestinal microbiome, evidence from animal studies suggests changes in the vaginal microbiome under PCOS conditions. The alteration of microbiome could affect oestrus cycle and PCOS phenotypes. Microbiome is closely associated with medicine and therapeutic approaches. Microbiome influences drug and therapy response and itself is a new source of therapy. Accurate modulation of the intestinal and vaginal microbiome is a potential therapy for PCOS patients. Future studies are required to elucidate the specific role of each particular genera of microbiota and the mechanism by which microbiome impacts the pathogenesis, progression and phenotypes of PCOS.

The Gut Microbiome in Polycystic Ovary Syndrome and Its Association with Metabolic Traits.

CONTEXT: Despite the gut microbiome being widely studied in metabolic diseases, its role in polycystic ovary syndrome (PCOS) has been scarcely investigated. OBJECTIVE: Compare the gut microbiome in late fertile age women with and without PCOS and investigate whether changes in the gut microbiome correlate with PCOS-related metabolic parameters. DESIGN: Prospective, case-control study using the Northern Finland Birth Cohort 1966. SETTING: General community. PARTICIPANTS: A total of 102 PCOS women and 201 age- and body mass index (BMI)-matched non-PCOS control women. Clinical and biochemical characteristics of the participants were assessed at ages 31 and 46 and analyzed in the context of gut microbiome data at the age of 46. INTERVENTION: (s): None. MAIN OUTCOME MEASURE(S): Bacterial diversity, relative abundance, and correlations with PCOS-related metabolic measures. RESULTS: Bacterial diversity indices did not differ significantly between PCOS and controls (Shannon diversity P = .979, unweighted UniFrac P = .175). Four genera whose balance helps to differentiate between PCOS and non-PCOS were identified. In the whole cohort, the abundance of 2 genera from Clostridiales, Ruminococcaceae UCG-002, and Clostridiales Family XIII AD3011 group, were correlated with several PCOS-related markers. Prediabetic PCOS women had significantly lower alpha diversity (Shannon diversity P = .018) and markedly increased abundance of genus Dorea (false discovery rate = 0.03) compared with women with normal glucose tolerance. CONCLUSION: PCOS and non-PCOS women at late fertile age with similar BMI do not significantly differ in their gut microbial profiles. However, there are significant microbial changes in PCOS individuals depending on their metabolic health.

Síndrome dos ovários policísticos e sua relação com a microbiota intestinal / Polycystic ovary syndrome and its relationship with the intestinal microbiota

Objetivo: Revisar a implicação e a relação existente entre a microbiota intestinal e a síndrome do ovário policístico (SOP). Métodos: Trata-se de uma revisão sistemática de artigos das bases de dados PubMed, Cochrane e Science Direct dos últimos cinco anos, nos idiomas inglês, português e espanhol. Resultados: A disbiose da microbiota intestinal ativa o sistema imunológico do hospedeiro. Tal ativação interfere na função do receptor de insulina, causando hiperinsulinemia, o que aumenta a produção de androgênio ovariano e dificulta o desenvolvimento de um folículo saudável. Além disso, pacientes com SOP apresentam o perfil taxonômico alterado, o qual se associou inversamente com excesso de andrógenos e inflamação da SOP. Foi evidenciado que o uso de probióticos pode regular a resposta inflamatória, diminuir os níveis totais de testosterona e contribuir para que a SOP não prejudique uma possível gravidez. Conclusão: Essa revisão sugere que há íntima associação entre a disbiose microbiana e as alterações patológicas que ocorrem na SOP. Assim, a suplementação de probióticos em tais pacientes pode ter grandes benefícios, como melhora dos sintomas e redução das repercussões da doença.(AU)

Objective: To review the implication and the relationship between the intestinal microbiota and polycystic ovary syndrome. Methods: This is a systematic review of articles from the PubMed, Cochrane and Science Direct databases, from the last five years, in English, Portuguese and Spanish. Results: Dysbiosis of the intestinal microbiota activates the host's immune system. Such activation interferes with the function of the insulin receptor, causing hyperinsulinemia, which increases the production of ovarian androgens and hinders the development of a healthy follicle. In addition, patients with PCOS have an altered taxonomic profile, which is inversely associated with excess androgens and PCOS inflammation. It was evidenced that the use of probiotics can regulate the inflammatory response, decrease the total testosterone levels and contribute so that PCOS does not harm a possible pregnancy. Conclusion: This review suggests that there is a close association between microbial dysbiosis and pathological changes that occur in PCOS. Thus, supplementation of probiotics in such patients can have great benefits, such as improving symptoms and reducing the repercussions of the disease.(AU)

Correlation Between Fecal Metabolomics and Gut Microbiota in Obesity and Polycystic Ovary Syndrome.

Objective: This study aimed to explore the relationship between the fecal metabolites and gut microbiota in obese patients with PCOS and provide a new strategy to elucidate the pathological mechanism of obesity and PCOS. Methods: The fecal samples of obese patients with PCOS (n = 18) and obese women without PCOS (n = 15) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The peripheral venous blood of all subjects was collected to detect serum sex hormones. The association among fecal metabolites, gut microbiota, and serum sex hormones was analyzed with the R language. Results: A total of 122 named differential fecal metabolites and 18 enrichment KEGG pathways were obtained between the groups. Seven fecal metabolites can be used as characteristic metabolites, including DHEA sulfate. The richness and diversity of gut microbiota in the obese PCOS group were lower than those in the control group. Lachnoclostridium, Fusobacterium, Coprococcus_2, and Tyzzerela 4 were the characteristic genera of the obese patients with PCOS. Serum T level significantly and positively correlated with the abundance of fecal DHEA sulfate (p < 0.05), and serum DHEAS level significantly and negatively correlated with the abundance of fecal teasterone (p < 0.05). Conclusion: Specific fecal metabolites may be used as characteristic metabolites for obese patients with PCOS. The closely relationship among gut microbiota, fecal metabolites, and serum sex hormones may play a role in the related changes caused by hyperandrogenemia.

Determination of the Role of Fusobacterium Nucleatum in the Pathogenesis in and Out the Mouth.

INTRODUCTION: One of the most important types of microorganisms in the oral cavity in both healthy and non-healthy individuals is Fusobacterium nucleatum. Although present as a normal resident in the oral cavity, this Gram-negative pathogen is dominant in periodontal disease and it is involved in many invasive infections in the population, acute and chronic inflammatory conditions, as well as many adverse events with a fatal outcome. AIM: To determine the role of F. nucleatum in the development of polymicrobial biofilms thus pathogenic changes in and out of the oral media. MATERIAL AND METHOD: A systematic review of the literature concerning the determination and role of F. nucleatum through available clinical trials, literature reviews, original research and articles published electronically at Pub Med and Google Scholar. CONCLUSION: The presence of Fusobacterium nucleatum is commonly associated with the health status of individuals. These anaerobic bacteria plays a key role in oral pathological conditions and has been detected in many systemic disorders causing complex pathogenethic changes probably due to binding ability to various cells thus several virulence mechanisms. Most common diseases and conditions in the oral cavity associated with F.nucleatum are gingivitis (G), chronic periodontitis (CH), aggressive periodontitis (AgP), endo-periodental infections (E-P), chronic apical periodontitis (PCHA). The bacterium has been identified and detected in many systemic disorders such as coronary heart disease (CVD) pathological pregnancy (P); polycystic ovary syndrome (PCOS), high-risk pregnancy (HRP), colorectal cancer (CRC); pre-eclampsia (PE); rheumatoid arthritis (RA); osteoarthritis (OA).

Impact of Short-Term Isoflavone Intervention in Polycystic Ovary Syndrome (PCOS) Patients on Microbiota Composition and Metagenomics.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide and is associated with disorders of glucose metabolism. Hormone and metabolic signaling may be influenced by phytoestrogens, such as isoflavones. Their endocrine effects may modify symptom penetrance in PCOS. Equol is one of the most active isoflavone metabolites, produced by intestinal bacteria, and acts as a selective estrogen receptor modulator. METHOD: In this interventional study of clinical and biochemical characterization, urine isoflavone levels were measured in PCOS and control women before and three days after a defined isoflavone intervention via soy milk. In this interventional study, bacterial equol production was evaluated using the log(equol: daidzein ratio) and microbiome, metabolic, and predicted metagenome analyses were performed. RESULTS: After isoflavone intervention, predicted stool metagenomic pathways, microbial alpha diversity, and glucose homeostasis in PCOS improved resembling the profile of the control group at baseline. In the whole cohort, larger equol production was associated with lower androgen as well as fertility markers. CONCLUSION: The dynamics in our metabolic, microbiome, and predicted metagenomic profiles underline the importance of external phytohormones on PCOS characteristics and a potential therapeutic approach or prebiotic in the future.