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Gut Microbes in Polycystic Ovary Syndrome and Associated Comorbidities; Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), Cardiovascular Disease (CVD), and the Potential of Microbial Therapeutics

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Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine anomalies among females of reproductive age, highlighted by hyperandrogenism. PCOS is multifactorial as it can be associated with obesity, insulin resistance, low-grade chronic inflammation, and dyslipidemia. PCOS also leads to dysbiosis by lowering microbial diversity and beneficial microbes, such as Faecalibacterium, Roseburia, Akkermenisa, and Bifidobacterium, and by causing a higher load of opportunistic pathogens, such as Escherichia/Shigella, Fusobacterium, Bilophila, and Sutterella. Wherein, butyrate producers and Akkermansia participate in the glucose uptake by inducing glucagon-like peptide-1 (GLP-1) and glucose metabolism, respectively. The abovementioned gut microbes also maintain the gut barrier function and glucose homeostasis by releasing metabolites such as short-chain fatty acids (SCFAs) and Amuc_1100 protein. In addition, PCOS-associated gut is found to be higher in gut-microbial enzyme β-glucuronidase, causing the de-glucuronidation of conjugated androgen, making it susceptible to reabsorption by entero-hepatic circulation, leading to a higher level of androgen in the circulatory system. Overall, in PCOS, such dysbiosis increases the gut permeability and LPS in the systemic circulation, trimethylamine N-oxide (TMAO) in the circulatory system, chronic inflammation in the adipose tissue and liver, and oxidative stress and lipid accumulation in the liver. Thus, in women with PCOS, dysbiosis can promote the progression and severity of type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). To alleviate such PCOS-associated complications, microbial therapeutics (probiotics and fecal microbiome transplantation) can be used without any side effects, unlike in the case of hormonal therapy. Therefore, this study sought to understand the mechanistic significance of gut microbes in PCOS and associated comorbidities, along with the role of microbial therapeutics that can ease the life of PCOS-affected women.

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Acknowledgements

We want to acknowledge that our wonderful friend, Aprajita Bhandari (Dore), is the main motivation behind this work; she has been suffering from PCOS since her teenage, and her health issues have made us realize the problems of women with PCOS. We also acknowledge the KNU NGS Core Facility (Kyungpook National University, Daegu, South Korea) for providing the facilities. Figures in this review were made using BioRender.

Funding

The present work was supported by the Biological Materials Specialized Graduate Program through the Korea Environmental Industry & Technology Institute (KEITI) funded by the Ministry of Environment (MOE) and the Korea Basic Science Institute (National Research Facilities and Equipment Center) grant, funded by the Ministry of Education (2021R1A6C101A416), Republic of Korea.

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  1. Vineet Singh and Kanika Mahra contributed equally to this work.

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  1. Department of Applied Biosciences, Kyungpook National University, Daegu, South Korea

    Vineet Singh, Kanika Mahra, DaRyung Jung & Jae-Ho Shin

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VS & KM conceptualized, analyzed, wrote, and drafted the manuscript; KM and VS made the illustrations; DJ participated in writing and management; JHS supervised, reviewed, and approved the manuscript.

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Correspondence to Jae-Ho Shin.

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Singh, V., Mahra, K., Jung, D. et al. Gut Microbes in Polycystic Ovary Syndrome and Associated Comorbidities; Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), Cardiovascular Disease (CVD), and the Potential of Microbial Therapeutics. Probiotics & Antimicro. Prot. (2024). https://doi.org/10.1007/s12602-024-10262-y

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  • DOI: https://doi.org/10.1007/s12602-024-10262-y

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