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

Apr 22, 2024Probiotics and antimicrobial proteins

Gut Bacteria in Polycystic Ovary Syndrome and Related Conditions: Type 2 Diabetes, Fatty Liver, Heart Disease, and Possible Microbe-Based Treatments

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Abstract

Polycystic ovary syndrome (PCOS) is associated with lower microbial diversity and higher levels of opportunistic pathogens in the gut.

PCOS is linked to obesity, insulin resistance, chronic inflammation, and dyslipidemia.
A decrease in beneficial gut microbes, such as Faecalibacterium and Bifidobacterium, is observed in PCOS.
The presence of butyrate producers in the gut may support glucose metabolism and gut barrier function.
Increased levels of the gut enzyme β-glucuronidase in PCOS may lead to higher androgen levels due to reabsorption.
Dysbiosis in PCOS is associated with increased gut permeability, chronic inflammation, and potential progression to type 2 diabetes and cardiovascular diseases.
Microbial therapeutics, like probiotics and fecal microbiome transplantation, may provide a side-effect-free alternative to hormonal therapy for managing PCOS-related complications.

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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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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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