High-Fiber Diet or Combined With Acarbose Alleviates Heterogeneous Phenotypes of Polycystic Ovary Syndrome by Regulating Gut Microbiota

Abstract

ObjectiveGut microbial dysbiosis is associated with high heterogeneity of polycystic ovary syndrome (PCOS); however, studies about gut microbiota targeted clinical intervention in PCOS are limited. Our study aimed to evaluate the effects of high-fiber diet or combined with acarbose on the clinical phenotypes of PCOS, focusing on the possible influence of gut microbiota in this process.MethodsTwenty-five patients with PCOS were recruited and randomly divided into two groups, W group (n = 14) received the WTP diet (a high-fiber diet composed of whole grains, traditional Chinese medicinal foods, and prebiotics), and A group (n = 11) received the WTP diet combined with acarbose. The follow-up time was 12 weeks. The sex hormonal and glycolipid metabolic parameters, inflammatory factors, brain–gut peptides, and alteration of gut microbiota were evaluated.ResultsThe PCOS clinical phenotypes, inflammatory state, and brain–gut peptides secretion were all alleviated in both groups, while the hyperandrogenism, insulin resistance, and brain–gut peptides secretion were better improved in the A group. Alpha and beta diversities were altered more significantly in the A group. Amplicon sequence variants (ASVs) were clustered into 14 co-abundant groups (CAGs) as potential functional groups that may respond to the intervention. The CAGs predominantly comprised of Bifidobacterium and Lactobacillus were more enriched, while the CAGs predominantly comprised of Bacteroides vulgatus, Alistipes, Blautia, Lachnospira, and Roseburia were more inhibited in the A group than in W group. Moreover, the CAGs enriched in the A group had a stronger negative correlation with the luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, testosterone, homeostasis model assessment-insulin resistance (HOMA-IR), α-1-acid glycoprotein (α-AGP), and leptin, and positive correlation with adiponectin and spexin, while the CAGs inhibited showed an opposite trend.ConclusionsHigh-fiber diet could alleviate the chronic metabolic inflammation, reproductive function, and brain–gut peptides secretion of patients with PCOS, and high-fiber diet combined with acarbose could better improve the PCOS clinical phenotypes. The remodeling of gut microbiota by our intervention may play an important role in these improvements.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=4500, ChiCTR-TRC-14005075

Effects of dehydroepiandrosterone alone or in combination with a high-fat diet and antibiotic cocktail on the heterogeneous phenotypes of PCOS mouse models by regulating gut microbiota

“…A number of studies suggest that women with PCOS exhibit hyperandrogenism, multi-cystic ovaries, hyperinsulinemia, glucolipid metabolism disorders and obesity, which are related to the gut microbiota ( 14 , 26 , 27 ). However, women with PCOS often show high clinical heterogeneity, and our previous study found that the clinical heterogeneity of PCOS was related to the gut microbiota ( 18 ). Combined with reviews of PCOS rodent models over the past decades, we found that PCOS rodent models are often variable ( 9 , 10 ).…”

“…The above evidence proves that the gut microbiota participates in the two core pathogenic factors of PCOS via different pathways, suggesting that the gut microbiota may be related to the heterogeneity of PCOS. Our previous study found that the gut microbiota was closely related to the heterogeneous phenotypes of women with PCOS ( 18 ). However, the correlation between the gut microbiota and the heterogeneity of PCOS rodent models has not yet been studied.…”

Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment

“…Supplementation with probiotics, prebiotics, and synbiotics in women with PCOS can improve IR, protect the intestinal barrier, and regulate the immune system, lipid profile, and other metabolic disorders [193,194]. Recent studies have also found that a high-fibre diet consisting of whole grains, traditional Chinese medicinal foods, and prebiotics combined with the α-glucosidase inhibitor acarbose improved reproductive endocrine disorders, HI, and IR in women with PCOS compared with a highfibre diet alone [195]. Animal studies have shown that aloe gel extract can act as a potential metabolic regulator of PCOS by controlling glucose homoeostasis, improving insulin secretion, and enhancing insulin-mediated glucose uptake to reduce glucose tolerance [221,222].…”

“…Animal studies have shown that aloe gel extract can act as a potential metabolic regulator of PCOS by controlling glucose homoeostasis, improving insulin secretion, and enhancing insulin-mediated glucose uptake to reduce glucose tolerance [221,222]. Clinical trials have also shown that l-carnitine supplementation effectively improves PCOS-IR by improving fatty acid β-oxidation and carbohydrate metabolism [194,195,221]. A recent trial showed that metformin combined with pioglitazone and acetylcarnitine improved IR and ovulation in women with PCOS more than metformin plus pioglitazone [199].…”

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome

“…In general, in women suffering from PCOS, the increased abundance of Escherichia and Shigella leads to an altered production of short-chain fatty acids, while a lower abundance of Lactobacillus and Bifidobacterium species impairs the release of anti-inflammatory metabolites and reduces the immune response [ 146 ]. In this regard, dietary patterns that include large fiber consumption seem able to improve PCOS clinical manifestations just acting on gut microbiota; into specifics, a recent study has reported that a 12-week high-fiber diet, or in combination with Acarbose, favors Lactobacillus and Bifidobacterium abundance with a positive effect on LH/FSH ratio, testosterone, homeostasis model assessment-insulin resistance (HOMA-IR), α-1-acid glycoprotein (α-AGP) and leptin [ 147 ]. In murine PCPS models, dietary α-linolenic acid, which is an n3 PUFA, has been shown to modulate gut microbiota, increasing Lactobacillus and Bifidobacterium as well as Allobaculum, Butyrivibrio, Desulfovibrio, Faecalibacterium and Parabacteroides, with a consequent reduction of plasma and ovarian inflammatory cytokines, including IL-6,IL-1β, IL-10, IL-17A, TNFα and monocyte chemoattractant protein-1 [ 148 ].…”