Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism

Torres, Pedro J.; Siakowska, Martyna; Banaszewska, Beata; Pawełczyk, Leszek; Dulęba, Antoni J.; Kelley, Scott T.; Thackray, Varykina G.

doi:10.1210/jc.2017-02153

Cited by 276 publications

(270 citation statements)

References 40 publications

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“…With regards to PCOS, several recent studies reported that changes in the gut microbiome are associated with PCOS (23–26). These studies detected lower alpha diversity and differences in the relative abundances of specific Bacteroidetes and Firmicutes in women with PCOS compared to control individuals (23–25). In particular, decreases in the relative abundance of Bacteroides and genera from the Ruminococcaceae and S24-7 families were observed in several studies.…”

Section: Introductionmentioning

confidence: 83%

“…In particular, decreases in the relative abundance of Bacteroides and genera from the Ruminococcaceae and S24-7 families were observed in several studies. In addition, changes in the gut microbiome correlated with hyperandrogenism (25), suggesting that testosterone may influence the composition of the gut microbiome in females. In addition to studies in humans, several studies reported a significant association between the gut microbiome and PCOS in rodent models (27, 28).…”

Section: Introductionmentioning

confidence: 99%

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Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Torres

Ho²,

Arroyo³

et al. 2018

Preprint

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48Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 49 10% of reproductive-aged women worldwide. Diagnosis requires two of the following: 50 hyperandrogenism, oligo/anovulation and polycystic ovaries. In addition to reproductive 51 dysfunction, many women with PCOS display metabolic abnormalities associated with 52hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women 53with PCOS and rodent models of the disorder. However, it is unknown whether the gut 54 microbiome plays a causal role in the development and pathology of PCOS. Given its potential 55role, we hypothesized that exposure to a healthy gut microbiome would protect against 56 development of PCOS. A co-housing study was performed using a letrozole-induced PCOS 57 mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Since 58 mice are coprophagic, co-housing results in repeated, non-invasive inoculation of gut microbes 59 in co-housed mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, 60letrozole-treated mice co-housed with placebo mice showed significant improvement in both 61reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we observed 62 that the gut microbial composition of letrozole-treated mice co-housed with placebo mice 63 differed from letrozole mice housed together. In addition, our analyses identified several 64 bacterial taxa including Coprobacillus, Dorea and Adlercreutzia associated with the improved 65PCOS phenotype in letrozole-treated mice co-housed with placebo mice. These results indicate 66 that disruption of the gut microbiome may play a causal role in PCOS and that manipulation of 67 the gut microbiome may be a potential treatment option for PCOS. 68 69Significance: 70 71PCOS is a common cause of female infertility and ~80% of women with PCOS have metabolic 72 dysregulation that predisposes them to type 2 diabetes and cardiovascular disease. Since 73 treatment options for the metabolic symptoms of PCOS are limited, there is a need to develop 74 novel therapeutic options. The gut microbiome has emerged as an important player in human 75health and has been shown to play a causal role in obesity. In this study, we found that exposure 76to a healthy gut microbiome through co-housing protected against the development of 77reproductive and metabolic dysregulation in a PCOS mouse model. These results suggest that 78 manipulation of the gut microbiome may be a potential treatment option for women with PCOS. 79 80Introduction: 81 82Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting approximately 83 10% of women worldwide (1). Diagnosis of PCOS, using the Rotterdam Consensus criteria 84 (2003), requires two of the following: hyperandrogenism, oligo-or amenorrhea and polycystic 85ovaries. PCOS is the leading cause of anovulatory infertility in women, and women with PCOS 86also have an increased likelihood of miscarriage and pregnancy complications. Though ...

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Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Torres

Ho²,

Arroyo³

et al. 2018

Preprint

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“…Prevalence of glucose intolerance, type 2 diabetes, obesity, dyslipidemia and metabolic syndrome are increased in PCOS. [3][4][5][6][7] Alterations of gut microbiota or dysbiosis may affect various host metabolic pathways through microbiota-derived metabolites and can play a role in the development of diabetes, obesity and cardiovascular disease. However, whether this increased cardiovascular risk at young age translates into premature or higher morbidity or mortality later in life is yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

“…2 Recent animal and human data in PCOS showed alterations in composition of gut microbiota in PCOS, partly associated with androgen excess. [3][4][5][6][7] Alterations of gut microbiota or dysbiosis may affect various host metabolic pathways through microbiota-derived metabolites and can play a role in the development of diabetes, obesity and cardiovascular disease. 8,9 Trimethylamine N-oxide (TMAO)…”

Section: Introductionmentioning

confidence: 99%

Circulating gut microbiota metabolite trimethylamine N‐oxide and oral contraceptive use in polycystic ovary syndrome

Eyüpoğlu

Guzelce

Açıkgöz

et al. 2019

Clinical Endocrinology

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Objectives: Polycystic ovary syndrome (PCOS) is associated with an increased cardiometabolic risk that might not necessarily translate into adverse cardiovascular outcome later in life. Recently, alterations in gut microbial composition have been reported in the syndrome. Microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and its precursors are closely linked with development of atherosclerotic cardiovascular disease, independently of traditional risk factors. We aimed to assess whether TMAO and its precursors are altered in PCOS and to determine potential impact of treatment on these metabolites. Design: Prospective study.Patients: Twenty-seven overweight/obese patients with PCOS and 25 age-and BMImatched healthy control women.Measurements: At baseline, fasting serum TMAO and its precursors were measured after a 3-day standardized diet. Patients received 3-month OC therapy along with general dietary advice after which all measurements were repeated. Results: Patients had higher total testosterone (T) and free androgen index (FAI)whereas whole-body fat mass, fasting plasma glucose, insulin and lipids were similar between the groups. PCOS group showed significantly higher serum levels of TMAO and its precursors; choline, betaine and carnitine. TMAO and choline showed correlations with T. After 3 months of OC use, TMAO and its precursors significantly decreased along with reductions in BMI, T and FAI. Conclusions:This study reports for the first time that TMAO and its precursors are elevated in PCOS which might contribute to increased cardiometabolic risk of the syndrome and that short-term OC use along with lifestyle intervention is associated with reduction of these microbiome-dependent metabolites. K E Y W O R D Scardiometabolic risk, microbiome, oral contraceptives, polycystic ovary syndrome, trimethylamine N-oxide | 811 EYUPOGLU Et aL.

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“…To date, a few observational studies on the gut microbiome of individuals with PCOS exist [20,22,28,42,43]. Bifidobacterium intake resulted in lower insulin concentration, insulin resistance and higher insulin sensitivity in patients after a 12-week intervention [44].…”

Section: Discussionmentioning

confidence: 99%

Bifidobacteriumis enriched in gut microbiome of Kashmiri women with polycystic ovary syndrome

Hassan

Draisma

et al. 2019

Preprint

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Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age understudied in non-European populations. In India, PCOS affects the life of up to 19.4 million women of age 14-25 years. Gut microbiome composition might contribute to PCOS susceptibility.We profiled the microbiome in DNA isolated from faecal samples by 16S rRNA sequencing in 19/20 women with/without PCOS from Kashmir, India. We assigned genera to sequenced species with an average 121k reads depth and included bacteria detected in at least 1/3 of the subjects or with average relative abundance ≥0.1%. We compared the relative abundances of 40/58 operational taxonomic units in family/genus level between cases and controls, and in relation to 33 hormonal and metabolic factors, by multivariate analyses adjusted for confounders, and corrected for multiple testing. Seven genera were significantly enriched in PCOS cases: Sarcina, Alkalibacterium and Megasphaera, and previously reported for PCOS Bifidobacterium, Collinsella, Paraprevotella and Lactobacillus. We identified significantly increased relative abundance of Bifidobacteriaceae (median 6.07% vs. 2.77%) and Aerococcaceae (0.03% vs. 0.004%), whereas we detected lower relative abundance Peptococcaceae (0.16% vs. 0.25%) in PCOS cases. For the first time, we identified a significant direct association between butyrate producing Eubacterium and follicle-stimulating hormone levels. We observed increased relative abundance of Collinsella and Paraprevotella with higher fasting blood glucose levels, and Paraprevotella and Alkalibacterium with larger hip and waist circumference, and weight. We show a relationship between gut microbiome composition and PCOS linking it to specific reproductive health metabolic and hormonal predictors in Indian women.

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Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism

Abstract: These results suggest that hyperandrogenism may play a critical role in altering the gut microbiome in women with PCOS.

Cited by 276 publications

References 40 publications

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Exposure to a Healthy Gut Microbiome Protects Against Reproductive and Metabolic Dysregulation in a PCOS Mouse Model

Circulating gut microbiota metabolite trimethylamine N‐oxide and oral contraceptive use in polycystic ovary syndrome

Bifidobacteriumis enriched in gut microbiome of Kashmiri women with polycystic ovary syndrome

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