Diversity of the Gut Microbiota in Dihydrotestosterone-Induced PCOS Rats and the Pharmacologic Effects of Diane-35, Probiotics, and Berberine

Zhang, Feifei; Ma, Tong; Cui, Peng; Tamadon, Amin; He, Shan; Huo, Chuanbing; Gulinazi, Yierfulati; Xu, Xiaoqing; Hu, Wei; Li, Xin; Shao, Ruijin; Guo, Hongwei; Feng, Yi; Xu, Congjian

doi:10.3389/fmicb.2019.00175

Cited by 75 publications

(57 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Liu et al found a decrease in Ruminococcaceae and an increase in gram-negative bacteria, including Bacteroides and Desulfovibrio, in women with PCOS, which was consistent with our research (20). Regarding to the phylum level of the gut microbiota, we found that the abundances of Firmicutes, Bacteroidetes, and Proteobacteria were the most dominant in all groups, in consistence with previous studies (12,77). An increase in Firmicutes/Bacteroidetes ratio is closely related to obesity (12,78).…”

Section: Discussionsupporting

confidence: 92%

Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones—Microbiota—Inflammation Axis in Rats

et al. 2020

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) represents a common endocrine-metabolic disorder disease with chronic low-grade inflammation and alteration of intestinal flora. Serving as functional food, flaxseed oil (FO), which is rich in plant-derived α-linolenic acid of omega-3 polyunsaturated fatty acids, has been proven to benefit for chronic metabolic diseases. However, the exact role of dietary FO on PCOS remains largely unclear. In the present study, 6-week-old female Sprague-Dawley rats were randomly divided into four groups (eight rats/group), including (a) pair-fed (PF) control (CON) group (PF/CON), (b) FO-fed CON group (FO/CON), (c) PF with letrozole-induced PCOS model (MOD) group (PF/MOD), and (d) FO-fed MOD group (FO/MOD). All rats were fed a standard diet. After 3 weeks of modeling and subsequent 8 weeks of treatment, the rats in diverse groups were euthanized and associated indications were investigated. The results showed that dietary FO ameliorated the disorder of estrous cycle and ovarian morphology. In parallel, dietary FO improved the sex steroid hormone disturbance (luteinizing hormone/follicle-stimulating hormone, estrogen, testosterone, and progesterone), body weights, dyslipidemia, and insulin resistance. Moreover, FO treatment improved plasma and ovary inflammatory interleukin (IL)-1β, IL-6, IL-10, and IL-17A, tumor necrosis factor-α, and monocyte chemoattractant protein-1. Additionally, FO intervention significantly modulated the composition of gut microbiota and vaginal microbiota by increasing the abundances of Allobaculum, Lactobacillus, Butyrivibrio, Desulfovibrio, Bifidobacterium, Faecalibacterium, Parabacteroides as well as decreasing the abundances of Actinobacteria, Bacteroides, Proteobacteria, and Streptococcus, the ratio of Firmicutes/Bacteroidetes. A decrease in plasma lipopolysaccharide level and an increase in short-chain fatty acids, including acetic acid, propionic acid, butyric acid and pentanoic acid, were determined after dietary FO supplementation. Correlation analysis Wang et al. FO Ameliorates PCOS in Rats revealed close relationships among sex steroid hormones, inflammation, and gut/vaginal microbiota. Collectively, this study demonstrated that dietary FO ameliorated PCOS through the sex steroid hormones-microbiota-inflammation axis in rats, which may contribute to the understanding of pathogenesis and potentially serve as an inexpensive intervention in the control of PCOS.

show abstract

Section: Discussionsupporting

confidence: 92%

Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones—Microbiota—Inflammation Axis in Rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Combination of Diane-35 and metformin treatment could decrease the BMI and LU levels, improve the condition of hyperandrogenemia and insulin resistance in PCOS patients [5]. In the dihydrotestosterone-induced PCOS rats, Diane-35 was found to be effective to restore the reproductive functions [17]. Consistently, in the present study, we found that combination of Diane-35 and metformin treatment reduced body weight, decreased the levels of testosterone and luteinizing hormone and insulin resistance, and also restored the estrous cycle and ovulation in the PCOS rats, indicating that the combined treatment improved the PCOS complications.…”

Section: Discussionmentioning

confidence: 97%

Combined use of Diane-35 and metformin improves the ovulation in the PCOS rat model possibly via regulating glycolysis pathway

Zhang

Yao

et al. 2020

Reprod Biol Endocrinol

View full text Add to dashboard Cite

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disease with unknown pathogenesis. However, the treatment of Diane-35 combined with metformin can improve the endocrine and ovulation of PCOS. In this study, we investigated the effects of Diane-35 combined with metformin (DM) treatment on ovulation and glucose metabolism in a PCOS rat model. Methods: Sprague Dawley rats were divided into 3 groups, control group, model group (PCOS group) and Diane-35 combined with metformin (PCOS + DM group). The mRNA expression levels were determined by qRT-PCR. The hormone levels were determined by enzyme-linked immunosorbent assay. Immunostaining detected the protein levels of lactate dehydrogenase A (LDH-A), pyruvate kinase isozyme M2 (PKM2) and sirtuin 1 (SIRT1) in the ovarian tissues. TNUEL assay was performed to determine cell apoptosis in the PCOS rats. The metabolites in the ovarian tissues were analyzed by liquid chromatography with tandem mass spectrometry. Results: PCOS rats showed an increased in body weight, levels of luteinizing hormone and testosterone and insulin resistance, which was significantly attenuated by the DM treatment. The DM treatment improved disrupted estrous cycle and increased the granulosa cells of the ovary in the PCOS rats. The decreased proliferation and increased cell apoptosis of granulosa cells in the ovarian tissues of PCOS rats were significantly reversed by the DM treatment. The analysis of metabolics revealed that ATP and lactate levels were significantly decreased in PCOS rats, which was recovered by the DM treatment. Furthermore, the expression of LDH-A, PKM2 and SIRT1 was significantly downregulated in ovarian tissues of the PCOS rats; while the DM treatment significantly increased the expression of LDH-A, PKM2 and SIRT1 in the ovarian tissues of the PCOS rats.

show abstract

“…* p < 0.05, ** p < 0.01. S1), which tended to be flat when the sequences number increases to 8,429, showing that the amount of sequencing data were reasonable. The whole composition bacterial community was analyzed using Unweighted-Unifrac of Pcoa ( Fig.…”

Section: Inulin and Metformin Modulated Gut Microbiota In Pcosmentioning

confidence: 90%

“…The severity of insulin resistance and menstrual disorders as well as high levels of androgens in patients with PCOS are closely linked to alteration of gut microbiota [6]. A high fat diet and hyperandrogenic state induce LPS production from abnormal gut microbiota, causing systemic and ovarian inflammation in PCOS [7,8].…”

mentioning

confidence: 99%

Inulin and metformin ameliorate polycystic ovary syndrome <i>via</i> anti-inflammation and modulating gut microbiota in mice

Xue

Liu

et al. 2019

Endocr J

View full text Add to dashboard Cite

Polycystic ovary syndrome (PCOS) represents an endocrine disorder, which is closely related with gut microbiota. Inulin, a kind of probiotics, has been proven to alleviate gut microbiota dysbiosis. Metformin, a biguanide agent, shows beneficial effects on chronic metabolic diseases. Our objective was to assess the effects and associated mechanisms of inulin and metforin on attenuation of PCOS in mice. Mice were divided into 4 groups: control group (CON), model group (MOD), inulin group (INU), metformin group (MET). The last three groups were fed 6 mg of dehydroepiandrosterone (DHEA) per 100 g body weight and 60% high-fat diet to generate mice model. After 21 days of intervention, mice were euthanized and associated indications were investigated. Body weight (BW) and testosterone (T) levels were significantly decreased, but estradiol (E2) levels were increased in INU or MET group, respectively. Ovary HE staining demonstrated that inulin or metformin ameliorated PCOS morphology. Inflammatory indicators from plasma and ovary including TNF-α, IL-6, and IL-17A were decreased in INU or MET group. Moreover, IL-10 in ovary of INU or MET group was increased. Sequencing and analysis of gut microbiota showed that compared to MOD group, Bifidobacterium was increased, but Proteobacteria, Helicobacter and Parasutterella were decreased in INU group. Helicobacter was decreased in MET group. Correlation analysis showed that gut microbiota was correlated with inflammatory factors. Our results revealed that inulin and metformin alleviated PCOS via anti-inflammation and modulating gut microbiota, which may contribute to potential clinical therapy for the disease.

show abstract

Diversity of the Gut Microbiota in Dihydrotestosterone-Induced PCOS Rats and the Pharmacologic Effects of Diane-35, Probiotics, and Berberine

Cited by 75 publications

References 64 publications

Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones—Microbiota—Inflammation Axis in Rats

Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones—Microbiota—Inflammation Axis in Rats

Combined use of Diane-35 and metformin improves the ovulation in the PCOS rat model possibly via regulating glycolysis pathway

Inulin and metformin ameliorate polycystic ovary syndrome <i>via</i> anti-inflammation and modulating gut microbiota in mice

Contact Info

Product

Resources

About