Guizhi Fuling Wan, Chinese Herbal Medicine, Ameliorates Insulin Sensitivity in PCOS Model Rats With Insulin Resistance via Remodeling Intestinal Homeostasis

Zhu, Ying; Yin, Li; Liu, Min; Hu, Xiaodan; Zhu, Honglin

doi:10.3389/fendo.2020.00575

Cited by 59 publications

(40 citation statements)

References 45 publications

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“…However, Ruminococcaceae_UCG-014 has not been reported. In addition, differences between Lachnospiraceae UCG-008 and Lachnospiraceae_NC2004_group were also revealed at the animal level [19,20]. Therefore, a certain correlation exists between the current research and our results, and the latter can be used as a supplement to study the gut microbiota of PCOS.…”

Section: Discussionsupporting

confidence: 60%

Characteristics of Gut Microbiota and Its Relationship With Serum Sex Hormones in Non-obese Polycystic Ovary Syndrome Patients With Insulin Resistance

Cai¹,

Ni²,

Yao³

et al. 2022

Preprint

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Background: Insulin resistance (IR) is a common symptom in obese polycystic ovary syndrome (PCOS) patients, as well as in non-obese PCOS patients. Gut microbiota is closely related to IR. However, the relationship between gut microbiota and IR remains unclear in non-obese PCOS patients. Objective: To analyze the composition of the gut microbiota population in non-obese PCOS-IR patients compared to PCOS alone and healthy women. Methods: In the present study, fecal samples from non-obese PCOS patients with and without IR and healthy women were analyzed by 16S rRNA gene sequencing. Moreover, serum hormone levels were detected on the third day of menstruation, and the correlation between gut microbiota and serum hormone was analyzed using R language.Results: We found that the gut microbiota character differed in each group, and the gut microbiota abundance of PCOS-IR group was remarkably reduced.The abundance of Ruminococcaceae_UCG-004 and Acetanaerobacterium in the PCOS-IR group was significantly lower than that of the PCOS-NIR group. Furthermore, the comparison between PCOS-IR and control group revealed that g__Fusobacterium and g__Faecalibaculum were the unique genus of the PCOS-IR group. Moreover, the relationship between gut microbiota, IR, and serum sex hormones was determined. In PCOS with IR group, the relationship between gut microbiota and androgen was more significant. In PCOS without IR group, the relationship between gut microbiota and androgen was no significant. Its mechanism may be related to the different abundance in enzymes (futalosine hydrolase, arogenate dehydrogenase (NADP(+), and L-lysine 6-transaminase) and metabolic pathways (isoquinoline alkaloid biosynthesis, styrene degradation, and atrazine degradation), but it needs to be further explored in subsequent experiments. Conclusion: The gut microbiota composition of non-obese PCOS patients with insulin resistance is different from that of PCOS alone and healthy women. The difference is correlated with the clinical characteristics of PCOS, with regards to insulin resistance and sex hormone. The abnormality of gut microbiota may lead to the occurrence and development of PCOS-IR. All in all, this study not only provided supplements for the existing studies, but also revealed the potential pathogenic bacteria genus, thus providing a new idea for the treatment of PCOS with IR.

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Section: Discussionsupporting

confidence: 60%

Characteristics of Gut Microbiota and Its Relationship With Serum Sex Hormones in Non-obese Polycystic Ovary Syndrome Patients With Insulin Resistance

Cai¹,

Ni²,

Yao³

et al. 2022

Preprint

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“…After treatment with β-sitosterol, the structure of the gut microbiota in the PCOS group was significantly changed. Zhu et al ( 28 ) found that the relative abundance of Alloprevotella was decreased significantly in PCOS. However, Bacteroidete-Alloprevotella and Ambiguous_taxa-Alloprevotella were upregulated by β-sitosterol administration, whereas Firmicutes-Lactobacillus, Bacteroidetes-f_Muribaculaceae_ASV_4 , and f_Muribaculaceae_ASV_16 were downregulated.…”

Section: Discussionmentioning

confidence: 99%

“…Researchers have shown that traditional Chinese medicine can improve metabolic disorders by regulating the composition and functional structure of the gut microbiota ( 27 ). For example, Guizhi Fuling Wan as a Chinese herbal medicine could control inflammation by regulating the gut microbiota, and had a certain therapeutic effect on PCOS ( 28 ). This study aimed to explore whether the effect of β-sitosterol in BSYXF on PCOS-like mice is achieved by gut microbiota, so as to provide new therapeutic targets for the treatment of PCOS.…”

Section: Introductionmentioning

confidence: 99%

β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota

Cao

Huang

et al. 2021

Front. Nutr.

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Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota.Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing.Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed.Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.

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“…Recently, accumulating researchers realized that the gut dysbacteriosis is inextricably linked to the onset of the chronic inflammatory diseases, especially PCOS (Insenser et al, 2018;Torres et al, 2018). A large number of animal studies have confirmed the alternation of gut microbiome in PCOS, including a decline in α diversity and the alternation in β diversity (Wang et al, 2020c;Zhu et al, 2020). In clinical studies, females with PCOS also shown extremely different intestinal microbiome compared to healthy controls (Eyupoglu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

et al. 2021

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Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive.Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot.Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells.Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.

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Guizhi Fuling Wan, Chinese Herbal Medicine, Ameliorates Insulin Sensitivity in PCOS Model Rats With Insulin Resistance via Remodeling Intestinal Homeostasis

Cited by 59 publications

References 45 publications

Characteristics of Gut Microbiota and Its Relationship With Serum Sex Hormones in Non-obese Polycystic Ovary Syndrome Patients With Insulin Resistance

Characteristics of Gut Microbiota and Its Relationship With Serum Sex Hormones in Non-obese Polycystic Ovary Syndrome Patients With Insulin Resistance

β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota

Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

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