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

Abstract

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.

Effects of Non-insulin Anti-hyperglycemic Agents on Gut Microbiota: A Systematic Review on Human and Animal Studies

“…Fecal specimens of all human studies were analyzed for the composition of gut microbiota. Of 47 mouse studies, 34 studies (72.3%) used fecal samples ( 5 , 6 , 35 , 36 , 38 , 41 , 42 , 44 – 46 , 49 – 56 , 59 – 61 , 63 – 73 , 76 , 78 ). 16S rRNA gene sequencing was the most common method used in human and animal studies ( Table 1 ).…”

“…Among 15 rodent studies ( 5 , 6 , 36 , 37 , 41 , 47 , 48 , 54 , 56 , 58 , 66 , 69 , 70 , 73 , 75 ) on the phylum Firmicutes , the results were inconclusive among those treated with metformin ( 5 , 36 , 37 , 41 , 47 , 48 , 54 , 56 ), acarbose ( 5 , 58 ), liraglutide ( 66 , 69 , 70 ), and sitagliptin ( 5 , 73 ). The genus Lactobacillus was the focus of 13 studies ( 5 , 35 , 41 – 43 , 47 , 53 , 54 , 58 , 62 , 66 , 70 , 73 ).…”

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

“…Moreover, in the genus level, our results showed that FO restored gut dysbiosis in PCOS by up-regulating Lactobacillus, Allobaculum, Desulfovibrio , and Bifidobacterium and down-regulating Actinobacteria and Bacteroides , suggesting that dietary FO attenuated PCOS via restoring the gut dysbiosis. Similarly, dietary prebiotic inulin supplementation ameliorated PCOS in mice via improving the gut microbiota ( 23 ). A recent clinical study found that Bifidobacterium lactis V9 was significantly decreased in patients with PCOS.…”

“…Emerging evidences have demonstrated that the gut microbiota is an essential element in the occurrence and the development of PCOS (23,44). In order to investigate the effect of dietary FO on the composition and the abundance levels of intestinal microbiota in PCOS, fecal samples were detected by 16S rRNA sequencing.…”

“…Gut dysbiosis in PCOS embodies a decrease in alpha diversity, Bifidobcterium, as well as an increase in Bacteroides (21,22). Intriguingly, restoration of gut dysbiosis by dietary prebiotic inulin supplementation contributes to the amelioration of PCOS (23). Regarding VMB, in approximately 70% of healthy women of reproductive ages, predominant Lactobacillus exhibits beneficial effects to the vaginal ecosystem via generating acidic fermentation products (primarily lactic acid) (24,25).…”