Effect of High-Fat Diet  on  the Intestinal Flora in Letrozole-Induced Polycystic Ovary Syndrome Rats

Abstract

Aim. The aim of this study was to explore whether letrozole and high-fat diets (HFD) can induce obese insulin-resistant polycystic ovary syndrome (PCOS) with intestinal flora dysbiosis in a rat model. We compared the changes in the intestinal flora of letrozole-induced rats fed with HFD or normal chow, to explore the effects of HFD and letrozole independently and synergistically on the intestinal flora. Methods. Five-week-old female Sprague Dawley (SD) rats were divided into four groups: control (C) group fed with regular diet; L1 group administered with letrozole and fed with regular diet; L2 group received letrozole and fed with HFD; and HFD group fed with HFD. At the end of the experiment, ovarian morphology, hormones, metabolism, oxidative stress, and inflammatory status of all rats were studied. 16S rDNA high-throughput sequencing was used to profile microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. Results. Compared to the C group, the increased plasma fasting insulin and glucose, HOMA-IR, triglyceride, testosterone, and malondialdehyde were significantly higher in the L2 group, while high-density lipoprotein cholesterol was significantly lower in the L1 group and L2 group. The indices of Chao1 and the Abundance-based Coverage Estimator (ACE) (α-diversity) in the L2 and HFD groups were significantly lower than that in the C group. Bray–Curtis dissimilarity based principal coordinate analysis (PCoA) plots and analysis of similarities (ANOSIM) test showed obvious separations between the L2 group and C group, between the HFD group and C group, and between the L2 and HFD groups. At the phylum level, Firmicutes and ratio of Firmicutes and Bacteroidetes (F/B ratio) were increased in the L2 group; Bacteroidetes was decreased in the L2 and HFD groups. No significant differences in bacterial abundance between the C group and L1 group were observed at the phylum level. Based on linear discriminant analysis (LDA) effect size (LEfSe) analysis, the bacterial genera (the relative abundance > 0.1%, LDA > 3, p < 0.05 ) were selected as candidate bacterial signatures. They showed that the abundance of Vibrio was significantly increased in the L1 group; Bacteroides and Phascolarctobacterium were enriched in the HFD group, and Bacteroides, Phascolarctobacterium, Blautia, Parabacteroides, Akkermansia [Ruminococcus]_torques_group, and Anaerotruncus were enriched in the L2 group. Conclusion. The effect of letrozole on intestinal flora was not significant as HFD. HFD could destroy the balance of intestinal flora and aggravate the intestinal flora dysbiosis in PCOS. Letrozole-induced rats fed with HFD have many characteristics like human PCOS, including some metabolic disorders and intestinal flora dysbiosis. The dysbiosis was characterized by an increased Firmicutes/Bacteroidetes ratio, an expansion of Firmicutes, a contraction of Bacteroidetes, and the decreased microbial richness. Beta-diversity also showed significant differences in intestinal microflora, compared with control rats.

Modified Banxia Xiexin Decoction Ameliorates Polycystic Ovarian Syndrome With Insulin Resistance by Regulating Intestinal Microbiota

“…Previous studies have shown that Akkermansia can reduce the body weight and total cholesterol of obese patients, increase insulin sensitivity, improve IR, and reduce inflammatory reaction ( Shin et al., 2014 ; Dao et al., 2016 ; Depommier et al., 2019 ), and its mechanism may be adjusting the thickness of intestinal mucosa and maintaining the integrity of intestinal barrier ( Derrien et al., 2004 ). As a potential probiotic, Blautia was significantly enriched in the treatment group, and it was proved to play certain roles in metabolic diseases, inflammatory diseases, and biotransformation ( Eren et al., 2015 ; Liu et al., 2021 ; Zheng et al., 2021 ). Meanwhile, Clostridium_sensu_stricto_1 , which was thought to cause inflammation and lead to severe intestinal infections ( Fletcher et al., 2021 ), was significantly higher in the model group and significantly lower in the treatment group.…”

“…(2020) also found that α-diversity in PCOS-IR model rats had an increasing trend. As we all know, diet is one of the most important environmental factors that change the structure of the microbiota ( David et al., 2014 ; Zheng et al., 2021 ). Whether the increase in α-diversity was caused by a high-fat diet or a rising proportion of harmful bacteria needs further study.…”

Differential expression of serum mir-363-3p in patients with polycystic ovary syndrome and its predictive value for their pregnancy

“…There are several limitations in this study that need to be explored. First, studies have found that inflammatory reaction is significantly correlated with the occurrence and development of PCOS [ 27 , 28 ]. This study did not analyze the inflammatory indicators of the subjects, so the relationship between miR-363-3p and inflammation cannot be verified for the time being.…”

Present and Future: Crosstalks Between Polycystic Ovary Syndrome and Gut Metabolites Relating to Gut Microbiota

“…Numerous patients with PCOS have bad habits, such as an adoration of sweets, a love of fat, an absence of dietary fiber, and little exercise, which affects gut health ( 18 , 78 ). A high-fat diet (HFD) was linked to an increase in the pro-inflammatory microbiota, such as Clostridiales , Bacteroides , and Enterobacteriales , and a decrease in the anti-inflammatory microbiota, such as Lactobacillus , in the rat ( 75 ).…”

“…Interestingly, the activity and contents of gut metabolites can be regulated by the gut microbiota ( 18 , 19 ). The correlations between gut metabolites and gut microbiota have been demonstrated in numerous metabolic diseases, such as obesity, type 2 diabetes, NAFLD, and cardiovascular diseases ( 20 , 21 ).…”