The interplay between PCOS pathology and diet on gut microbiota in a mouse model

Abstract

The gut microbiome has been implicated in polycystic ovary syndrome (PCOS) pathophysiology. PCOS is a disorder with reproductive, endocrine and metabolic irregularities, and several studies report that PCOS is associated with a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, as alterations in macronutrient composition impact the balance of gut microbial communities. This study investigated the interplay between macronutrient balance and PCOS on the gut microbiome of control and dihydrotestosterone (DHT)-induced PCOS-like mice exposed to diets that varied in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha (α) and beta (β) diversity of the gut microbiota of control and PCOS-like mice. However, α-diversity between control and PCOS-like mice on the same diet did not differ significantly. In contrast, β-diversity was significantly altered by PCOS pathology. Further analysis identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) with 99.2% similarity to Bacteroides acidifaciens , which is inversely associated with obesity, to be significantly decreased in PCOS-like mice. Additionally, this study investigated the role of the gut microbiome in the development of PCOS traits, whereby PCOS-like mice were transplanted with healthy fecal microbiota from control mice. Although the PCOS gut microbiome shifted toward that of control mice, PCOS traits were not ameliorated. Overall, these findings demonstrate that while diet exerts a stronger influence over gut microbiota diversity than PCOS pathology, overall gut microbiota composition is affected by PCOS pathology.

Metabolic dysregulation and gut dysbiosis linked to hyperandrogenism in female mice

“…For instance, 6–12 weeks of DHT treatment in pubertal female rats resulted in a shift in beta diversity in addition to an increase in the relative abundance of bacterial taxa including Clostridium , Ruminococcus and Alistipes 54 or Prevotella 55 . Furthermore, 3 months of DHT treatment in pubertal female mice led to a shift in beta diversity, an increase in specific Clostridiales, Proteobacteria and Erysipelotrichaceae bacteria, and a decrease in Bacteroides , Parabacteroides and Porphyromonadaceae 56 . In addition, a study showed changes in beta diversity, an increase in Lactobacillus , and decrease in Bacteroides acidifaciens , Prevotella , S24‐7 and Rikenellaceae species in adult female mice 12 weeks after OVX 57 while another study showed changes in beta diversity, an increase in Allobaculum , Ruminococcus and Methanobrevibacter and a decrease in Prevotella in adult female rats 16 weeks after OVX 58 …”

“…55 Furthermore, 3 months of DHT treatment in pubertal female mice led to a shift in beta diversity, an increase in specific Clostridiales, Proteobacteria and Erysipelotrichaceae bacteria, and a decrease in Bacteroides, Parabacteroides and Porphyromonadaceae. 56 In addition, a study showed changes in beta diversity, an increase in Lactobacillus, and decrease in Bacteroides acidifaciens, Prevotella, S24-7 and Rikenellaceae species in adult female mice 12 weeks F I G U R E 3 Ovariectomy (OVX) and dihydrotestosterone (DHT) treatment alone or in combination resulted in distinct changes in gut microbial community composition of pubertal female mice 2-5 weeks after treatment. Non-metric multidimensional scaling (NMDS) plots were used to visualize differences among the four treatment groups: sham surgery (SHAM) + placebo (P), SHAM + DHT, OVX + P and OVX + DHT.…”

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome

“…In animal experiments, rats with PCOS exert a significant difference in β-diversity (the similarity in gut microbiota composition between various groups) of intestinal microbiota compared with the control but without alteration in α-diversity (gut microbiota richness in one sample). 37 Yang et al found reduced α-diversity of gut microbiota in PCOS participants. 38 Similarly, these alterations in intestinal microbiota were also detected among patients of PCOS in different age groups.…”

“…Many studies have found that PCOS exhibits gut dysbiosis, revealing the strong correlation between PCOS and intestinal microorganisms. In animal experiments, rats with PCOS exert a significant difference in β‐diversity (the similarity in gut microbiota composition between various groups) of intestinal microbiota compared with the control but without alteration in α‐diversity (gut microbiota richness in one sample) 37 . Yang et al found reduced α‐diversity of gut microbiota in PCOS participants 38 .…”

The impact of herbal medicine in regulating intestinal flora on female reproductive disorders

“…Studies have reported that an inextricable link between intestinal flora imbalance and a variety of diseases, such as obesity (Liu et al, 2017a), type 2 diabetes mellitus (T2DM) (He et al, 2022), metabolic syndrome (Woting and Blaut, 2016), inflammatory bowel disease (Ruigrok et al, 2021), chronic heart disease (Hu et al, 2021) and Alzheimer's disease (Jiang Y. et al, 2021). Currently, an increasing number of studies have also shown that intestinal flora played a crucial role in the development and regression of female reproductive endocrine disorders such as polycystic ovary syndrome (PCOS) (Rodriguez Paris et al, 2022), premature ovarian insufficiency (POI) (Jiang L. et al, 2021) and endometriosis (EMs) (Svensson et al, 2021). Intestinal flora is involved in various aspects of female reproduction, including follicle and oocyte maturation, fertilization, embryo migration and implantation, and there is a linear correlation between various intestinal flora and serum sex hormone levels (Qi et al, 2021).…”