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

What was studied?

This study examined the PCOS pathology and diet gut microbiota interplay using a dihydrotestosterone-induced PCOS mouse model to determine how macronutrient balance (protein, carbohydrate, fat) and hyperandrogenism shape gut microbial diversity and composition. The work tested ten controlled diets with varying macronutrient ratios and evaluated their effects on alpha- and beta-diversity, specific taxa abundances, and the extent to which PCOS pathology independently alters microbial structure. The researchers also transplanted fecal microbiota from healthy mice into PCOS-like mice to assess whether restoring a “healthy” microbial community could reverse reproductive or metabolic PCOS traits. This dual-experiment structure allowed clear separation of diet-driven versus PCOS-driven microbial effects, creating a detailed map of how gut microbiota behaves under metabolic, endocrine, and nutritional perturbations in a well-established PCOS model.

Who was studied?

The research used female C57Bl/6J mice, including healthy controls and hyperandrogenic PCOS-like mice generated through continuous dihydrotestosterone exposure beginning in early adolescence. Mice were assigned to one of ten custom diets with precisely formulated protein, carbohydrate, and fat ratios, enabling the investigators to quantify diet-specific microbial responses regardless of PCOS status. In a second experimental arm, PCOS-like mice received either saline or fecal microbiota transplantation after antibiotic gut decontamination to test causal relationships between microbiota composition and PCOS traits. Together, these cohorts provided an internally controlled system linking diet, androgen excess, microbial ecology, and metabolic–reproductive outcomes.

Most important findings

Diet exerted the strongest influence on gut microbiota. Alpha-diversity peaked in diets containing approximately 23% protein, 38% carbohydrate, and 38–48% fat, a macronutrient balance resembling a Mediterranean-style pattern. Beta-diversity also shifted markedly across diets, demonstrating that macronutrient availability reshapes microbial communities at the compositional level. PCOS pathology did not alter alpha-diversity when diet was held constant, but it significantly affected beta-diversity. The most notable microbial signature was a reduction in Bacteroides OTU0003, highly similar (99.2%) to Bacteroides acidifaciens, a species associated with leanness and improved insulin sensitivity. Nine taxa differed significantly between PCOS and control mice, with Bacteroides acidifaciens showing the strongest and most consistent reduction. Carbohydrate intake correlated most strongly with its abundance—higher carbohydrate diets increased B. acidifaciens, suggesting diet-microbe leverage points relevant to metabolic PCOS phenotypes. FMT shifted the PCOS microbiota toward a control-like profile—demonstrated in beta-diversity clustering and normalized abundances of Barnesiella, Parabacteroides, Alistipes, Deltaproteobacteria, and Aestuariispira—but this microbial rescue did not improve adiposity, estrous cycling, ovulation, or hepatic fat deposition.

Key implications

The findings suggest that dietary macronutrient balance dominates gut microbial ecology, outweighing the direct effects of androgen excess. However, PCOS pathology still imprints distinct compositional alterations—especially reduced B. acidifaciens—that may contribute to metabolic dysfunction. The inability of FMT to reverse PCOS traits indicates that hyperandrogenism may drive microbiome-independent mechanisms or that supraphysiologic androgen levels limit microbiota-mediated recovery. Clinically, diets supporting increased microbial diversity and Bacteroides abundance, potentially those emphasizing fiber-rich carbohydrates, may be valuable targets for metabolic improvement in PCOS.

Citation

Rodriguez Paris V, Wong XYD, Solon-Biet SM, et al. The interplay between PCOS pathology and diet on gut microbiota in a mouse model. Gut Microbes. 2022;14(1):2085961. doi:10.1080/19490976.2022.2085961