Gut microbiota composition linked to PCOS subtypes: regional and testosterone-based variations found

By Dr. Priyom Bose, Ph.D.Reviewed by Lily Ramsey, LLMOct 22 2024

The gut microbiota composition is distinct in patients with polycystic ovary syndrome (PCOS), relative to healthy control (HC); however, no significant difference was noted in alpha-diversity, the study finds.

Study: Gut microbiota in women with polycystic ovary syndrome: an individual based analysis of publicly available data. Image Credit: NTshutterth/Shutterstock.com

A recent eClinicalMedicine study considered publicly available data to explore the characteristics of gut microbiota in PCOS patients and whether it helps distinguish different PCOS subtypes.

Polycystic ovary syndrome and gut microbiota

PCOS is a reproductive endocrine disorder that is characterized by polycystic ovarian morphology injury, increased androgen, hirsutism, ovulatory dysfunction, and/or acne.

It poses a considerable burden on public health systems and patients. The precise pathology and etiology of PCOS remain unclear. Additionally, available therapies are often inadequate for many patients owing to the heterogeneity of clinical phenotypes.

The human gut microbiota influences the development of various diseases, such as PCOS. Research has shown that PCOS patients have lower levels of Bacteroidota phylum and Bacteroidaceae, Porphyromonadaceae family, and higher levels of Streptococcaceae family and Bacteroidota phylum. For the treatment of PCOS, bile acid metabolism mediated by the gut microbiota is crucial.

Overall, the results documented in the literature have not highlighted specific changes in bacteria due to heterogeneity in gut microbiota research. Additionally, a causal relationship between PCOS and gut microbiota has not been established.

Furthermore, regional heterogeneity among PCOS patients heterogeneity concerning testosterone levels has not been fully understood.

About the study

To address the gaps in the literature mentioned above, the current study synthesized existing evidence on the gut microbiota composition of PCOS patients. By detecting gut microbiota patterns in PCOS subtypes, potential microbial biomarkers for PCOS subtypes were identified. The possible reasons for individual variation in PCOS treatment were also proposed.

Four electronic databases, namely, PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov, were searched from Jan 1, 2010, to May 1, 2024.

The studies consisted of raw data on the gut microbiota of PCOS patients. There were no restrictions on the region or language of publication, and unpublished studies were excluded from the study. Gut microbiota analysis was conducted across regions and different testosterone levels.

Study findings

Following rigorous screening, 14 cohort studies were considered for analysis. Three were conducted in Austria, Poland, and Russia, and eleven were conducted in China. The total sample consisted of 513 PCOS patients and 435 healthy controls, with ages ranging between 23 and 35. Across several studies, testosterone levels were significantly higher in PCOS patients relative to HC.

Phylum level analysis showed reduced Bacillota and increased Actinobacteriota in PCOS patients. At the genus level, among PCOS women, Bacteroides, Blautia, and Bifidobacterium were marginally higher, while Ruminococcus was reduced.

Further characterization noted the upregulation of 4 genera and downregulation of 12 genera in PCOS patients. Mesomycoplasma, Bacteroides, Bifidobacterium, Ruminococcus_gnavus_group, Bilophila, Blautia, Eggerthella, and Butyricicoccus were increased in the PCOS group.

Holdemanella, Mucispirillum, Ruminococcus, Christensenellaceae_R-7_group, UCG-002, UCG-005, Clostridia_UCG-014, Rikenellaceae_RC9_gut_ group, Desulfosarcina, Millionella, Lachnospiraceae_UCG-008, Desulfosarcina, and UCG010 were decreased. Blautia was identified in both HC and PCOS individuals.

In Chinese PCOS patients, alpha diversity showed a marked decrease, while an increase was noted in European patients. Among the Chinese, Actinobacteriota, Bacteroidota, and Proteobacteriota were more enriched. Bifidobacterium genus and Actinobacteriota phylum were more abundant as well.

Faecalibacterium was decreased in the European cohort. The specific bacteria characteristic of PCOS patients were also seen to vary distinctly across regions.

In Chinese PCOS patients, the key taxa Gemmiger, Faecalibacterium, Burkholderia, and Duncaniella in HC individuals were altered. In European networks, the key taxa showed minimal changes.

Across testosterone levels, the structure of gut microbiota differed, but there was no significant difference in alpha diversity. Prevotella and Phocaeicola were more common in high testosterone (HT) patients, who also showed reduced Alistipes, Agathobacter, Barnesiella, Faecalibacterium, and Ruminococcus. Faecalibacterium, Bacteroides, Prevotella, Incertae_Sedis, and Dialister were key taxons in PCOS patients with lower testosterone (LT).

Eighteen genera in the PCOS-HT group helped distinguish PCOS-HT from HC. Across the HT and LT groups, the elaborate correlations of the key taxon were distinct. The intestinal environment of PCOS patients with HT expanded the presence of genera like Phocaeicola, Dialister, Prevotella, and Ruminococcus_torques_group. Bifidobacterium, Faecalibacterium, Eubacterium_eligens_group, and Alistipes were diminished.

Concerning the potential mechanism of gut microbiota causing PCOS, it was noted that PCOS patients with HT who had enriched Prevotella and Dialister possessed unique gene combinations than Blautia, Faecalibacterium, and Bacteroides.

One potential reason why PCOS patients with HT differ from LT patients could be the annotation of more lipopolysaccharide biosynthesis by Dialister, relative to other strains.

Conclusions

In summary, this combined analysis showed the difference in gut microbiota between European and Chinese PCOS patients. Gut microbiota also showed the potential to differentiate among PCOS patients with different levels of testosterone.