Reproductive Endocrinology · Ovarian Hormones

Female reproductive dysfunctions and the gut microbiota

Chadchan SB, Singh V, Kommagani R

Published October 2022 Journal of Molecular Endocrinology
DOI 10.1530/JME-21-0238 PMC PMC10031513

RRM Academy Synopsis

Gut microbiota changes are associated with PCOS and endometriosis

A 2022 review of human and animal studies on endometriosis and polyendocrine metabolic ovarian syndrome (PMOS / PCOS) reports that most studies link altered gut microbiota to these conditions. Few suggest cause and effect. In mice, the fatty acid n-butyrate reduced endometriotic lesion growth.

Key Findings

  • Across the reproductive diseases reviewed, most studies reported associations with altered gut microbial composition, and few suggested cause-effect relationships.
  • A comparison of 102 women with polyendocrine metabolic ovarian syndrome (PMOS), formerly polycystic ovary syndrome (PCOS), and 201 age- and BMI-matched controls identified four bacterial genera that differed.
  • Endometriosis findings diverged: the largest study to date (66 patients, 198 controls) found 12 bacteria at different abundances, while another (35 patients, 24 controls) found no differences.
  • In a rat model of PMOS / PCOS, transplanting fecal microbiota from healthy rats improved estrous cycles in all of the rats (n=8), and Lactobacillus alone improved them in 75%.
  • In mice, altered gut microbiota drove endometriotic lesion growth, and treatment with n-butyrate, a short-chain fatty acid, attenuated lesion growth.

Interpretation

The paper is a review of human microbiome comparisons from stool, saliva and the reproductive tract, together with rodent experiments. Human results for endometriosis differ between studies. The authors list disease stage, age, race and ethnicity, medication and diet as factors for larger studies to assess. They state that no causal link between gut microbiota and endometriosis has been established in humans. Mouse experiments suggest mechanisms, and the authors call for large studies that follow patients over time to learn whether gut imbalance causes these diseases or follows them.

RRM Context

Restorative reproductive medicine looks for the underlying causes of reproductive conditions. The review describes one such pathway, in which gut bacteria help regulate estrogen levels in the blood. The mouse findings on gut-derived fatty acids support larger human studies.

Abstract

The gut microbiome is considered an endocrine organ that can influence distant organs and associated biological pathways. Recent advances suggest that gut microbial homeostasis is essential for reproductive health and that perturbations in the gut microbiota can lead to reproductive pathologies. This review provides an updated overview of the relationship between the gut microbiome and female reproductive diseases. Specifically, we highlight the most recent findings on the gut microbiome in gynecological pathologies including polycystic ovarian syndrome, endometriosis, and endometrial cancer. Most studies revealed associations between altered gut microbial compositions and these reproductive diseases, though few have suggested cause-effect relationships. Future studies should focus on determining the molecular mechanisms underlying associations between gut microbiota and reproductive diseases. Understanding this bidirectional relationship could lead to the development of novel and effective strategies to prevent, diagnose, and treat female reproductive organ-related diseases.

Topics

By this author

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Reproductive Endocrinology › Ovarian Hormones › Estrogen · Menstrual Cycle › Cycle Disorders › Ovulatory Disturbances
Sangappa B Chadchan, Vertika Singh, Ramakrishna Kommagani
S Chadchan, V Singh, R Kommagani
DOI 10.1530/JME-21-0238 10.1530/JME-21-0238 Chadchan et al. 2022, Chadchan 2022