Microbial Dysbiosis, Infection, and Immunometabolic Signaling in Polyendocrine Metabolic Ovarian Syndrome (Formerly PCOS).
- 1Department of Obstetrics and Gynecology, UT Health San Antonio, San Antonio, TX 78229, USA.
- 2Department of Microbiology, Immunology and Molecular Genetics, UT Health San Antonio, San Antonio, TX 78229, USA.
Abstract
Polyendocrine metabolic ovarian syndrome (PMOS), recently proposed as a new name for polycystic ovary syndrome (PCOS), is a heterogeneous endocrine-metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, and variable ovarian morphology. Low-grade inflammation is common, but its initiating and sustaining factors differ among phenotypes. Microbial communities have emerged as potential modifiers of this inflammatory and metabolic environment. Human studies generally identify differences in gut microbial community structure between affected and unaffected women, although no universal taxonomic signature has been reproduced across regions, phenotypes, or analytic platforms. Mechanistic studies implicate altered intestinal barrier signaling, microbial metabolites, bile acid-interleukin-22 pathways, and immune-cell polarization; however, several influential pathways remain supported principally by animal models. Evidence for lower genital tract dysbiosis is more limited, and apparent associations may reflect hormonal state, menstrual irregularity, adiposity, medications, sexual exposures, or sampling methods. Evidence that specific infections cause PMOS/PCOS is sparse and inconsistent. Small serologic studies involving Chlamydia species and Helicobacter pylori do not establish temporality or causality. This review distinguishes dysbiosis from infection, evaluates human and experimental evidence, and proposes a bidirectional microbial-immune-metabolic-ovarian framework. A focused hypothesis involving interleukin-12-STAT4 signaling is also examined because it provides a specific, testable framework linking microbial or sterile inflammatory signaling to ovarian dysfunction. STAT4 can promote inflammatory T-helper-1 programs and granulosa-cell apoptosis in non-PCOS models, while estrogen can enhance STAT4 activation; nevertheless, direct human PMOS/PCOS evidence is currently absent, and the proposed pathway should not be interpreted as an established disease mechanism. Future studies require deep phenotyping, longitudinal multi-omics, compartment-specific sampling, standardized analysis, and mechanistic validation before microbiome-directed or immune-directed interventions can enter clinical care.
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BibTeX
@article{nevins2026microbial,
title = {{Microbial Dysbiosis, Infection, and Immunometabolic Signaling in Polyendocrine Metabolic Ovarian Syndrome (Formerly PCOS).}},
author = {Allyson Nevins and Nicholas Stansbury and Randal D Robinson and Guangming Zhong},
journal = {Pathogens (Basel, Switzerland)},
year = {2026},
month = sep,
doi = {10.3390/pathogens15101003},
url = {https://europepmc.org/article/MED/42931155},
note = {CC BY},
}
RIS
TY - JOUR
TI - Microbial Dysbiosis, Infection, and Immunometabolic Signaling in Polyendocrine Metabolic Ovarian Syndrome (Formerly PCOS).
AU - Allyson Nevins
AU - Nicholas Stansbury
AU - Randal D Robinson
AU - Guangming Zhong
PY - 2026
DA - 2026/09/22
JO - Pathogens (Basel, Switzerland)
DO - 10.3390/pathogens15101003
UR - https://europepmc.org/article/MED/42931155
AB - Polyendocrine metabolic ovarian syndrome (PMOS), recently proposed as a new name for polycystic ovary syndrome (PCOS), is a heterogeneous endocrine-metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, and variable ovarian morphology. Low-grade inflammation is common, but its initiating and sustaining factors differ among phenotypes. Microbial communities have emerged as potential modifiers of this inflammatory and metabolic environment. Human studies generally identify differences in gut microbial community structure between affected and unaffected women, although no universal taxonomic signature has been reproduced across regions, phenotypes, or analytic platforms. Mechanistic studies implicate altered intestinal barrier signaling, microbial metabolites, bile acid-interleukin-22 pathways, and immune-cell polarization; however, several influential pathways remain supported principally by animal models. Evidence for lower genital tract dysbiosis is more limited, and apparent associations may reflect hormonal state, menstrual irregularity, adiposity, medications, sexual exposures, or sampling methods. Evidence that specific infections cause PMOS/PCOS is sparse and inconsistent. Small serologic studies involving Chlamydia species and Helicobacter pylori do not establish temporality or causality. This review distinguishes dysbiosis from infection, evaluates human and experimental evidence, and proposes a bidirectional microbial-immune-metabolic-ovarian framework. A focused hypothesis involving interleukin-12-STAT4 signaling is also examined because it provides a specific, testable framework linking microbial or sterile inflammatory signaling to ovarian dysfunction. STAT4 can promote inflammatory T-helper-1 programs and granulosa-cell apoptosis in non-PCOS models, while estrogen can enhance STAT4 activation; nevertheless, direct human PMOS/PCOS evidence is currently absent, and the proposed pathway should not be interpreted as an established disease mechanism. Future studies require deep phenotyping, longitudinal multi-omics, compartment-specific sampling, standardized analysis, and mechanistic validation before microbiome-directed or immune-directed interventions can enter clinical care.
SN - 2076-0817
ER -