Association between changes in gut microbiome and mental health indicators in PCOS: Study

Women with PCOS have an increased risk of depression, anxiety, and eating disorders, such as binge eating disorder and bulimia. Factors like stress, inflammation, insulin, satiety hormones, serotonin, and dopamine control the function of the hypothalamus and affect PCOS symptoms, mood, and eating behavior. Active research is ongoing to understand the cause and pathogenesis of PCOS, and recent years have provided a growing body of evidence of the role of the gut microbiota in PCOS. Within the human gastrointestinal tract resides the gut microbiota, a highly diverse and intricate microbial ecosystem that has evolved in concert with its host over time. It is estimated that the human gut contains approximately 100 trillion bacterial cells that comprise over 400 species, accounting for roughly 78% of the total human microbiota. This microbial community contributes to various functions in the gut, such as vitamin and nutrient synthesis, carbohydrate fermentation, immune regulation, and protection against pathogens.

Because of the extensive bidirectional communication between these microorganisms and the host, particularly involving the enteric nervous system (ENS) and neuroimmune pathways, the gut microbiota is frequently referred to as the ‘‘second brain’’. The communication network between the central nervous system (CNS) and the intestine is called the ‘‘gut–brain axis’’ (GBA). The gut microbiota communicates with the brain, directly or indirectly, through three major information systems: neural messaging by the ENS and vagal neurons, immune messages carried by cytokines, and endocrine messages relayed by hormones. The microbiota produces many directly neuroactive compounds, like neurotransmitters (gamma-aminobutyric acid [GABA], noradrenaline, serotonin, dopamine) and other microbial metabolites (short-chain fatty acids [SCFAs], secondary bile acids). These factors can either be secreted into the portal circulation or locally affect the neuronal cells of the ENS and afferent pathways of the vagus nerve. Through these signals, the microbiota regulates absorption, immunity, and satiety, as well as neuronal processes.

Currently, the interplay between the gut microbiome, mental health, and PCOS is not fully understood. In PCOS,microbial imbalances may contribute to inflammation and metabolic dysfunction, although causal links remain unclear. Certain microbial taxa, such as Bacteroidetes that are associated with proinflammatory responses, are more prevalent in PCOS, whereas beneficial genera like Prevotella appear to be reduced. Notably, these same bacteria are also implicated in regulating mental health. Similar patterns of dysbiosis, reduced beneficial bacteria, and increased proinflammatory species are also observed in mood disorders. This overlap suggests that targeting the gut microbiome may offer a novel, integrative approach to managing both metabolic and mental health aspects of PCOS. On this basis, authors aimed to systematically gather information on the microbiome studies in association with mental health in women with PCOS. By collecting the current knowledge in the field, we propose different mechanisms linking the gut, brain, and PCOS.

A comprehensive literature search across the PubMed database until July 2025. Studies were included if they met the following criteria: observational/intervention studies; assessing microbiome through 16S ribosomal ribonucleic acid amplicon/ 16S ribosomal ribonucleic acid gene sequencing/metagenomics; comparing microbiome between women with and without PCOS; published from 2007 until 2025, and articles available online.

A total of 159 studies were identified and screened for title, abstract, and full text. Eight studies met the criteria (2 rodent, 6 human studies). The quality assessment indicated that half of the studies(4/8) presented a high risk of bias. Regardless of the limited number of studies and the low quality scores, all the studies highlighted the association of the gut microbiome in PCOS with mental health problems.

Microbes play an important role in human health and disease, and their link with PCOS and concurrent mental health problems is gaining support. Current studies on the gut–brain mental health axis in women with PCOS should, however, be considered preliminary, and further mechanistic studies are warranted. These first studies conducted possess various limitations, such as a low number of participants, different criteria for disease diagnosis, differences in age, ethnicity, use of different types of medication, BMI, as well as other noncontrolled variables (i.e., nutrition, lifestyle habits) that need to be considered for well-designed microbiome studies. The quality assessment of the published studies highlights that half of the studies lack rigorous study design, particularly properly matched cases and controls, the use of the same criteria for identification of study groups, the exposure measures the same way for cases and controls, and the assessment of study outcomes in a standard, valid, and reliable way for all study groups.

Regardless of these shortcomings, the first studies in the field are suggesting the association of the gut bacteria and mental health in women with PCOS, where Gram-negative bacteria seem to prevail and Gram-positive bacteria are less prevalent than in controls. Gram-negative bacteria are known to trigger inflammatory processes, which might be one possible mechanism linking microbiome and mental disorders in women suffering from PCOS. In this review, authors have summarized the first findings in the field and proposed different regulatory mechanisms. Nevertheless, more research is needed with a bigger sample size across various ethnicities and age groups, and should move from descriptive studies to mechanistic approaches to understand the exact mechanisms by which microbes modulate their actions. Once the molecular routes are established, the modulation of the microenvironment in the gut with the aim to alleviate and improve PCOS symptoms, together with potential treatment possibilities for this common metabolic disorder, could be developed.

Source: Riikka K. Arffman, Barbara A. Folch, Irene Leones-Ba nos;

Fertil Steril® Vol. 124, No. 5P2, November 2025 0015-0282