Recent international evidence-based guidelines for PMOS indicate that lifestyle intervention is fundamental to PMOS management [75], with diet and exercise as critical components. Dietary habits alter gut microbiota and significantly influence weight management, insulin sensitivity, and inflammatory markers [76]. Ketogenic diets improve anthropometric and metabolic indices and sex hormone profiles by reducing insulin, suppressing inflammation, and decreasing fat mass [77]. The Mediterranean diet alleviates chronic inflammation, improves insulin sensitivity, and lowers androgen levels, reducing long-term cardiometabolic and reproductive risks [78].

Various exercise modalities including continuous aerobic exercise, high-intensity interval training, and yoga [79–81]improve cardio-metabolic performance, insulin sensitivity, and menstrual regularity. Exercise combined with dietary management improves HOMA-IR, lipid profiles, BMI, waist circumference, and body fat percentage [82]. However, insufficient data prevent direct comparisons between exercise and dietary therapy or between combined interventions and diet alone.

Despite the well-recognized benefits of lifestyle interventions in improving metabolic and reproductive parameters in women with PMOS, it remains difficult to determine whether such beneficial effects are directly mediated by alterations in gut microbiota composition or function, or indirectly attributed to weight reduction, improved energy metabolism, and reduced systemic inflammation. Most existing studies lack strict control over dietary fiber intake, dietary patterns, physical activity intensity, and other confounding factors, and few investigations adopt microbiota-targeted indicators as primary endpoints. These limitations restrict the mechanistic evidence linking lifestyle modifications to gut microbiota regulation in PMOS management.

Gut microbiota–targeted interventions including fecal microbiota transplantation (FMT), probiotics, and prebiotics have gained attention as potential strategies to restore microbial balance and ameliorate metabolic and reproductive dysfunctions in PMOS. FMT transfers healthy donor fecal material to recipients to address dysbiosis-related disorders [83]. Given the consistent association between gut microbial dysbiosis and the core pathophysiological features of PMOS, reconstruction of a healthy gut microbiota community via FMT represents a theoretically feasible intervention for this syndrome.

A previous study using a DHT-induced PMOS mouse model has shown that FMT from healthy mice effectively modified the gut microbiota composition of PMOS mice, aligning it closer to that of healthy controls. Although FMT did not significantly improve overall PMOS-related phenotypic features, it partially reduced fat accumulation and modified the relative abundance of several metabolism-associated bacteria, including Barnesiella, Parabacteroides, and Alistipes [84]. Another study conducted in letrozole-induced PMOS rats enhanced estrous cyclicity, decreased serum androgen concentrations, reinstated normal ovarian morphological structure, and normalized the composition of gut microbiota [85]. Nevertheless, no clinical trials or human observational studies have yet evaluated the safety and efficacy of FMT in women with PMOS, and all available evidence is restricted to preclinical animal models. As a multisystem endocrine and metabolic disorder, PMOS shares overlapping metabolic disturbances with obesity and type 2 diabetes, conditions in which FMT has shown preliminary therapeutic potential [86]. Therefore, FMT remains a promising exploratory strategy for PMOS management, yet its clinical value cannot be confirmed until rigorous human studies are performed.

Similarly, probiotics, defined as “live microorganisms that, when administered in adequate amounts, confer health benefits on the host”, have attracted extensive attention for their potential to ameliorate metabolic and endocrine disorders in PMOS [87]. Accumulating evidence indicates that probiotics improve metabolic profiles and attenuate IR by promoting the production of SCFAs, regulating inflammatory and oxidative stress pathways, and inhibiting the release of proinflammatory cytokines [88]. The probiotic strains with documented beneficial effects in PMOS models mainly belong to the genera Bifidobacterium, Lactobacillus, Clostridium, Enterococcus, and other lactic acid bacteria [89]. Research indicates that Bifidobacterium longum subsp. Longum BL21 can mitigate PMOS by enhancing hormonal levels in PMOS mice via the brain-gut-ovary axis, curtailing weight gain, diminishing inflammatory markers, and optimizing microbial composition. However, this study did not fully elucidate the interactive mechanisms among dietary metabolism, gut microbiota, and PMOS pathogenesis [90].

He et al. [91] employed a letrozole-induced PMOS rat model to systematically evaluate the therapeutic effects of eight lactic acid bacterial strains. The results showed that Lactobacillus plantarum HL2 and Bifidobacterium longum HB3 significantly ameliorated ovarian pathological alterations, diminished testosterone levels, and partially restored LH, FSH, and their abnormal ratios. Furthermore, these strains modulated gut microbiota associated with sex hormones, including Akkermansia, Prevotella, and Staphylococcus.

Prebiotics are specialized substrates that are selectively utilized by host microorganisms and confer beneficial effects on host health [87]. Indigenous intestinal microorganisms ferment prebiotics to produce bioactive metabolites, among which oligofructose and oligogalactose are the most widely studied for their health-promoting properties [92]. Certain studies indicate that prebiotics can mitigate hyperandrogenism, enhance insulin sensitivity, and lower cardiometabolic risk by fostering the synthesis of SCFAs in the colon, ameliorating inflammatory conditions, and optimizing energy metabolism [93].

Animal studies have shown that inulin supplementation improves glucose tolerance, insulin sensitivity, and ovarian morphology in PMOS models, while reducing serum testosterone, AMH, and LH levels. These effects were accompanied by increased abundance of SCFA-producing bacteria, enhanced acetate, propionate, and butyrate production, improved intestinal barrier function, and suppression of inflammatory mediators such as IL-1β, IL-18, and LBP. A clinical investigation including women with PMOS has shown that supplementation with 10 g of inulin over three consecutive months improved hyperandrogenism, IR, and dyslipidemia, while increasing Bifidobacterium abundance and decreasing Escherichia coli and Shigella levels [27]. A further investigation assessed the impact of resistant dextrin on enhancing metabolic indices, androgen levels, and clinical symptoms, including hirsutism and menstrual cycle abnormalities, in women with PMOS [94].

Based on current evidence from animal models and limited human studies, gut microbiota–targeted interventions—including fecal microbiota transplantation, probiotics, and prebiotics—are more likely to exert adjunctive therapeutic effects in PMOS by improving the metabolic and inflammatory microenvironment, rather than serving as independent or definitive treatment modalities. Although the observed beneficial effects provide indirect support for the causal involvement of gut microbiota in PMOS pathophysiology, the stability, efficacy reproducibility, and clinical generalizability of these interventions remain to be validated through well-designed, large-sample, and long-term randomized controlled trials with strict phenotypic stratification. A recent systematic review and meta-analysis of randomized controlled trials further suggested that microbiota-related interventions may improve several metabolic, hormonal, and inflammatory outcomes, but heterogeneity in intervention type, duration, and outcome definitions remains an important limitation [95].

Natural plant-derived compounds, including polyphenols and traditional Chinese medicines (TCM) show considerable potential in modulating gut microbiota composition, alleviating inflammation, and improving metabolic and endocrine disturbances in PMOS. These substances promote beneficial bacteria, restore homeostasis, and attenuate systemic inflammation, contributing to improved hormonal balance, insulin sensitivity, and lipid metabolism [96]. Polyphenols are a large class of plant secondary metabolites, mainly including resveratrol, anthocyanins, catechins and other components. Numerous studies indicate that resveratrol enhances insulin sensitivity by activating SIRT1/AMPK and PI3K/Akt signaling pathways [97, 98], modulates PPAR-γ and lipid metabolism-related variables, and mitigates dyslipidemia. Simultaneously, resveratrol can reduce androgen synthesis by inhibiting the activities of CYP17A1 and HMG-CoA reductase [99]. In addition, resveratrol can improve chronic low-grade inflammation by blocking NF-κB and VEGF signaling pathways, and restore normal ovulatory function and follicle morphology [100]. Notably, resveratrol also exerts a prebiotic-like effect, which can improve gut microbiota dysbiosis associated with PMOS, thus indirectly alleviating metabolic disorders. Although the safety of resveratrol in vivo is satisfactory, its clinical efficacy as an adjuvant therapy for PMOS still needs to be confirmed by high-quality randomized controlled trials [99].

Anthocyanins have been proved to improve ovarian steroid hormone imbalance in androgen-induced PMOS mice, regulate steroid synthase and antioxidant enzyme levels, and address inflammatory marker abnormalities, demonstrating potential therapeutic effects [101]. Research indicates that catechins in oolong tea can improve ovarian dysfunction and insulin resistance in PMOS mice by inhibiting the p-STAT3 signaling pathway, reduce uterine inflammation and matrix degradation [102]. Green tea is abundant in catechins, and green tea extract can enhance IR and ovarian morphology in PMOS model rats while decreasing testosterone levels [103].

Traditional Chinese medicine has gradually formed a unique therapeutic system for PMOS under long-term clinical practice. This system is guided by the holistic view and treatment based on syndrome differentiation, and has the characteristics of multi-target and multi-pathway regulation. A large number of studies have confirmed that TCM can significantly ameliorate endocrine disorders in PMOS patients by regulating ovarian blood flow dynamics, improving serum hormone levels and normalizing menstrual cycles, so as to increase ovulation rate and clinical pregnancy rate.

In recent years, the regulatory effect of TCM and its components on gut microbiota has been gradually revealed. Studies have shown that Bailing capsule can improve ovarian dysfunction, reduce IR, and enhance sex hormone levels in mice with PMOS. BL modulates the intestinal microbiota and inflammatory response in PMOS model mice. Bailing capsule can improve gut microbiota disturbance and inflammatory response in PMOS mice by regulating LPS-TLR4 inflammatory pathway [104]. Other TCM formulations, including HeQi San, Bu Shen Hua Zhuo formula, Zishen Qingre Lishi Huayu formulation, and Yulin Tong Bu compound, have also been shown to alleviate PMOS-like phenotypes in animal or clinical studies by improving ovarian function, enhancing insulin sensitivity, increasing gut microbiota diversity, and enriching beneficial and SCFA-producing bacteria [105–108].

In terms of single component of TCM, berberine, an isoquinoline alkaloid derived from Coptis chinensis, can successfully restore the diversity and structure of gut microbiota, regulate microbial metabolites, and ameliorate gut microbial imbalance in patients with PMOS [109]. Research indicates that quercetin can systematically lower insulin, blood glucose, cholesterol, and TG levels, modulate pituitary-ovarian axis function, mitigate oxidative stress damage associated with PMOS, manage the metabolic environment of patients, and treat PMOS symptoms [110].

Overall, polyphenols and TCM can improve PMOS through multi-dimensional pathways such as restoring gut microbiota balance, ameliorating metabolic dysfunction and suppressing inflammatory responses, showing comprehensive therapeutic potential. However, it is worth noting that current evidence that natural plant compounds and traditional Chinese medicines for improve PMOS by regulating gut microbiota is still mainly from animal experiments. The key molecular targets, the dependence of therapeutic effects on gut microbiota, and the exact clinical benefits in humans still need to be further clarified. Therefore, such interventions are still at the exploratory and adjunctive therapeutic level, and cannot be used as the first-line and definitive treatment for PMOS. In the future, more in-depth mechanism studies and large-sample, long-term clinical trials are needed to clarify the molecular targets, efficacy and safety of these compounds, so as to promote their clinical transformation and application.

PMOS patients with insulin resistance are accompanied by impaired insulin receptor-related signaling pathways, which will be further aggravated by obesity and its related phenotypes such as visceral fat accumulation, chronic inflammation and oxidative stress response. Metformin and GLP-1 receptor agonists can not only induce therapeutic effects via weight reduction but also influence the mechanisms underlying IR, potentially serving as useful treatment alternatives for obese patients with PMOS.

Among these agents, metformin can decrease weight, enhance insulin sensitivity, regulate menstrual cycle and reduce androgen level [111]. In recent years, the regulatory effect of metformin on gut microbiota has attracted increasing attention. Research indicates that metformin can improve metabolic disorders and restore ovulatory function in PMOS rats by activating intestinal AMPK, regulating gut microbiota and increasing the production of beneficial metabolites such as I3A [112]. Clinical studies have confirmed that metformin treatment can effectively reduce body fat rate and visceral fat content in PMOS patients, and improve IR and persistent low-grade inflammation.

Simultaneously, metformin can enhance Akkermansia muciniphila, Clostridium leptum group, Faecalibacterium prausnitzii and other beneficial bacteria, reduce the proportion of harmful bacteria, and rebuild the structure of gut microbiota. Xue et al. [113] discovered that metformin can mitigate PMOS by regulating gut microbiota, decreasing plasma LPS levels, and lowering the concentration of inflammatory mediators, including tumor necrosis factor α, interleukin 6, and interleukin 17A, in individuals with PMOS. Significantly, metformin treatment may normalize altered fecal SCFA levels in patients with PMOS, suggesting that metformin can improve intestinal microenvironment by regulating SCFA metabolism [114]. Nonetheless, metformin is prone to gastrointestinal adverse reactions, which limits the long-term medication compliance of patients.

The weight-loss and metabolic enhancement benefits of GLP-1 receptor agonists provide unique potential for expanding the treatment options of PMOS. Semaglutide can reestablish the movement rhythm of PMOS mice via the PI3K/AKT/mTOR pathway, rectify serum hormone imbalances, enhance glucose tolerance, and mitigate autophagy and ovarian oxidative damage in PMOS animals [115]. Semaglutide can also reduce ovarian tissue inflammation and enhance PMOS phenotype through AMPK/SIRT1/NF-κB signaling pathway [116].

In a clinical study, 3 mg liraglutide was given daily to obese and non-diabetic PMOS women for 32 consecutive days. After short-term treatment, improvements in body weight, hyperandrogenism and menstrual cyclicity were observed [117]. Exenatide combined with metformin has a good effect in reducing body weight, decreasing BMI and waist circumference, and improving blood glucose and insulin sensitivity in overweight or obese PMOS women, with acceptable short-term adverse reactions [118]. Nonetheless, the precise mechanism of GLP-1 receptor agonists in improving metabolic and reproductive abnormalities related to PMOS is still not fully elucidated, and most of the existing studies lack long-term follow-up data. The persistence of weight-loss effect and the long-term metabolic benefit of GLP-1 receptor agonists still need more clinical verification [119].

Orlistat plays an anti-obesity role by inhibiting gastrointestinal lipases and reducing the absorption of dietary fat. Current randomized controlled trial data confirm that orlistat has a certain effect in reducing weight, decreasing HOMA-IR index, insulin level and testosterone concentration in PMOS patients, but the incidence of adverse reactions related to orlistat is high [120].

Metformin, GLP-1 receptor agonists, orlistat and other hypoglycemic and weight-loss drugs have been confirmed to reduce body weight, improve insulin sensitivity and normalize metabolic disorders, so they provide feasible treatment choices for obese PMOS patients.

Although various pharmacological treatments will be accompanied by alterations in gut microbiota composition and function, it remains difficult to distinguish the extent to which these changes directly mediate therapeutic effect, or are the secondary consequences of improved metabolism and weight loss. In this context, gut microbiota is more likely to serve a dual role as both a mediator of treatment effects and a responsive biomarker.

Despite the comprehensive synthesis of evidence regarding the associations among gut microbiota, microbial metabolites, and PMOS, this narrative review and the underlying primary literature have several notable limitations that should be acknowledged.

At the review level, although this article adopted a systematic literature search strategy, it remains a narrative review rather than a formal scoping review or systematic review. Therefore, the evidence synthesis may still be influenced by narrative interpretation and selection heterogeneity. To address this concern, detailed information on database sources, search time frame, keyword strategies, inclusion and exclusion criteria, as well as the study selection process has been supplemented in the revised manuscript to enhance methodological rigor and transparency.

At the primary research level, most of the included studies are observational or cross-sectional in design, with a scarcity of large-scale randomized controlled trials and long-term prospective cohort data. Consequently, the causal inference linking gut microbiota dysbiosis to the onset and progression of PMOS remains weak, and most conclusions are restricted to associative relationships rather than definitive causal pathways.

In addition, substantial heterogeneity exists across included studies in terms of microbial detection techniques, with some studies using 16S rRNA gene sequencing and others adopting metagenomic or metabolomic approaches. Study populations differ significantly in ethnicity, obesity status, age, and PMOS phenotypic classification, and the application of Rotterdam criteria also varies across research centers. These inconsistencies contribute to divergent microbial signatures and metabolic profiles, limiting cross-study comparability and the generalizability of conclusions.

Mechanistically, most studies focus on correlative analysis between microbial alterations and clinical phenotypes, whereas detailed and validated signaling pathways through which key microbial metabolites regulate insulin sensitivity, androgen synthesis, inflammatory responses, and ovarian function remain insufficiently clarified. The functional validation of specific bacterial genera and critical metabolites is mostly derived from animal models, lacking direct and reliable evidence in humans.

Finally, most microbiota-targeted interventions, including probiotics, prebiotics, fecal microbiota transplantation, natural compounds, and related pharmacological agents, are supported by preclinical experiments or small-scale preliminary clinical trials. Issues such as optimal strain selection, therapeutic dosage, intervention duration, clinical reproducibility, long-term efficacy, and safety profiles have not been systematically elucidated, hindering the translation of microbiota-based strategies into routine clinical practice for PMOS.

In summary, accumulating evidence indicates that gut microbiota and PMOS are linked through complex and tightly interconnected interactions, with gut microbial dysbiosis emerging as a critical regulatory node bridging metabolic abnormalities, endocrine dysfunction, and ovarian impairment. During the onset and progression of PMOS, alterations in gut microbiota may contribute to the development of core phenotypes, including insulin resistance, hyperandrogenism, and obesity, by modulating insulin sensitivity, chronic low-grade inflammation, and androgen homeostasis. An increasing body of evidence further suggests that microbiota-derived metabolites act as key mediators in gut microbiota-host interactions. Through the regulation of metabolic pathways, immune responses, and endocrine signaling networks, these metabolites collectively drive the pathophysiological changes associated with PMOS. Microbiota-targeted interventions have shown promising potential in improving metabolic and endocrine outcomes; however, their underlying mechanisms, causal relevance, and clinical benefits remain to be fully elucidated.

This narrative review was performed using a systematic and transparent literature search strategy with well-defined database sources, search terms, time frame, and rigorous inclusion and exclusion criteria, which greatly improved the methodological reliability and quality of evidence synthesis. Future research should therefore prioritize well-designed studies with clearly defined disease phenotypes, integrating longitudinal follow-up, causal inference approaches, and multi-omics analyses to systematically delineate the key regulatory pathways through which gut microbiota and their metabolites contribute to PMOS. As understanding of the gut–metabolism–endocrine–ovary axis continues to advance, precision intervention strategies based on individual gut microbiota characteristics may offer new theoretical foundations and therapeutic directions for the long-term management of PMOS and the improvement of overall patient health outcomes.