Breast cancer (BC) is the most prevalent cancer among women globally and remains a leading cause of cancer-related morbidity and mortality, despite significant advancements in early detection and treatment (1). Innovations such as advanced imaging techniques, minimally invasive surgeries, targeted therapies, immunotherapies, personalized medicine, radiation therapy, and multidisciplinary approaches have contributed to improved survival outcomes (2). However, approximately 20-30% of women diagnosed with early-stage BC, depending on the subtype, experience recurrence, often manifesting as metastatic disease (3, 4). This highlights the critical need for enhanced early detection strategies and innovative prognostic tools to improve therapeutic efficacy and survival outcomes.

Emerging evidence highlights the pivotal role of the gut microbiome in several cancers, including BC, where dysbiosis has been implicated in disease initiation, progression, and therapeutic response (5–9). Current evidence suggests that the gut microbiome influences BC risk by modulating systemic estrogen levels (10), metabolite production (11), and inflammatory responses. Elevated estrogen levels are well-documented risk factors for BC, with β-glucuronidase enzymes produced by certain gut bacteria facilitating estrogen reabsorption into the bloodstream, thereby contributing to BC pathogenesis (10, 12). Recent mechanistic studies also demonstrate that gut microbiota can regulate steroid hormone activity, immune modulation, and therapeutic response in BC, further underscoring their potential role as biomarkers and therapeutic targets (7, 13–15).

Several reviews have investigated the relationship between gut microbiome composition and BC. A systematic review of 10 case studies reported that BC patients exhibit decreased relative abundance of beneficial bacteria such as Prevotellaceae, Ruminococcus, Roseburia inulinivorans, and Faecalibacterium prausnitzii, alongside increased abundance of Bacteroides and Erysipelotrichaceae (16). However, findings across studies remain inconsistent, with variability linked to cancer stage, molecular subtype (11, 17, 18), menopausal status (10, 19), ethnicity, body mass index (20), diet (13), and medication use (21). Moreover, although prior reviews have highlighted mechanistic links between microbiota, estrogen metabolism, and BC progression, they have not adequately addressed how these associations may differ across geographical regions. This review, therefore, aims to fill this gap by synthesizing evidence on gut microbiome variations in BC across China, the USA, and Europe. By critically examining geographical differences, we seek to identify consistent microbial signatures, evaluate their potential as predictive biomarkers (22), and highlight directions for future research. Ultimately, this analysis may contribute to the development of microbiome-informed strategies that support personalized approaches to BC management.

We performed a mini-review of the literature through structured searches of PubMed, Medline, and ScienceDirect from database inception through December 2024. The search strategy included the terms “gut microbiome,” “gut microbiota,” “breast cancer,” and related synonyms. Reference lists of eligible articles were also screened. Eligible studies were peer-reviewed, English-language, human case–control studies comparing gut microbiome composition in adult women with BC and healthy controls. We excluded animal and preclinical studies, reviews, editorials, conference abstracts, and non-English publications. Data extracted from each study included participant characteristics, geographic setting, sequencing platform, measures of microbial diversity, and taxonomic findings. Owing to heterogeneity in study design, sequencing methodology (16S rRNA vs. metagenomics), and reported outcomes, quantitative meta-analysis was not feasible. Instead, we undertook a narrative synthesis, with emphasis on consistent and divergent findings and on geographic patterns across cohorts from China, Europe, and the United States.

This review synthesizes emerging evidence on gut microbiota alterations in BC, with a particular emphasis on geographical variation across China, the USA, and Europe. To our knowledge, this is the first review to explicitly examine regional differences in gut microbiome cancer associations while incorporating species-level insights. Our findings highlight consistent signs of dysbiosis, identify potential candidate biomarkers, and point to opportunities for translational application, consistent with previous studies (35–37). At the same time, they underscore the methodological heterogeneity, modest evidence base, and predominance of cross-sectional designs that constrain definitive conclusions (19, 23, 34).

Overall, alpha diversity was reduced in BC patients in seven of the thirteen included studies (24, 25, 27, 28, 31, 33, 34), suggesting disrupted microbial homeostasis and a possible link to systemic inflammation (38, 39). However, two studies found increased alpha diversity (19, 26) and four reported no significant differences (23, 29, 30, 32). Beta diversity findings were similarly inconsistent; seven studies reported significant community-level shifts (19, 23–25, 28, 29, 33), whereas others observed no significant differences. These conflicting results likely reflect heterogeneity in study populations, particularly menopausal status, as well as methodological variability in sequencing approaches and the use of different diversity indices (40–42). Standardization of analytic pipelines will be essential to allow comparability across studies.

At the phylum level, four studies observed increased F/B ratios in BC patients (23, 26, 29, 31), consistent with pro-inflammatory states and altered energy harvesting (41, 43). In contrast, three studies reported no difference or reduced ratios (24, 25, 28), highlighting the influences of dietary and methodological influences (44, 45). These discrepancies highlight the limited utility of broad phylum-level metrics as reliable biomarkers. Such conflicting findings may reflect heterogeneity in host factors and study design, including dietary patterns (e.g., high-fiber vs. Western diets), sequencing approaches (16S rRNA vs. shotgun metagenomics), and menopausal status, which shapes the hormonal and metabolic milieu. Notably, compositional variability at the taxonomic level may converge functionally, through shared microbial outputs such as short-chain fatty acids or estrogen-modulating enzymes (10, 46). This functional redundancy suggests that integrative approaches combining compositional and metabolomic analyses are essential to elucidate the biological relevance of microbiome alterations in BC. More informative trends emerged at the genus level. Enrichment of Bacteroides, Blautia, Eggerthella and Parabacteroides in BC patients was observed across multiple studies (23, 24, 28, 29, 31, 34). These genera are linked to bile acid metabolism, pro-inflammatory signaling, and estrogen reactivation (47, 48). Eggerthella, in particular, is notable for β-glucuronidase activity, which may increase circulating bioactive estrogens and drive tumor progression (38, 49). Conversely, protective taxa, including Akkermansia, Collinsella, and Coprococcus were consistently depleted (19, 24, 25, 32–34). Of particular note, Akkermansia muciniphila was frequently reduced, consistent with its established role as a marker of mucosal health (50).

Species-level analysis, although limited to three metagenomic studies (23, 31, 32), yielded greater biomarker specificity. Faecalibacterium prausnitzii, a key butyrate producer with anti-inflammatory properties, was consistently reduced in BC patients (29, 33). By contrast, Eggerthella lenta and Parabacteroides distasonis showed inconsistent patterns of enrichment and depletion across cohorts (29, 31–33). These bidirectional results may reflect population-level dietary differences, strain-level functional variation, or technical inconsistencies (51, 52). Importantly, different taxonomic changes may converge on similar functional outcomes, such as reduced SCFA production or enhanced estrogen reactivation, suggesting that functional signatures may prove more reliable than taxonomy alone (53–55).

A major and novel contribution of this review is the comparative analysis of geographical variation. In the United States, enrichment of Acidaminococcus and Eggerthella was consistently reported (27–29), plausibly linked to high-fat, high-protein dietary patterns (45, 56). In Europe, Blautia enrichment was observed (31, 32), suggesting that fiber-driven microbial fermentation may influence breast (57, 58). In Chinese cohorts, enrichment of Prevotella and depletion of Akkermansia and Collinsella were common (19, 24, 25, 32, 33, 59, 60) reflecting carbohydrate-rich and fermented food dietary profiles (44, 45). Taken together, Asian cohorts showed Prevotella dominance and reduced SCFA-producing taxa, whereas Western cohorts were more likely to report enrichment of Blautia, Acidaminococcus, and Eggerthella. These patterns highlight how diet, ethnicity, and host factors interact with microbial ecology. However, translation into clinical application is premature. Regional differences complicate biomarker standardization but also create opportunities for precision nutrition and region-specific interventions (9, 61, 62). Contradictory findings, such as divergent F/B ratios or variable Collinsella levels, require careful appraisal. These discrepancies can be explained by methodological heterogeneity, including differences in DNA extraction, sequencing platform, and analytic pipelines. Clinical and demographic confounders, such as menopausal status, body mass index, antibiotic exposure, and treatment history, were often incompletely reported yet are known to shape microbiome composition. Importantly, taxonomic variability may still converge on functional similarity: reduced SCFA production, loss of barrier integrity, and enhanced estrogen metabolism are recurrent themes. Future work must therefore integrate metagenomics, metabolomics, and metatranscriptomics to link compositional changes with mechanistic outputs (8).

The potential of the gut microbiome as a predictive biomarker in BC should be viewed as preliminary. Current evidence is largely cross-sectional and insufficient to establish causality. Nevertheless, recurring signals, such as depletion of Faecalibacterium prausnitzii and Akkermansia muciniphila, provide biologically plausible candidate biomarkers that merit validation (42, 50, 63). Integration with established predictors, including circulating estrogen, inflammatory markers, hormone receptor status, and genomic risk scores, could yield multi-modal models with greater predictive power (64, 65). In practice, stool-based microbiome profiling could emerge as a low-cost, non-invasive adjunct, but clinical application will require reproducible assays, validated thresholds, and demonstration of incremental benefits (9, 49). Microbiota-based interventions represent a promising but as yet untested avenue in BC (63, 66). Evidence from other cancers indicates that dietary fiber, probiotics, and fecal microbiota transplantation can modulate therapeutic response (62, 66, 67). In breast cancer, dietary modification, particularly fiber enrichment or polyphenol supplementation, may support protective taxa such as Faecalibacterium and Akkermansia. Probiotic and prebiotic interventions targeting estrogen metabolism or SCFA production are theoretically attractive but require robust testing in controlled trials (50, 63, 66).

This review has several strengths, including its structured literature search, inclusion of species-level analyses, and integration of geographical perspectives, which have been largely overlooked in prior work. However, important limitations must be acknowledged. Only 13 studies met eligibility criteria, reflecting the early stage of this field. Most were small, cross-sectional studies relying on 16S rRNA sequencing, which restricts taxonomic resolution. Only three employed metagenomic approaches, which are needed for functional insight. Menopausal status, body mass index, and antibiotic use were inconsistently reported, limiting comparability. Restriction to English-language publications may have introduced selection bias. A formal risk-of-bias assessment was not conducted, consistent with the Mini Review format, but methodological variability was qualitatively addressed.

Future research should therefore prioritize prospective designs to establish temporal and causal relationships between dysbiosis and breast cancer (68). Microbiome signatures should be integrated with established biomarkers in multivariable models to test whether they improve prediction. Region-specific interventions should be trialed, recognizing that microbiome–diet interactions are culturally and geographically contingent (13). Functional profiling must be incorporated to reconcile taxonomic heterogeneity and clarify biological plausibility. Harmonization of methods for sampling, sequencing, and analysis will be critical to reproducibility (69). Finally, international collaborations are needed to validate microbial predictors across diverse populations, including underrepresented regions such as Africa and South America, ensuring equitable global translation (61, 67, 70).

In conclusion, while the gut microbiome cannot yet be regarded as an established predictive biomarker for BC, the trajectory of current research suggests considerable promise. Consistent signals at genus and species levels, functional links to estrogen metabolism and inflammation, and region-specific variation provide a biologically credible foundation for further study. Translation into clinical practice will depend on large-scale, longitudinal, standardized studies capable of establishing causality and reproducibility. If achieved, microbiome-informed approaches may ultimately contribute to precision oncology by enhancing risk stratification, guiding dietary counselling, and supporting the development of microbiome-targeted interventions.