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MINI REVIEW article

Front. Oncol., 17 June 2025

Sec. Breast Cancer

Volume 15 - 2025 | https://doi.org/10.3389/fonc.2025.1617410

Effects of gut microbiota in breast cancer

Leping KangLeping Kang1Haiyang ChenHaiyang Chen2Chengjun HeChengjun He2Junchuan Li*Junchuan Li3*
  • 1Department of Thyroid and Breast Surgery, Central Hospital of Ziyang, Sichuan, Ziyang, China
  • 2Department of hepatobiliary and pancreatic Surgery, Central Hospital of Ziyang, Sichuan, Ziyang, China
  • 3Department of General Surgery, Yanjiang District people’s Hospital of Ziyang, Sichuan, Ziyang, China

Breast cancer (BC) stands as the predominant form of cancer affecting women globally, with its etiology rooted in a complex interplay of factors. Emerging research underscores the significant impact of microbiota on the development of BC. Evidence points to a correlation between BC and microbial imbalance, not only within the intestinal milieu but also in breast tissue itself. Alterations in the diversity and functionality of bacterial populations in these areas are implicated in the disease’s pathogenesis.The intestinal microbiota exerts a pivotal influence on the metabolism of steroid hormones, including estrogens, which are recognized as critical elements in the risk profile for BC, particularly among women who have reached menopause. These hormones can drive the onset and advancement of BC via multiple mechanisms. Concurrently, a body of research highlights the contributory roles of immune system elements, inflammatory processes, dietary patterns, and the use of probiotics in the context of BC. Understanding this intricate interplay holds promise for developing innovative therapeutic approaches

Introduce

Breast cancer (BC), representing 32% of newly diagnosed cancer cases, stands as one of the most prevalent malignancies among women globally. Despite substantial advancements in diagnostic and therapeutic approaches, the five-year survival rate for BC patients averages 89.2%, with tumor stage being a critical determinant of disease progression (1). Specifically, the survival rate exceeds 98% for stage I tumors but drops significantly to 24% for stage III tumors. While factors such as diet, alcohol consumption, and radiation exposure have been linked to an elevated risk of BC, emerging research highlights the potential role of the human microbiome in influencing this disease (2, 3). Both the gut microbiota and the local microbiota within the mammary gland have been proposed to impact BC progression. This review aims to elucidate the mechanisms through which the gut microbiota may contribute to cancer development, with a particular focus on BC, and to summarize clinical trials investigating alterations or modifications in the microbiota of women diagnosed with BC (46).

General situation

For a long time, the mammary gland was assumed to be a sterile environment. However, current research has revealed the presence of a distinct microbiota within it (7). Structurally, the breast mainly consists of adipose tissue, complemented by an extensive network of blood vessels and lymphatic drainage. This unique physiological makeup creates a favorable ecological niche for the growth of bacteria, particularly Proteobacteria and Firmicutes (8). Through culture - based experiments, the existence of viable bacteria in the mammary tissue has been conclusively demonstrated. Among the identified species are Bacillus sp., Enterobacteriaceae sp., and Staphylococcus sp (7). In a study involving Asian BC patients, researchers discovered an enrichment of Propionicimonas, Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae, and Methylobacteriaceae within tumor tissues (9). In general, BC patients often exhibit a reduction in microbial diversity, accompanied by significant changes in the composition of their microbiota (10). In a separate clinical trial, Luu et al. observed substantial differences in the absolute counts of total bacteria, Firmicutes, Faecalibacterium prausnitzii, and Blautia in fecal samples. Intriguingly, these findings were closely correlated with the body mass index (BMI) of women with early - stage BC. Specifically, overweight and obese patients were found to have a lower bacterial count (11).Consistent with these findings, other research groups have reported that BC patients typically have a lower relative abundance of Firmicutes and Bacteroidetes in their feces, while simultaneously showing an elevated relative abundance of Verrucomicrobia and Proteobacteria (12). Frugé et al., in their investigation of early - stage BC patients, found that body composition was inversely associated with the abundance of Akkermansia muciniphila. Conversely, it was positively correlated with interleukin - 6 levels. Additionally, they reported that the relative abundance of Akkermansia muciniphila was linked to key health - related outcome parameters and was associated with beneficial dietary modifications (13).In a comparative study of breast tissue samples from BC patients and healthy controls, Propionibacterium and Staphylococcus were found to be depleted in tumor tissues. This depletion was negatively associated with oncogenic immune features. On the other hand, Streptococcus and Propionibacterium were positively correlated with genes related to T - cell activation (14). Costantini’s research identified Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes as being associated with breast tumors, with Ralstonia being the most dominant genus among them (15). Meng, using a Chinese patient cohort, observed an increased representation of the genus Propionicimonas, as well as the families Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae, and Methylobacteriaceae in malignant breast tumor tissues. Nevertheless, it is essential to acknowledge that these results may be influenced by the ethnic - specific characteristics inherent to the studied population (16). Differences in the urine microbiota of BC patients have also been identified. These differences are characterized by an increased presence of gram - positive organisms, including Corynebacterium, Staphylococcus, Actinomyces, and Propionibacteriaceae, and a concurrent decrease in the abundance of Lactobacillus. Nejman et al. further demonstrated that breast tumor samples had a higher bacterial load and species richness compared to breast samples obtained from healthy subjects within the studied population (17). Notably, in women with the HER2+ subtype of BC, which is known for its aggressive growth and rapid spread, there was a decrease in fecal α - diversity and Firmicutes abundance, while the abundance of Bacteroidetes was found to be elevated (18).

Estrogen and microbiota

Exposure to hormones ranks as one of the most significant factors linked to the development of BC, especially among postmenopausal women. In this context, the concept of the estrobolome is of particular significance. The estrobolome encompasses a set of microbial genes whose products are actively involved in the complex process of estrogen metabolism (19). Numerous studies have convincingly demonstrated that a specific subset of microorganisms residing within the gastrointestinal tract exerts a notable influence on estrogen metabolism. This influence extends to regulating the delicate balance between circulating estrogen levels in the bloodstream and those excreted from the body (20). More specifically, free estrogens are predominantly generated through a deconjugation process that occurs within the gut environment. This process is facilitated by the enzyme bacterial β - glucuronidase, which is particularly active within microbial communities such as those belonging to the Clostridia and Ruminococcaceae families, or the Escherichia/Shigella genus (21, 22). The journey of estrogen metabolism commences in the liver. Here, estrogens undergo conjugation reactions, after which they are excreted into the gastrointestinal lumen as part of the bile. Once in the gut, the conjugated estrogens encounter bacterial β - glucuronidase, which breaks them down through de - conjugation. The resulting free estrogens are then re - absorbed into the bloodstream through the enterohepatic circulation. This process allows the free estrogens to reach various organs throughout the body, with the breast being one of the key destinations (2325). In addition to its role in estrogen metabolism, β - glucuronidase may also play a major part in the deconjugation of endocrine - disrupting chemicals. These chemicals can disrupt the normal composition and function of the gut microbiota. Moreover, they can also alter the metabolites produced by these microorganisms, potentially leading to an increase in inflammation within the body (26). Therefore, any perturbations or imbalances in the microbiota - estrobolome axis can lead to an elevation in the levels of circulating estrogens and their metabolites. This increase in estrogenic activity is a well - recognized risk factor for the development of BC, as it can potentially stimulate the growth and proliferation of BC cells.

Available literature indicates that postmenopausal women with BC exhibit increased levels of Clostridiaceae in their fecal microbiota (27). However, a study by Angioletta reported no significant disparities in microbial profiles between patients experiencing disease relapse during aromatase inhibitor therapy and relapse-free control subjects. Instead, this investigation highlighted that the Clostridia class and Clostridiales order represented the most abundant taxonomic groups within the case cohort. Notably, the Veillonella family, which was enriched in BC cases, possesses the capacity to synthesize β-glucuronidase—an enzyme implicated in augmenting free estrogen levels through deconjugation reactions (28).

A diverse array of bacterial taxa are capable of synthesizing β-glucuronidase, including genera such as Alistipes, Bacteroides, Bifidobacterium, Collinsella, Edwardsiella, and Faecalibacterium, alongside specific species within the Lactobacillus and Roseburia clades (29, 30). Given the pivotal role of the gut microbiota in modulating intratumoral inflammatory and immune microenvironments, variations in microbial composition—including shifts between eubiosis and dysbiosis—are hypothesized to influence the clinical response to hormone therapy (31). Additionally, although direct evidence remains lacking, a mechanistic link is proposed whereby microbiota-mediated elevations in estrogen bioavailability or enzymatic degradation of orally administered hormonal agents may alter drug pharmacokinetics, thereby impacting therapeutic efficacy.Accumulating evidence indicates that certain gut-resident bacterial species encode enzymes capable of modulating the enterohepatic circulation of estrogen metabolites, facilitating conversions of estrogens to androgens or biosynthesis of estrogen-mimetic molecules (32). Preclinical studies in murine models have shown that prolonged estrogen supplementation disrupts gut microbiota composition—specifically leading to a decrease in Akkermansia muciniphila abundance—and alters β-glucuronidase activity, collectively indicating a bidirectional interaction where estrogen homeostasis influences microbiome dynamics (33).

Direct action

Live bacteria have been identified within tumor cells and tumor-associated immune cells (4, 17), suggesting that cancerous and host cells may serve as carriers to facilitate the spread of microorganisms to tumors or adjacent normal mammary tissues (34). In the context of BC, Parida et al. demonstrated that gut colonization with enterotoxigenic Bacteroides fragilis (ETBF), which secretes B. fragilis toxin (BFT), induces epithelial hyperplasia in the mammary gland. Furthermore, in vitro treatment of BC MCF7 cells with BFT prior to injection in mice significantly accelerated tumor growth and metastasis through the β-catenin and Notch1 signaling pathways (19). Gut-resident bacteria may translocate to the mammary gland via breaches in the intestinal epithelium, a common occurrence during dysbiosis, and travel through the bloodstream or lymphatic system. Alternatively, intestinal dendritic cells, which can penetrate tight junctions between epithelial cells to uptake bacteria, may transport these microorganisms to distant sites, including mammary tissue, via the vascular system (35). It has been hypothesized that alterations in bacterial abundance or composition within tumors may result from the disease itself, as the leaky vasculature of the tumor microenvironment could facilitate bacterial recruitment (36). Urbaniak et al. investigated the ability of bacterial isolates from adjacent normal tissue of BC patients to induce DNA double-stranded breaks (37). Additionally, nisin, a bacteriocin produced by the Gram-positive Lactococcus lactis, has demonstrated potent cytotoxic effects on breast tumor cells by disrupting calcium ion influx and inducing cell cycle arrest (38). Another example is Bacteroides fragilis, a gut bacterium also found in the mammary gland, whose toxin can promote epithelial hyperplasia, tumor growth, and metastasis via the β-catenin–Notch1 axis (19). Furthermore, Fusobacterium nucleatum, previously linked to colorectal cancer, has been implicated in BC progression. This bacterium activates the TLR4/NF-κB pathway in cancer cells (3942) and, through its Fap2 lectin protein, binds to Gal-GalNAc, a sugar highly expressed on breast tumor cells. This interaction accelerates tumor growth and metastasis (43, 44).

Immune system

Initially, BC was thought to be a non-immunogenic tumor. However, recent studies have revealed that the expression of immune-related genes and the presence of immune infiltrates in primary tumors are associated with improved clinical outcomes (45). The gut microbiota influences the immune system of BC patients by regulating the proliferation and differentiation of regulatory T cells, inducing the expression of secretory immunoglobulin A (sIgA), and modulating neutrophil production. Reduced microbiome diversity has been linked to poorer survival rates in BC patients, suggesting a critical role for microbial balance in disease progression. Researchers have proposed that gut microbiota dysbiosis can disrupt the host immune system, with IgA protein serving as a potential link between BC-related inflammation and gut microbiota (46). A 2018 case-control study found that IgA+ patients exhibited significantly lower microbiota abundance and α-diversity compared to IgA- patients, indicating that gut microbiota may influence BC development by altering immune pathways (47). These immune alterations are often accompanied by changes in immune cell populations, including decreased lymphocyte levels and increased neutrophil counts (48). Neutrophils, in particular, have been shown to be influenced by gut microbiota in the context of BC. For example, in the C3-1-TAg mammary cancer mouse model, infection with Helicobacter hepaticus (a gut-resident bacterium) promoted BC progression, correlating with increased neutrophil recruitment and infiltration at the tumor site (49). Additionally, M2-like macrophages, the predominant immune subset in the breast tumor microenvironment, are associated with reduced survival in hormone receptor-positive (HR+) BC. These macrophages infiltrate both breast tumors and adjacent normal mammary tissues during early and advanced stages of tumor progression (50, 51).

Furthermore, specific gut bacteria have been shown to modulate the immune response in a way that either promotes or suppresses tumor development, largely through the regulation of stimulator of interferon genes (STING) agonists. For instance, the presence of Akkermansia muciniphila, a gut bacterium that produces cyclic di-AMP (cdAMP), has been observed to activate the STING pathway, leading to the induction of the type I interferon (IFN-I) pathway. This IFN-I production reprograms macrophages into an anti-tumor phenotype and enhances the crosstalk between natural killer (NK) cells and dendritic cells (DCs), thereby fostering a robust anti-tumor immune response (52). Zubaida et al. explored the anti-cancer potential of heat-killed cells (HKC) and cytoplasmic fractions (CF) of Enterococcus faecalis and Staphylococcus hominis in the MCF-7 BC cell line. Both bacterial forms significantly reduced MCF-7 cell proliferation, induced apoptosis, and caused cell cycle arrest in a concentration- and time-dependent manner (53). The presence of these bacteria was also positively correlated with the production of trimethylamine N-oxide (TMAO), a metabolite known to activate CD8+ T cell-mediated anti-tumor immunity and promote M1 macrophage polarization. This further supports the concept of a metabolically active, tissue-resident microbiota playing a role in cancer immunity (54). In a recent study involving triple-negative BC patients, a high abundance of Clostridiales in tumor tissue was associated with an activated immune microenvironment (55). Additionally, Sphingomonas, a bacterium detected in healthy mammary tissue, has been shown to activate invariant natural killer T (iNKT) cells (56), which are critical mediators of cancer immunosurveillance and the control of BC metastases (54). Notably, higher levels of Sphingomonas in healthy mammary tissue compared to tumor tissue have been linked to increased expression of Toll-like receptors (TLR2, TLR5, and TLR9) and antimicrobial effectors such as IL-12A, bactericidal/permeability-increasing protein (BPI), and myeloperoxidase (MPO). This suggests a potential protective role of Sphingomonas in cancer by enhancing immunosurveillance (57).

Emerging evidence suggests that shifts in the abundance of specific gut microbiota can modulate immune responses by increasing the production of regulatory T cells (Tregs) or reducing the differentiation of pathogenic T cells, potentially mitigating inflammatory diseases (58). Collectively, these findings highlight the role of microbial DNA and bacterial metabolites in shaping the local immune microenvironment within the breast. This implies that commensal bacteria may directly influence tumor progression through their metabolic activity, which can alter immune cell behavior and regulate inflammatory processes.

Inflammation and microbiota

Inflammation is a hallmark of carcinogenesis, irrespective of the underlying cause, and is considered a primary oncogenic mechanism driven by the microbiota (59). Microbial virulence factors can trigger chronic inflammation in host tissues, promoting excessive cell proliferation. When this proliferation becomes dysregulated and is coupled with impaired apoptosis, it can initiate the carcinogenic process (60, 61).

Certain harmful microbes in the human gut, like Escherichia coli and Serrella, are able to heighten chronic inflammation and autoimmune reactions. They do this either by generating endotoxins or by stimulating the differentiation and function of Th17 cells (62). Gut bacteria can contribute to BC development through chronic inflammation, which is closely tied to tumorigenesis. These bacteria can cause an upregulation of Toll - like receptors (TLR) and activate NF - κB. NF - κB is vital for inflammation regulation and has a connection with cancer. Once activated, it leads to the release of cytokines such as IL - 6, IL - 12, IL - 17 and IL - 18. This, in turn, triggers ongoing inflammation within the tumor microenvironment (6365). Inflammation triggered by pathogens isn’t restricted to the infection site. For instance, C57BL/6 ApcMin/+ mice, which have a genetic tendency to develop breast carcinomas, won’t develop breast tumors if they’re raised in a specific pathogen - free environment (66). But when Helicobacter hepaticus is administered to them via the stomach, they develop mammary carcinomas because of the activation of the innate immune response through inflammation (67, 68). Conversely, beneficial gut microbes such as bifidobacterium and lactic acid bacteria can boost the production of short - chain fatty acids (SCFAs). The increased SCFAs can promote the differentiation and function of Tregs. As a result, chronic inflammation and autoimmune responses are inhibited (69).

As highlighted by Angioletta, estrogens exert anti-inflammatory effects by directly modulating CD16 expression, thereby reducing pro-inflammatory IL-6 (70). Concurrently, these sex hormones are shown to influence the homeostasis of NK cell populations, underscoring their dual role in immune regulation and inflammation control.Available evidence from these investigations indicates that specific antimicrobial agents may diminish inflammatory mediators—at least in the short term—by enhancing the excretion of conjugated estrogens, potentially lowering the risk of BC through this mechanistic pathway (21). However, the long-term effects of antibiotic use on estrogen elimination dynamics and associated cancer risk remain unexplored, representing a critical knowledge gap in this field.

Thus, it can be concluded that chronic inflammation plays a critical role in both the initiation and progression of BC. The persistent presence of inflammatory cytokines and the recruitment of immune cells, such as Tregs, contribute to a suppressed immune response, facilitating tumor immune escape and promoting cancer progression.

Diet and microbiota

Dietary changes are well-documented to influence the composition and function of the gut microbiome (62). Approximately 35% of all cancers, including 50% of breast carcinomas, are linked to dietary factors (63). In diet-associated BC, microbial-mediated mechanisms are thought to play a role in modulating carcinogenesis and tumor aggressiveness (64). Diets rich in mono- and polyunsaturated fatty acids, gut microbiota-accessible carbohydrates, fruits, vegetables, and legumes are associated with improved overall health and may offer protective effects against cancer risk and mortality, including BC (65, 66). Hypercholesterolemia has been identified as a risk factor for estrogen receptor (ER)-positive BC (67). The cholesterol metabolite 27-hydroxycholesterol (27HC) exhibits estrogenic activity and has been shown to promote breast tumor growth in xenograft mouse models by binding to ERs on mammary gland epithelial cells and stimulating proliferation (68). However, its role in humans remains to be fully elucidated (69).The mechanistic link between alcohol consumption and BC may involve several pathways: 1) alcohol may enhance ER signaling in breast tumors or elevate endogenous steroid hormone levels (71); 2) ethanol can stimulate the transcriptional activity of ER-α in human BC cell lines in a dose-dependent manner while downregulating BRCA1, a gene that inhibits ER-α transcriptional activity (72); and 3) in healthy postmenopausal women not on hormone replacement therapy (HRT), daily alcohol consumption of 15–30 g was associated with a 7.5% and 10.7% increase in serum estrone sulfate levels, respectively, compared to non-drinkers (71).

Probiotics and prebiotics on microbiota

Probiotics are live microorganisms that help maintain a healthy gut microbiota and restore beneficial microbial balance (73). Research by Imani Fooladi demonstrated that treatment with Lactobacillus acidophilus significantly extended the survival time of BC mice compared to a control group (74). Members of the Lactobacillus and Bifidobacterium genera exhibit therapeutic potential in shaping the tumor microenvironment through dual mechanisms: regulating cytokine profiles and augmenting the activity of NK cells alongside cytotoxic T lymphocytes (CTLs) (75). One of the key features of probiotics is their ability to produce beneficial compounds, such as antibiotics, anticarcinogens, and other substances with positive effects on overall health and pharmaceutical properties (76). Epidemiological studies have linked the consumption of fermented dairy products to a reduced risk of BC, potentially due to changes in the gut microbiota that alter the enterohepatic cycling of estrogenic compounds. Marschalek et al. found that oral probiotic formulations could improve the vaginal microbiota in postmenopausal BC patients undergoing chemotherapy, highlighting a potential therapeutic application of probiotics in BC management (77). Further supporting this, Imani Fooladi et al. showed that daily oral administration of L. acidophilus two weeks before BC tumor transplantation and continued for 30 days significantly increased overall survival, suggesting that L. acidophilus may enhance immune responses and boost anti-tumor activity (74). Clinical trials and retrospective analysis have also demonstrated that probiotics can improve quality of life, reduce therapy-related toxicities, and mitigate complications in cancer patients (75). For example, in Japanese women, regular consumption of Lactobacillus casei Shirota and soy isoflavones from adolescence was associated with a reduced risk of BC, indicating potential chemopreventive effects (78). Chung introduced a innovative strategy for bacterial-mediated delivery of therapeutic proteins to colorectal cancer lesions, leveraging metabolic pathway rewiring to overcome promoter-associated limitations and enhance treatment precision and efficacy (79), but the translational potential of this approach to BC remains unestablished and warrants further preclinical validation.Concurrently, Prasoon highlighted the emerging role of artificial intelligence (AI)-driven synthetic biology methodologies in optimizing the therapeutic and nutritional attributes of probiotics (80). This technological paradigm shift is poised to revolutionize microbial engineering by enabling precise modulation of probiotic functions, which may have far-reaching implications for cancer therapeutics and host-microbiota interactions.

Prebiotics are non-digestible dietary compounds that promote the growth or activity of beneficial gut microorganisms (81)[. Dietary fiber, a common prebiotic, can modulate the gut microbiota and influence estradiol metabolism by affecting specific enzyme activities, such as β-glucuronidase, particularly in postmenopausal BC patients (82). Zengul et al. investigated the interplay between dietary fiber and gut microbiota, focusing on their role in enhancing β-glucuronidase activity and increasing circulating estrogen levels in postmenopausal BC patients (83).

When the gut microbiota is in a state of equilibrium, known as eubiosis, it can serve as a protective factor against cancer. This is achieved through the fermentation of dietary fiber, which helps maintain the integrity of the intestinal mucosa and supports the immune system, potentially triggering anti-tumor immune responses. Preclinical studies have suggested that probiotics may act as moderators to prevent or control BC progression by enhancing the host’s immune system. However, further research through clinical trials and prospective studies is necessary to confirm the efficacy of probiotics in the clinical management of BC.

Antibiotics and microbiota

The use of antibiotics in cancer patients is a highly debated topic. Antibiotics are often prescribed in conjunction with chemotherapy and cancer surgeries. In certain types of cancer, like BC and melanoma, it has been noted that antibiotics can speed up disease progression (84). A case - control study involving 2266 North American women with BC and 7953 healthy controls revealed that women with a history of long - term antibiotic treatment had an increased risk of developing BC (85). A recent meta - analysis indicated that the type of antibiotic might be linked to BC risk. Specifically, the risk was slightly higher when patients were treated with penicillin, tetracycline, and nitrofuran, and there was a marginal increase with the use of nitroimidazole and metronidazole (86). In a study using BC mouse models, the administration of antibiotics led to a decrease in fecal butyrate levels and an increase in tumor growth (87). However, more large - scale prospective studies are needed to better clarify the role of antibiotics as a biomarker and in cancer treatment (88).

Fecal microbiota transplantation and AI

In an investigation by Xu, ovarian cancer cell xenografts in mice with intestinal microbiota dysbiosis exhibited enhanced tumor growth compared to control groups (89). This dysbiotic state activated macrophages, leading to elevated circulating levels of interleukin IL-6 and TNF-α, which in turn promoted epithelial-mesenchymal transition (EMT) in ovarian cancer cells.A separate study utilizing antibiotic-induced microbiota-depleted mice to model endometriosis progression revealed that microbial depletion attenuated endometriotic lesion growth (90). Reciprocally, oral gavage of fecal microbiota from endometriosis-bearing mice restored lesion expansion in MD recipients, indicating a causal role for gut microbial composition in disease progression. While FMT has emerged as a promising approach for treating various cancers—including colorectal, hepatic, and pancreatic malignancies, melanoma, Clostridioides difficile infection, and radiation enteritis—its application in BC remains underinvestigated (9193). Although the precise molecular and cellular mechanisms underpinning FMT’s effects remain unclear, proposed pathways involve direct interactions between donor microbiota, host intestinal epithelium, and immune system (94). These interactions are hypothesized to modulate intestinal mucosal barrier integrity, inflammatory signaling, and anti-tumor immune responses, highlighting the need for targeted studies to elucidate FMT’s role in BC management.

Historically, investigations into the gut microbiome have predominantly relied on traditional techniques such as 16S rRNA sequencing. However, this approach is constrained by its limited taxonomic resolution and inability to characterize the functional activities of microbial communities, thereby restricting mechanistic insights into host-microbiota interactions. AI has increasingly been integrated into medical research and applications. In the context of gut microbiota studies, a key challenge in leveraging AI lies in integrating multi-omics datasets to characterize the intricate interactions between the microbiome and host systems—encompassing metabolic, immune, and neural pathways. To tackle this complexity, researchers are progressively adopting integrated multi-omics frameworks that combine genomic, transcriptomic, proteomic, and metabolomic data, enabling comprehensive modeling of host-microbiota interactions at multiple biological scales (95). AI-driven models have demonstrated utility in discriminating between healthy and dysbiotic microbiome profiles, enabling the identification of potential biomarkers for diseases such as inflammatory bowel disease, obesity, and colorectal cancer (96). Despite these advancements, Critical challenges include the need for large, rigorously annotated training datasets and the risk of model overfitting to cohort-specific biases, which compromise the generalizability of such approaches for common tumors—including BC (97).

Conclusions

Research into the possible interactions between the gut microbiome and BC encompasses the entire translational research spectrum. This type of study calls for cooperation among various professionals. These include basic scientists like immunologists, who study the immune system; cell biologists, who focus on the structure and function of cells; and microbiologists, who deal with microorganisms. Clinicians such as oncologists, who treat cancer patients, and endocrinologists, who specialize in hormone - related disorders, are also crucial. Additionally, animal researchers, who conduct experiments on animals to understand biological processes, epidemiologists, who study the patterns and causes of diseases in populations, biostatisticians, who analyze biological data using statistical methods, and bioinformaticians, who manage and analyze biological data using computational tools, all need to work together.

Author contributions

HC: Writing – review & editing, Conceptualization. CH: Writing – review & editing, Investigation. JL: Project administration, Writing – review & editing. LK: Writing – review & editing, Supervision, Conceptualization, Funding acquisition.

Funding

The author(s) declare that no financial support was received for the research and/or publication of this article.

Acknowledgments

The authors highly appreciate all the members who were involved in the present study.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

1. Siegel RL, Giaquinto AN, and Jemal A. Cancer statistics, 2024. CA Cancer J Clin. (2024) 74:12–49. doi: 10.3322/caac.21820

PubMed Abstract | Crossref Full Text | Google Scholar

2. Fernández MF, Reina-Pérez I, Astorga JM, Rodríguez-Carrillo A, Plaza-Díaz J, and Fontana L. Breast cancer and its relationship with the microbiota. Int J Environ Res Public Health. (2018) 15:1747. doi: 10.3390/ijerph15081747

PubMed Abstract | Crossref Full Text | Google Scholar

3. van Gemert WA, Lanting CI, Goldbohm RA, van den Brandt PA, Grooters HG, Kampman E, et al. The proportion of postmenopausal breast cancer cases in the Netherlands attributable to lifestyle-related risk factors. Breast Cancer Res Treat. (2015) 152:155–62. doi: 10.1007/s10549-015-3447-7

PubMed Abstract | Crossref Full Text | Google Scholar

4. Fu A, Yao B, Dong T, Chen Y, Yao J, Liu Y, et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer. Cell. (2022) 185:1356–1372.e26. doi: 10.1016/j.cell.2022.02.027

PubMed Abstract | Crossref Full Text | Google Scholar

5. Bernardo G, Le Noci V, Ottaviano E, De Cecco L, Camisaschi C, Guglielmetti S, et al. Reduction of Staphylococcus epidermidis in the mammary tumor microbiota induces antitumor immunity and decreases breast cancer aggressiveness. Cancer Lett. (2023) 555:216041. doi: 10.1016/j.canlet.2022.216041

PubMed Abstract | Crossref Full Text | Google Scholar

6. Ruo SW, Alkayyali T, Win M, Tara A, Joseph C, Kannan A, et al. Role of gut microbiota dysbiosis in breast cancer and novel approaches in prevention, diagnosis, and treatment. Cureus. (2021) 13:e17472. doi: 10.7759/cureus.17472

PubMed Abstract | Crossref Full Text | Google Scholar

7. Urbaniak C, Cummins J, Brackstone M, Macklaim JM, Gloor GB, Baban CK, et al. Microbiota of human breast tissue. Appl Environ Microbiol. (2014) 80:3007–14. doi: 10.1128/AEM.00242-14

PubMed Abstract | Crossref Full Text | Google Scholar

8. O’Connor H, MacSharry J, Bueso YF, Lindsay S, Kavanagh EL, Tangney M, et al. Resident bacteria in breast cancer tissue: pathogenic agents or harmless commensals. Discov Med. (2018) 26:93–102. doi: 10.1101/553602

Crossref Full Text | Google Scholar

9. Meng Z, Ye Z, Zhu P, Zhu J, Fang S, Qiu T, et al. New developments and opportunities of microbiota in treating breast cancers. Front Microbiol. (2022) 13:818793. doi: 10.3389/fmicb.2022.818793

PubMed Abstract | Crossref Full Text | Google Scholar

10. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. (2004) 101:15718–23. doi: 10.1073/pnas.0407076101

PubMed Abstract | Crossref Full Text | Google Scholar

11. Luu TH, Michel C, Bard JM, Dravet F, Nazih H, and Bobin-Dubigeon C. Intestinal proportion of blautia sp. is associated with clinical stage and histoprognostic grade in patients with early-stage breast cancer. Nutr Cancer. (2017) 69:267–75. doi: 10.1080/01635581.2017.1263750

PubMed Abstract | Crossref Full Text | Google Scholar

12. Ma J, Sun L, Liu Y, Ren H, Shen Y, Bi F, et al. Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer. BMC Microbiol. (2020) 20:82. doi: 10.1186/s12866-020-01739-1

PubMed Abstract | Crossref Full Text | Google Scholar

13. Frugé AD, van der Pol W, Rogers LQ, Morrow CD, Tsuruta Y, and Demark-Wahnefried W. Fecal akkermansia muciniphila is associated with body composition and microbiota diversity in overweight and obese women with breast cancer participating in a presurgical weight loss trial. J Acad Nutr Diet. (2020) 120:650–9. doi: 10.1016/j.jand.2018.08.164

PubMed Abstract | Crossref Full Text | Google Scholar

14. Tzeng A, Sangwan N, Jia M, Liu CC, Keslar KS, Downs-Kelly E, et al. Human breast microbiome correlates with prognostic features and immunological signatures in breast cancer. Genome Med. (2021) 13:60. doi: 10.1186/s13073-021-00874-2

PubMed Abstract | Crossref Full Text | Google Scholar

15. Costantini L, Magno S, Albanese D, Donati C, Molinari R, Filippone A, et al. Characterization of human breast tissue microbiota from core needle biopsies through the analysis of multi hypervariable 16S-rRNA gene regions. Sci Rep. (2018) 8:16893. doi: 10.1038/s41598-018-35329-z

PubMed Abstract | Crossref Full Text | Google Scholar

16. Meng S, Chen B, Yang J, Wang J, Zhu D, Meng Q, et al. Study of microbiomes in aseptically collected samples of human breast tissue using needle biopsy and the potential role of in situ tissue microbiomes for promoting Malignancy. Front Oncol. (2018) 8:318. doi: 10.3389/fonc.2018.00318

PubMed Abstract | Crossref Full Text | Google Scholar

17. Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science. (2020) 368:973–80. doi: 10.1126/science.aay9189

PubMed Abstract | Crossref Full Text | Google Scholar

18. Wu AH, Tseng C, Vigen C, Yu Y, Cozen W, Garcia AA, et al. Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study. Breast Cancer Res Treat. (2020) 182:451–63. doi: 10.1007/s10549-020-05702-6

PubMed Abstract | Crossref Full Text | Google Scholar

19. Parida S, Wu S, Siddharth S, Wang G, Muniraj N, Nagalingam A, et al. A procarcinogenic colon microbe promotes breast tumorigenesis and metastatic progression and concomitantly activates notch and β-catenin axes. Cancer Discov. (2021) 11:1138–57. doi: 10.1158/2159-8290.CD-20-0537

PubMed Abstract | Crossref Full Text | Google Scholar

20. Flores R, Shi J, Fuhrman B, Xu X, Veenstra TD, Gail MH, et al. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. J Transl Med. (2012) 10:253. doi: 10.1186/1479-5876-10-253

PubMed Abstract | Crossref Full Text | Google Scholar

21. Kwa M, Plottel CS, Blaser MJ, and Adams S. The intestinal microbiome and estrogen receptor-positive female breast cancer. J Natl Cancer Inst. (2016) 108:djw029. doi: 10.1093/jnci/djw02

PubMed Abstract | Crossref Full Text | Google Scholar

22. Shapira I, Sultan K, Lee A, and Taioli E. Evolving concepts: how diet and the intestinal microbiome act as modulators of breast Malignancy. ISRN Oncol. (2013) 2013:693920. doi: 10.1155/2013/693920

PubMed Abstract | Crossref Full Text | Google Scholar

23. Rea D, Coppola G, Palma G, Barbieri A, Luciano A, Del Prete P, et al. Microbiota effects on cancer: from risks to therapies. Oncotarget. (2018) 9:17915–27. doi: 10.18632/oncotarget.24681

PubMed Abstract | Crossref Full Text | Google Scholar

24. Li X, Yang J, Peng L, Sahin AA, Huo L, Ward KC, et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. (2017) 161:279–87. doi: 10.1007/s10549-016-4059-6

PubMed Abstract | Crossref Full Text | Google Scholar

25. Laborda-Illanes A, Sanchez-Alcoholado L, Dominguez-Recio ME, Jimenez-Rodriguez B, Lavado R, Comino-Méndez I, et al. Breast and gut microbiota action mechanisms in breast cancer pathogenesis and treatment. Cancers (Basel). (2020) 12:2465. doi: 10.3390/cancers12092465

PubMed Abstract | Crossref Full Text | Google Scholar

26. DeLuca JA, Allred KF, Menon R, Riordan R, Weeks BR, Jayaraman A, et al. Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis. Exp Biol Med (Maywood). (2018) 243:864–75. doi: 10.1177/1535370218782139

PubMed Abstract | Crossref Full Text | Google Scholar

27. Goedert JJ, Jones G, Hua X, Xu X, Yu G, Flores R, et al. Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study. J Natl Cancer Inst. (2015) 107:djv147. doi: 10.1093/jnci/djv147

PubMed Abstract | Crossref Full Text | Google Scholar

28. Lasagna A, De Amici M, Rossi C, Zuccaro V, Corbella M, Petazzoni G, et al. The bio-diversity and the role of gut microbiota in postmenopausal women with luminal breast cancer treated with aromatase inhibitors: an observational cohort study. Pathogens. (2022) 11:1421. doi: 10.3390/pathogens11121421

PubMed Abstract | Crossref Full Text | Google Scholar

29. Edwinson AL, Yang L, Peters S, Hanning N, Jeraldo P, Jagtap P, et al. Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome. Nat Microbiol. (2022) 7:680–94. doi: 10.1038/s41564-022-01103-1

PubMed Abstract | Crossref Full Text | Google Scholar

30. Liu C, He D, Yu A, Deng Y, Wang L, and Song Z. Correlation analysis between gut microbiota characteristics and melasma. Front Microbiol. (2022) 13:1051653. doi: 10.3389/fmicb.2022.1051653

PubMed Abstract | Crossref Full Text | Google Scholar

31. Park EM, Chelvanambi M, Bhutiani N, Kroemer G, Zitvogel L, and Wargo JA. Targeting the gut and tumor microbiota in cancer. Nat Med. (2022) 28:690–703. doi: 10.1038/s41591-022-01779-2

PubMed Abstract | Crossref Full Text | Google Scholar

32. Terrisse S, Zitvogel L, and Kroemer G. Impact of microbiota on breast cancer hormone therapy. Cell Stress. (2023) 7:12–9. doi: 10.15698/cst2023.03.277

PubMed Abstract | Crossref Full Text | Google Scholar

33. Chen K, Liu X, Zhao YC, Hieronymi K, Rossi G, Auvil LS, et al. Long-term administration of conjugated estrogen and bazedoxifene decreased murine fecal β-glucuronidase activity without impacting overall microbiome community. Sci Rep. (2018) 8:8166. doi: 10.1038/s41598-018-26506-1

PubMed Abstract | Crossref Full Text | Google Scholar

34. Zhao K and Hu Y. Microbiome harbored within tumors: a new chance to revisit our understanding of cancer pathogenesis and treatment. Signal Transduct Target Ther. (2020) 5:136. doi: 10.1038/s41392-020-00244-1

PubMed Abstract | Crossref Full Text | Google Scholar

35. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol. (2001) 2:361–7. doi: 10.1038/86373

PubMed Abstract | Crossref Full Text | Google Scholar

36. Baban CK, Cronin M, O'Hanlon D, O'Sullivan GC, and Tangney M. Bacteria as vectors for gene therapy of cancer. Bioeng Bugs. (2010) 1:385–94. doi: 10.4161/bbug.1.6.13146

PubMed Abstract | Crossref Full Text | Google Scholar

37. Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, and Reid G. The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol. (2016) 82:5039–48. doi: 10.1128/AEM.01235-16

PubMed Abstract | Crossref Full Text | Google Scholar

38. Jaye K, Li CG, Chang D, and Bhuyan DJ. The role of key gut microbial metabolites in the development and treatment of cancer. Gut Microbes. (2022) 14:2038865. doi: 10.1080/19490976.2022.2038865

PubMed Abstract | Crossref Full Text | Google Scholar

39. Parhi L, Alon-Maimon T, Sol A, Nejman D, Shhadeh A, Fainsod-Levi T, et al. Breast cancer colonization by Fusobacterium nucleatum accelerates tumor growth and metastatic progression. Nat Commun. (2020) 11:3259. doi: 10.1038/s41467-020-16967-2

PubMed Abstract | Crossref Full Text | Google Scholar

40. Rajput S, Volk-Draper LD, and Ran S. TLR4 is a novel determinant of the response to paclitaxel in breast cancer. Mol Cancer Ther. (2013) 12:1676–87. doi: 10.1158/1535-7163.MCT-12-1019

PubMed Abstract | Crossref Full Text | Google Scholar

41. Hieken TJ, Chen J, Hoskin TL, Walther-Antonio M, StJohnson S, Ramaker S, et al. The microbiome of aseptically collected human breast tissue in benign and Malignant disease. Sci Rep. (2016) 6:30751. doi: 10.1038/srep30751

PubMed Abstract | Crossref Full Text | Google Scholar

42. Li J, Zhu Y, Yang L, and Wang Z. Effect of gut microbiota in the colorectal cancer and potential target therapy. Discov Oncol. (2022) 13:51. doi: 10.1007/s12672-022-00517-x

PubMed Abstract | Crossref Full Text | Google Scholar

43. Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, and Nougayrède JP. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A. (2010) 107:11537–42. doi: 10.1073/pnas.1001261107

PubMed Abstract | Crossref Full Text | Google Scholar

44. Zhang S, Yang Y, Weng W, Guo B, Cai G, Ma Y, et al. Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer. J Exp Clin Cancer Res. (2019) 38:14. doi: 10.1186/s13046-018-0985-y

PubMed Abstract | Crossref Full Text | Google Scholar

45. Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol. (2016) 13:228–41. doi: 10.1038/nrclinonc.2015.215

PubMed Abstract | Crossref Full Text | Google Scholar

46. Kaetzel CS. Cooperativity among secretory IgA, the polymeric immunoglobulin receptor, and the gut microbiota promotes host-microbial mutualism. Immunol Lett. (2014) 162:10–21. doi: 10.1016/j.imlet.2014.05.008

PubMed Abstract | Crossref Full Text | Google Scholar

47. Goedert JJ, Hua X, Bielecka A, Okayasu I, Milne GL, Jones GS, et al. Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiota. Br J Cancer. (2018) 118:471–9. doi: 10.1038/bjc.2017.435

PubMed Abstract | Crossref Full Text | Google Scholar

48. Ullern A, Holm K, Røssevold AH, Andresen NK, Bang C, Lingjærde OC, et al. Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer. Mol Oncol. (2024) 19:1229–43. doi: 10.1002/1878-0261.13760

PubMed Abstract | Crossref Full Text | Google Scholar

49. Gwak JM, Jang MH, Kim DI, Seo AN, and Park SY. Prognostic value of tumor-associated macrophages according to histologic locations and hormone receptor status in breast cancer. PloS One. (2015) 10:e0125728. doi: 10.1371/journal.pone.0125728

PubMed Abstract | Crossref Full Text | Google Scholar

50. Buchta Rosean C, Feng TY, Azar FN, and Rutkowski MR. Impact of the microbiome on cancer progression and response to anti-cancer therapies. Adv Cancer Res. (2019) 143:255–94. doi: 10.1016/bs.acr.2019.03.005

PubMed Abstract | Crossref Full Text | Google Scholar

51. Lakritz JR, Poutahidis T, Mirabal S, Varian BJ, Levkovich T, Ibrahim YM, et al. Gut bacteria require neutrophils to promote mammary tumorigenesis. Oncotarget. (2015) 6:9387–96. doi: 10.18632/oncotarget.v6i11

PubMed Abstract | Crossref Full Text | Google Scholar

52. Lam KC, Araya RE, Huang A, Chen Q, Di Modica M, Rodrigues RR, et al. Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment. Cell. (2021) 184:5338–5356.e21. doi: 10.1016/j.cell.2021.09.019

PubMed Abstract | Crossref Full Text | Google Scholar

53. Hassan Z, Mustafa S, Rahim RA, and Isa NM. Anti-breast cancer effects of live, heat-killed and cytoplasmic fractions of Enterococcus faecalis and Staphylococcus hominis isolated from human breast milk. In Vitro Cell Dev Biol Anim. (2016) 52:337–48. doi: 10.1007/s11626-015-9978-8

PubMed Abstract | Crossref Full Text | Google Scholar

54. Hix LM, Shi YH, Brutkiewicz RR, Stein PL, Wang CR, and Zhang M. CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis. PloS One. (2011) 6:e20702. doi: 10.1371/journal.pone.0020702

PubMed Abstract | Crossref Full Text | Google Scholar

55. Wang H, Rong X, Zhao G, Zhou Y, Xiao Y, Ma D, et al. The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer. Cell Metab. (2022) 34:581–594.e8. doi: 10.1016/j.cmet.2022.02.010

PubMed Abstract | Crossref Full Text | Google Scholar

56. Kinjo Y, Tupin E, Wu D, Fujio M, Garcia-Navarro R, Benhnia MR, et al. Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol. (2006) 7:978–86. doi: 10.1038/ni1380

PubMed Abstract | Crossref Full Text | Google Scholar

57. Xuan C, Shamonki JM, Chung A, Dinome ML, Chung M, Sieling PA, et al. Microbial dysbiosis is associated with human breast cancer. PloS One. (2014) 9:e83744. doi: 10.1371/journal.pone.0083744

PubMed Abstract | Crossref Full Text | Google Scholar

58. Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. (2013) 341:569–73. doi: 10.1126/science.1241165

PubMed Abstract | Crossref Full Text | Google Scholar

59. Francescone R, Hou V, and Grivennikov SI. Microbiome, inflammation, and cancer. Cancer J. (2014) 20:181–9. doi: 10.1097/PPO.0000000000000048

PubMed Abstract | Crossref Full Text | Google Scholar

60. Pagano JS, Blaser M, Buendia MA, Damania B, Khalili K, Raab-Traub N, et al. Infectious agents and cancer: criteria for a causal relation. Semin Cancer Biol. (2004) 14:453–71. doi: 10.1016/j.semcancer.2004.06.009

PubMed Abstract | Crossref Full Text | Google Scholar

61. Scott AJ, Alexander JL, Merrifield CA, Cunningham D, Jobin C, Brown R, et al. International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis. Gut. (2019) 68:1624–32. doi: 10.1136/gutjnl-2019-318556

PubMed Abstract | Crossref Full Text | Google Scholar

62. Muegge BD, Kuczynski J, Knights D, Clemente JC, González A, Fontana L, et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. (2011) 332:970–4. doi: 10.1126/science.1198719

PubMed Abstract | Crossref Full Text | Google Scholar

63. Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. (2008) 25:2097–116. doi: 10.1007/s11095-008-9661-9

PubMed Abstract | Crossref Full Text | Google Scholar

64. Leeming ER, Johnson AJ, Spector TD, and Le Roy CI. Effect of diet on the gut microbiota: rethinking intervention duration. Nutrients. (2019) 11:2862. doi: 10.3390/nu11122862

PubMed Abstract | Crossref Full Text | Google Scholar

65. Ostan R, Lanzarini C, Pini E, Scurti M, Vianello D, Bertarelli C, et al. Inflammaging and cancer: a challenge for the Mediterranean diet. Nutrients. (2015) 7:2589–621. doi: 10.3390/nu7042589

PubMed Abstract | Crossref Full Text | Google Scholar

66. Martinez-Lacoba R, Pardo-Garcia I, Amo-Saus E, and Escribano-Sotos F. Mediterranean diet and health outcomes: a systematic meta-review. Eur J Public Health. (2018) 28:955–61. doi: 10.1093/eurpub/cky113

PubMed Abstract | Crossref Full Text | Google Scholar

67. Boyd NF and McGuire V. Evidence of association between plasma high-density lipoprotein cholesterol and risk factors for breast cancer. J Natl Cancer Inst. (1990) 82:460–8. doi: 10.1093/jnci/82.6.460

PubMed Abstract | Crossref Full Text | Google Scholar

68. Wu Q, Ishikawa T, Sirianni R, Tang H, McDonald JG, Yuhanna IS, et al. 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Rep. (2013) 5:637–45. doi: 10.1016/j.celrep.2013.10.006

PubMed Abstract | Crossref Full Text | Google Scholar

69. Warner M and Gustafsson JA. On estrogen, cholesterol metabolism, and breast cancer. N Engl J Med. (2014) 370:572–3. doi: 10.1056/NEJMcibr1315176

PubMed Abstract | Crossref Full Text | Google Scholar

70. Lasagna A, Zuccaro V, Ferraris E, Corbella M, Bruno R, and Pedrazzoli P. COVID-19 and breast cancer: may the microbiome be the issue. Future Oncol. (2021) 17:123–6. doi: 10.2217/fon-2020-0764

PubMed Abstract | Crossref Full Text | Google Scholar

71. Dorgan JF, Baer DJ, Albert PS, Judd JT, Brown ED, Corle DK, et al. Serum hormones and the alcohol-breast cancer association in postmenopausal women. J Natl Cancer Inst. (2001) 93:710–5. doi: 10.1093/jnci/93.9.710

PubMed Abstract | Crossref Full Text | Google Scholar

72. Etique N, Chardard D, Chesnel A, Merlin JL, Flament S, and Grillier-Vuissoz I. Ethanol stimulates proliferation, ERalpha and aromatase expression in MCF-7 human breast cancer cells. Int J Mol Med. (2004) 13:149–55. doi: 10.3892/ijmm.13.1.149

Crossref Full Text | Google Scholar

73. Wieërs G, Belkhir L, Enaud R, Leclercq S, Philippart de Foy JM, Dequenne I, et al. How probiotics affect the microbiota. Front Cell Infect Microbiol. (2019) 9:454. doi: 10.3389/fcimb.2019.00454

PubMed Abstract | Crossref Full Text | Google Scholar

74. Imani Fooladi AA, Yazdi MH, Pourmand MR, Mirshafiey A, Hassan ZM, Azizi T, et al. Th1 cytokine production induced by lactobacillus acidophilus in BALB/c mice bearing transplanted breast tumor. Jundishapur J Microbiol. (2015) 8:e17354. doi: 10.5812/jjm.8(4)2015.17354

PubMed Abstract | Crossref Full Text | Google Scholar

75. Nama A, Sandeepa GM, Buddolla V, and Mastan A. Advances in understanding therapeutic mechanisms of probiotics in cancer management, with special emphasis on breast cancer: A comprehensive review. Eur J Pharmacol. (2025) 995:177410. doi: 10.1016/j.ejphar.2025.177410

PubMed Abstract | Crossref Full Text | Google Scholar

76. Terpou A, Papadaki A, Lappa IK, Kachrimanidou V, Bosnea LA, and Kopsahelis N. Probiotics in food systems: significance and emerging strategies towards improved viability and delivery of enhanced beneficial value. Nutrients. (2019) 11:1591. doi: 10.3390/nu11071591

PubMed Abstract | Crossref Full Text | Google Scholar

77. Marschalek J, Farr A, Marschalek ML, Domig KJ, Kneifel W, Singer CF, et al. Influence of orally administered probiotic lactobacillus strains on vaginal microbiota in women with breast cancer during chemotherapy: A randomized placebo-controlled double-blinded pilot study. Breast Care (Basel). (2017) 12:335–9. doi: 10.1159/000478994

PubMed Abstract | Crossref Full Text | Google Scholar

78. Toi M, Hirota S, Tomotaki A, Sato N, Hozumi Y, Anan K, et al. Probiotic beverage with soy isoflavone consumption for breast cancer prevention: A case-control study. Curr Nutr Food Sci. (2013) 9:194–200. doi: 10.2174/15734013113099990001

PubMed Abstract | Crossref Full Text | Google Scholar

79. Chiang CJ and Huang PH. Metabolic engineering of probiotic Escherichia coli for cytolytic therapy of tumors. Sci Rep. (2021) 11:5853. doi: 10.1038/s41598-021-85372-6

PubMed Abstract | Crossref Full Text | Google Scholar

80. Kumar P, Sinha R, and Shukla P. Artificial intelligence and synthetic biology approaches for human gut microbiome. Crit Rev Food Sci Nutr. (2022) 62:2103–21. doi: 10.1080/10408398.2020.1850415

PubMed Abstract | Crossref Full Text | Google Scholar

81. Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, et al. Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods. (2019) 8:92. doi: 10.3390/foods8030092

PubMed Abstract | Crossref Full Text | Google Scholar

82. Suzuki R, Rylander-Rudqvist T, Ye W, Saji S, Adlercreutz H, and Wolk A. Dietary fiber intake and risk of postmenopausal breast cancer defined by estrogen and progesterone receptor status–a prospective cohort study among Swedish women. Int J Cancer. (2008) 122:403–12. doi: 10.1002/ijc.v122:2

PubMed Abstract | Crossref Full Text | Google Scholar

83. Zengul AG, Demark-Wahnefried W, Barnes S, Morrow CD, Bertrand B, Berryhill TF, et al. Associations between dietary fiber, the fecal microbiota and estrogen metabolism in postmenopausal women with breast cancer. Nutr Cancer. (2021) 73:1108–17. doi: 10.1080/01635581.2020.1784444

PubMed Abstract | Crossref Full Text | Google Scholar

84. Xu C, Ruan B, Jiang Y, Xue T, Wang Z, Lu H, et al. Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice. Biochem Biophys Res Commun. (2017) 488:418–24. doi: 10.1016/j.bbrc.2017.05.071

PubMed Abstract | Crossref Full Text | Google Scholar

85. Velicer CM, Heckbert SR, Lampe JW, Potter JD, Robertson CA, and Taplin SH. Antibiotic use in relation to the risk of breast cancer. JAMA. (2004) 291:827–35. doi: 10.1001/jama.291.7.827

PubMed Abstract | Crossref Full Text | Google Scholar

86. Simin J, Tamimi RM, Engstrand L, Callens S, and Brusselaers N. Antibiotic use and the risk of breast cancer: A systematic review and dose-response meta-analysis. Pharmacol Res. (2020) 160:105072. doi: 10.1016/j.phrs.2020.105072

PubMed Abstract | Crossref Full Text | Google Scholar

87. Kirkup BM, Mckee A, Makin KA, Paveley J, and Robinson SD. Perturbation of the gut microbiota by antibiotics results in accelerated breast tumour growth and metabolic dysregulation. bioRxiv. (2019). doi: 10.1101/553602

Crossref Full Text | Google Scholar

88. Hrubesz G, Leigh J, and Ng TL. Understanding the relationship between breast cancer, immune checkpoint inhibitors, and gut microbiota: a narrative review. Transl Breast Cancer Res. (2024) 5:31. doi: 10.21037/tbcr-24-14

PubMed Abstract | Crossref Full Text | Google Scholar

89. Xu S, Liu Z, Lv M, Chen Y, and Liu Y. Intestinal dysbiosis promotes epithelial-mesenchymal transition by activating tumor-associated macrophages in ovarian cancer. Pathog Dis. (2019) 77:ftz019. doi: 10.1093/femspd/ftz019

PubMed Abstract | Crossref Full Text | Google Scholar

90. Chadchan SB, Naik SK, Popli P, Talwar C, Putluri S, Ambati CR, et al. Gut microbiota and microbiota-derived metabolites promotes endometriosis. Cell Death Discov. (2023) 9:28. doi: 10.1038/s41420-023-01309-0

PubMed Abstract | Crossref Full Text | Google Scholar

91. Chen D, Wu J, Jin D, Wang B, and Cao H. Fecal microbiota transplantation in cancer management: Current status and perspectives. Int J Cancer. (2019) 145:2021–31. doi: 10.1002/ijc.v145.8

PubMed Abstract | Crossref Full Text | Google Scholar

92. Stoff R, Wolf Y, and Boursi B. Fecal microbiota transplantation as a cancer therapeutic. Cancer J. (2023) 29:102–8. doi: 10.1097/PPO.0000000000000651

PubMed Abstract | Crossref Full Text | Google Scholar

93. Xu H, Cao C, Ren Y, Weng S, Liu L, Guo C, et al. Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment. Front Immunol. (2022) 13:949490. doi: 10.3389/fimmu.2022.949490

PubMed Abstract | Crossref Full Text | Google Scholar

94. Khoruts A and Sadowsky MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. (2016) 13:508–16. doi: 10.1038/nrgastro.2016.98

PubMed Abstract | Crossref Full Text | Google Scholar

95. Dakal TC, Xu C, and Kumar A. Advanced computational tools, artificial intelligence and machine-learning approaches in gut microbiota and biomarker identification. Front Med Technol. (2024) 6:434799. doi: 10.3389/fmedt.2024.1434799

PubMed Abstract | Crossref Full Text | Google Scholar

96. Pérez-Prieto I, Vargas E, Salas-Espejo E, Lüll K, Canha-Gouveia A, Pérez LA, et al. Gut microbiome in endometriosis: a cohort study on 1000 individuals. BMC Med. (2024) 22:294. doi: 10.1186/s12916-024-03503-y

PubMed Abstract | Crossref Full Text | Google Scholar

97. Marcos-Zambrano LJ, Karaduzovic-Hadziabdic K, Loncar Turukalo T, Przymus P, Trajkovik V, Aasmets O, et al. Applications of machine learning in human microbiome studies: A review on feature selection, biomarker identification, disease prediction and treatment. Front Microbiol. (2021) 12:634511. doi: 10.3389/fmicb.2021.634511

PubMed Abstract | Crossref Full Text | Google Scholar

Keywords: breast cancer, gut microbiota, prebiotics, probiotic, dysbiosis

Citation: Kang L, Chen H, He C and Li J (2025) Effects of gut microbiota in breast cancer. Front. Oncol. 15:1617410. doi: 10.3389/fonc.2025.1617410

Received: 24 April 2025; Accepted: 13 May 2025;
Published: 17 June 2025.

Edited by:

Nosheen Masood, Fatima Jinnah Women University, Pakistan

Reviewed by:

Angioletta Lasagna, San Matteo Hospital Foundation (IRCCS), Italy
Sathiyapriya Viswanathan, ACS Medical College and Hospital, India

Copyright © 2025 Kang, Chen, He and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Junchuan Li, bGlqdW5jaHVhbjEyM0AxMjYuY29t

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