Breast cancer is the most prevalent form of cancer and one of the leading causes of death among women (Ahmad, 2019). Currently, the primary method of treating breast cancer is through surgical mastectomy (Trayes and Cokenakes, 2021; Maughan et al., 2010). During radical breast cancer surgery, inadequate aseptic procedures or a patient’s weakened immune system may result in postoperative complications such as wound infections and delayed wound healing (Sørensen et al., 2002). In recent years, endoscopic surgery has emerged as a minimally invasive technique in breast surgery (Lee et al., 2006; Lai et al., 2016). Compared to traditional open surgery, endoscopic surgery offers the benefits of reduced trauma, faster recovery, and fewer complications (Lai et al., 2016). In particular, the application of endoscopic technology in breast cancer surgery has provided patients with more options and improved treatment outcomes (Lai et al., 2016). However, further research is needed to fully understand the health implications of endoscopic surgery.

The intestinal tract is a symbiotic environment for bacteria, and the gut microbiota plays a crucial role in maintaining overall body health (Thursby and Juge, 2017). The gut microbiota produces a vast array of metabolites that interact with the host (Thursby and Juge, 2017). Breast cancer patients typically exhibit low microbial diversity and changes in microbial composition (Plaza-Díaz et al., 2019). Specifically, breast cancer patients had been found to have elevated levels of Clostridiaceae, Calcobacterium faecalis, and Ruminalococcaceae, and lower levels of Daueriaceae and Hirschsprungiaceae (Fernández et al., 2018). The degree of deterioration in breast cancer patients was found to be negatively correlated with Faecalibacterium prausnitzii and interleukin-6 levels (Ma et al., 2020). Additionally, research had shown that gut microbes are involved in estrogen metabolism, which is closely linked to the development of breast cancer (Parida and Sharma, 2019). However, the impact of gut microbiota on breast cancer prognosis remains largely unknown.

Studies have shown that surgery, particularly abdominal surgery, can disrupt the balance of gut microbiota (Guyton and Alverdy, 2017). This disruption can affect postoperative recovery and the incidence of complications by altering the gut microbiota (Lederer et al., 2021). A recent study has demonstrated that traditional mastectomy surgery can alter the composition and metabolites of gut microbiota (Fan et al., 2024). Therefore, this study aims to further investigate the impact of endoscopic surgery on gut microbiota, as well as the differences between endoscopic surgery and traditional mastectomy surgery in terms of their effects on gut microbiota.

Evidence from prior studies underscores the profound impact of surgical intervention on the intestinal ecosystem. Surgery for colorectal cancer has been found to modify the composition of bacterial groups, including bifidobacteria and lactobacilli (Zaharuddin et al., 2019). Changes in perioperative microbiota during cardiac surgery have been shown to impact prognosis (Chernevskaya et al., 2021). Following liver transplantation, the microbiota plays a crucial role in immunity and metabolism, which correlates with overall health (Ancona et al., 2021; Bromberg et al., 2015). Open surgeries for breast cancer have also been found to induce substantial alterations in the microbiota (Fan et al., 2024). Against this backdrop, our investigation specifically targets the underexplored terrain of endoscopic surgery—a minimally invasive approach—and its repercussions on the gut microbiota and metabolites.

Our current investigation solidifies the premise that endoscopic surgery exerts a notable effect on both the beta diversity and compositional profile of the gut microbiota, reaffirming surgery’s status as a potent modifier of gut ecology. Specifically, our results revealed a striking diminution in the Firmicutes to Bacteroidetes ratio among individuals undergoing endoscopic surgery for breast cancer. This finding aligns closely with observations from a study demonstrating reduced Firmicutes to Bacteroidetes ratios in breast cancer survivors versus healthy counterparts (Caleca et al., 2023), further underscoring surgery’s role in reconfiguring microbial landscapes. In a cohort with a history of chemotherapy, higher levels of fear of cancer recurrence were associated with lower microbial diversity, lower relative abundance of Firmicutes, and higher relative abundance of Bacteroidetes (Okubo et al., 2020). Adjuvant letrozole and radiotherapy resulted in a shift in the gut microbial dominance from Firmicutes to Bacteroidetes (Vilhais et al., 2024). Recent research has shown that surgery leads to a decrease in the abundance of Firmicutes and Lachnospiraceae (Fan et al., 2024). Therefore, our study enriches our comprehension of post-breast-cancer treatment microbiome alterations.

This study found that endoscopic surgery led to a significant increase in the abundance of Oscillospirales, and a reduction in the abundance of the Lachnospiraceae and Monoglobaceae. Oscillospirales are considered as potential next-generation probiotic candidates (Murtaza et al., 2024). Oscillospira is negatively correlated with obesity, obesity-related chronic inflammation, and metabolic diseases (Yang et al., 2021). The abundance of Oscillospirales is positively correlated with low body mass index and can be used as an indicator for predicting the development of childhood obesity (Chen et al., 2020). Members of the Lachnospiraceae family primarily influence the host by producing short-chain fatty acids, and converting primary bile acids into secondary bile acids (Cesic et al., 2023; Telle-Hansen et al., 2022; Borton et al., 2017). Several studies have shown that the reduction of Lachnospiraceae is associated with various conditions such as allergies, inflammatory bowel disease, and metabolic disorders (Liu et al., 2023; Thipart et al., 2023; Huang et al., 2023). Lachnospiraceae and its metabolite butyric acid have significant anti-inflammatory effects, which can regulate immune responses, reduce inflammatory reactions, and promote the differentiation of CD4⁺ T cells into regulatory T cells (Cesic et al., 2023; Sun et al., 2022). The relative abundance of Lachnospiraceae in the intestines of breast cancer patients decreased (Di Modica et al., 2021; Donati Zeppa et al., 2023). A study showed that the decline in the abundance of Monoglobaceae bacteria in the elderly may affect their immune response (Gamez-Macias et al., 2024). Therefore, after breast cancer patients have received treatment, they may need to adjust their diet or use drug intervention to affect the abundance of gut microbiota after receiving treatment.

Our research has revealed significant shifts in gut metabolites of breast cancer patients after endoscopic surgery, marked by enriched bile secretion, cholesterol metabolism, and ascorbate and aldarate metabolism. Bile acids and their derivatives have been shown to inhibit various tumor cell lines, including colon cancer, breast cancer, pancreatic cancer and leukemia (Zhu et al., 2022; Wu et al., 2022; Wang et al., 2022). Lithocholic acid (LCA) can inhibit the adipogenesis of breast cancer cells and induce apoptosis of these cells through its putative cytotoxic effects (Kovacs et al., 2019). Bile acids signal through their receptors such as farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (TGR5) (Baumeister et al., 2024). FXR agonism by the bile acid mimetic known commercially as ocaliva, or obeticholic acid, significantly reduced breast cancer progression and overall tumor burden in a pre-clinical model (Joseph et al., 2024). In breast cancer, cholesterol and its metabolites have been found to promote tumor progression (Zeng et al., 2024). Hypercholesterolemia is considered a risk factor for estrogen receptor positive breast cancer and is associated with decreased tumor response to endocrine therapy (Nelson et al., 2013). In addition, obesity and altered lipid metabolism are also one of the risk factors for breast cancer in premenopausal and postmenopausal women, partly due to the effect of cholesterol on biophysical properties of cell membranes and the impact of these changes on signaling events initiated on membranes (McDonnell et al., 2014). Cholesterol metabolites such as 27-hydroxycholesterol play a particularly significant role in breast cancer. 27-hydroxycholesterol can not only promote the growth of estrogen receptor-positive breast cancer cells, but also stimulate cell proliferation and metastasis in several breast cancer models (Vini et al., 2022; DeRouen et al., 2023). Furthermore, 27-hydroxycholesterol functions as an endogenous regulator of lipid metabolism by interacting with nuclear liver X receptor (LXR) α and LXR β. It inhibits the anti-tumor immune response and recruits pro-angiogenic and immunosuppressive neutrophils, thereby promoting tumor progression (Molostvov et al., 2023; Krawczynska et al., 2024). The metabolism of ascorbate and aldarate involves multiple proteins and metabolites, which are metabolized in the cytoplasm and endoplasmic reticulum. By modulating these pathways, the level of ascorbate can be controlled, thereby influencing the growth and survival of tumor cells (Sanookpan et al., 2023). Ascorbic acid exerts its anticancer activity through two main mechanisms: induction of oxidative stress by hydrogen peroxide and DNA demethylation mediated by the activation of eleven translocase enzymes (Steers et al., 2023; Zarakowska et al., 2024). This suggests that ascorbic acid may have a role in cancer treatment through different biological pathways, including direct cytotoxic effects and indirect effects on genome stability (Zarakowska et al., 2024). Therefore, endoscopic surgery may impact the metabolic function of gut microbiota in breast cancer patients, which in turn may affect the prognosis.

In conclusion, although endoscopic surgery has a certain impact on the intestinal microbial diversity of breast cancer patients, there is only a slight change in the β diversity of intestinal microorganisms before and after surgery. However, there is still a significant difference between the groups, indicating that surgery may lead to a partial change in the composition of microorganisms. After surgery, the proportion of some bacterial groups, such as Firmicutes and Bacteroidetes, changed significantly, especially in the QJ3 and QJ7 groups. Furthermore, the types and quantities of metabolites produced by patients’ gut microbes have also changed. Although the current study provides us with some preliminary understanding of the impact of endoscopic surgery on the gut microbes of breast cancer patients, the specific mechanisms and long-term effects still require further in-depth study.