Li Hui, Meza Leeann Aguilar, Shahi Shailesh K, Zhang Zuohui, Wen Wen, Hu Di, Lin Hong, Mangalam Ashutosh K, Luo Jia
Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, United States.
Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States.
Front Oncol. 2025 Jul 16;15:1557040. doi: 10.3389/fonc.2025.1557040. eCollection 2025.
Breast cancer is the most frequently diagnosed cancer in women worldwide. Alcohol consumption is a significant and modifiable risk factor, yet the mechanisms linking alcohol to breast cancer progression remain unclear. Recent evidence suggests that the gut microbiome-a complex ecosystem that modulates metabolism, immunity, and inflammation-may act as a mediator of alcohol-induced tumor promotion. We hypothesized that binge-like alcohol exposure induces gut dysbiosis, which in turn drives systemic inflammation and carcinogenic processes.
We utilized MMTV-Wnt1 transgenic mice, a well-established model for mammary tumor development, along with wild-type FVB mice. Adolescent and adult female mice were administered binge-like doses of ethanol via intraperitoneal injection. Fecal samples were collected and analyzed by 16S rRNA gene sequencing to assess microbial diversity, composition, and taxonomic changes in response to alcohol exposure.
Binge-like alcohol exposure significantly reduced gut microbial richness in adult Wnt1 and FVB mice. In both adolescent and adult mice, alcohol markedly altered the composition of the gut microbiota across both strains. Differential abundance analysis identified specific microbial taxa significantly impacted by ethanol treatment, suggesting targeted perturbations of the gut microbial community.
Our findings demonstrate that intraperitoneal binge-like alcohol exposure induces gut dysbiosis in both tumor-prone and wild-type mice. These alterations in the gut microbiome may contribute to the pro-inflammatory and tumor-promoting effects of alcohol in breast tissue. This study provides insights into the potential role of gut dysbiosis in alcohol-induced mammary tumor promotion and offers avenues for future research.
乳腺癌是全球女性中最常被诊断出的癌症。饮酒是一个重要且可改变的风险因素，然而酒精与乳腺癌进展之间的联系机制仍不清楚。最近的证据表明，肠道微生物群——一个调节新陈代谢、免疫和炎症的复杂生态系统——可能是酒精诱导肿瘤促进作用的介导者。我们假设，类似暴饮的酒精暴露会导致肠道菌群失调，进而引发全身炎症和致癌过程。
我们使用了MMTV-Wnt1转基因小鼠，这是一种成熟的乳腺肿瘤发展模型，以及野生型FVB小鼠。通过腹腔注射给青春期和成年雌性小鼠给予类似暴饮剂量的乙醇。收集粪便样本并通过16S rRNA基因测序进行分析，以评估酒精暴露后微生物多样性、组成和分类学变化。
类似暴饮的酒精暴露显著降低了成年Wnt1和FVB小鼠的肠道微生物丰富度。在青春期和成年小鼠中，酒精均显著改变了两种品系小鼠的肠道微生物群组成。差异丰度分析确定了受乙醇处理显著影响的特定微生物分类群，表明肠道微生物群落受到了靶向干扰。
我们的研究结果表明，腹腔内类似暴饮的酒精暴露会在易患肿瘤的小鼠和野生型小鼠中诱导肠道菌群失调。肠道微生物群的这些改变可能有助于酒精在乳腺组织中的促炎和肿瘤促进作用。本研究为肠道菌群失调在酒精诱导的乳腺肿瘤促进中的潜在作用提供了见解，并为未来的研究提供了途径。
