Li Hui, Aguilar Meza Leeann, Shahi Shailesh K, Zhang Zuohui, Wen Wen, Hu Di, Lin Hong, Mangalam Ashutosh, Luo Jia
bioRxiv. 2025 Mar 17:2025.03.17.643801. doi: 10.1101/2025.03.17.643801.
Breast cancer is the most commonly diagnosed cancer in women worldwide, with alcohol consumption recognized as a significant risk factor. While epidemiological studies consistently show a positive correlation between alcohol consumption and increased breast cancer risk, the underlying mechanisms remain unclear. Recent evidence suggests that the gut microbiome-the diverse collection of microorganisms, including bacteria, viruses, and fungi, residing in the gastrointestinal tract-plays a pivotal role in systemic health and disease. This is achieved through its regulation of key physiological processes such as metabolism, immune function, and inflammatory responses. Disruption of the gut microbiome (dysbiosis) has recently been implicated in the development of breast cancer. We hypothesized that alcohol exposure induces gut dysbiosis, which in turn drives systemic inflammation and carcinogenic processes. Previously, we demonstrated that alcohol exposure promotes mammary tumor growth and aggressiveness in MMTV-Wnt1 (Wnt1) transgenic mice, an established model for investigating mechanisms of alcohol-induced tumor promotion. In this study, we sought to determine whether alcohol exposure induces gut dysbiosis in adolescent and adult Wnt1 transgenic mice and their wild-type FVB counterparts. Our findings revealed that alcohol exposure significantly reduced microbiome richness in adult Wnt1 and FVB mice. Alcohol exposure also markedly altered microbiome composition in adolescents and adults in both strains. Additionally, we identified specific microbial taxa that were significantly affected by alcohol exposure. These results demonstrate that alcohol disrupts the gut microbiome in a preclinical breast cancer model, providing insights into the potential role of gut dysbiosis in alcohol-induced mammary tumor promotion and offering avenues for future research.
乳腺癌是全球女性中最常被诊断出的癌症，饮酒被认为是一个重要的风险因素。虽然流行病学研究一直表明饮酒与乳腺癌风险增加之间存在正相关，但潜在机制仍不清楚。最近的证据表明，肠道微生物群（存在于胃肠道中的包括细菌、病毒和真菌在内的多种微生物集合）在全身健康和疾病中起着关键作用。这是通过其对新陈代谢、免疫功能和炎症反应等关键生理过程的调节来实现的。肠道微生物群的破坏（生态失调）最近被认为与乳腺癌的发生有关。我们假设酒精暴露会诱发肠道生态失调，进而引发全身炎症和致癌过程。此前，我们证明酒精暴露会促进MMTV-Wnt1（Wnt1）转基因小鼠的乳腺肿瘤生长和侵袭性，这是一种用于研究酒精诱导肿瘤促进机制的成熟模型。在本研究中，我们试图确定酒精暴露是否会在青春期和成年Wnt1转基因小鼠及其野生型FVB对照小鼠中诱发肠道生态失调。我们的研究结果显示，酒精暴露显著降低了成年Wnt1和FVB小鼠的微生物群丰富度。酒精暴露还显著改变了两个品系青少年和成年小鼠的微生物群组成。此外，我们确定了受酒精暴露显著影响的特定微生物分类群。这些结果表明，在临床前乳腺癌模型中酒精会破坏肠道微生物群，为肠道生态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，并为未来研究提供了途径。
