Effects of alcohol on gut microbiome in adolescent and adult MMTV-Wnt1 mice

Hui Li^1,2Leeann Aguilar Meza³Shailesh K Shahi²Zuohui Zhang²Wen Wen²Di Hu²Hong Lin²Ashutosh K Mangalam²Jia Luo^2*

• ¹The University of Iowa, Iowa City, United States
• ²Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States
• ³Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States

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) that reside in the gastrointestinal tract-plays a pivotal role in systemic health and disease. The microbiome exerts its influence by regulating key physiological processes such as metabolism, immune function, and inflammatory responses. Disruption of the gut microbiome (dysbiosis) has been implicated in breast cancer development. We hypothesized that binge-like alcohol exposure induces gut dysbiosis, which in turn drives systemic inflammation and carcinogenic processes. Previously, we demonstrated that intraperitoneal binge-like 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 binge-like intraperitoneal 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 both adolescent and adult mice of 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. This provides insights into the potential role of gut dysbiosis in alcohol-induced mammary tumor promotion and offering avenues for future research.