Age-diet interactions significantly influence intratumoral gene expression, gut microbiome signature and tumor microenvironment in colorectal cancer

作者：Shivani Soni, Pooja Mittal, Jae Ho Lo, Yanqing Yang, Goar Smbatyan, Keehoon Lee, Junxiang Wan, Hiroshi Kumagai, Kelvin Yen, Hemal H. Mehta, Brendan Miller, Lesly Torres‐Gonzalez, Francesca Battaglin, Unnati Hemant Shah, Michela Bartolini, Wu Zhang, David W. Craig, Joshua Millstein, Pinchas Cohen, Heinz-Josef Lenz · 发表于：Neoplasia · 年份：2025 · DOI：10.1016/j.neo.2025.101245 · 被引用次数：1 · 研究领域：Nutrition and Health in Aging、GDF15 and Related Biomarkers、Esophageal Cancer Research and Treatment

Colorectal Cancer (CRC) is the third most prevalent malignancy, leading to significant morbidity and mortality globally. Epidemiological studies suggest that chronological age and diet are among the major contributing factors correlated with the incidence of CRC. Our study aimed to provide insights into the association between age, diet, and gut microbiome in CRC using molecular techniques including RNA sequencing, cytokine analysis, and metagenomic analysis. We used syngeneic MC38 mice model divided into two age groups (old and young) and three diet groups (standard chow, calorie-restricted and high-fat). The major findings of this study are that age and diet impact intratumoral gene signaling (nuclear and mitochondrial), and hub genes we identified are associated with prognosis in CRC. Fecal microbiome analysis showed that old microbiomes have higher alpha diversity compared to young mice. Our results demonstrate that interactions between host (age) and external (diet) factors regulate tumor growth mediated by cytokines, mitochondrial derived proteins, and the gut microbiome. Collectively, our findings advance current understanding of the mechanisms by which aging, diet and gut microbiota impact CRC onset and progression though further investigation is warranted.