Chen Jia, Su Rishun, He Yulong, Chen Jiong
Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, China.
Department of Anesthesiology, The Seventh Affiliated Hospital of Sun Yat-sen University, School of Medicine, Sun Yat-sen University, Shenzhen, Guangdong, China.
Front Microbiol. 2025 May 29;16:1563224. doi: 10.3389/fmicb.2025.1563224. eCollection 2025.
Intermittent fasting is an emerging dietary approach, but its specific role in colorectal cancer (CRC) is not yet clear. In this study, we investigated the relationship between intermittent fasting and colorectal development in mice.
First, APC mouse models (a spontaneous model of colorectal cancer) were subjected to intermittent fasting intervention (2 days/week) with regular monitoring of body weight changes. Subsequently, 16S rRNA sequencing and untargeted metabolomics were employed to analyze alterations in fecal microbial community structure and metabolic profiles following the fasting intervention. Tumor development was quantitatively assessed by enumerating CRC lesions using HE staining, while histopathological evaluation was performed to determine the degree of neoplastic progression. Concurrently, western blotting was conducted to examine the expression levels of intestinal barrier function-related proteins. Finally, validation experiments, including colony formation assay and transwell invasion assay, were performed to investigate the effects of the key microbial metabolite isovaleric acid on the proliferative and invasive capacities of CRC cells.
Intermittent fasting significantly reduced tumor incidence by approximately 50% compared to the control group (1.25 ± 0.38 vs 2.50 ± 0.38 tumors/mouse, = 0.017) and markedly attenuated tumor progression. 16S rRNA sequencing analysis revealed significant enrichment of two key bacterial genera, (P = 0.030) and ( = 0.030), along with a significant reduction in fecal isovaleric acid levels ( < 0.05) in the intermittent fasting group. Furthermore, intermittent fasting effectively controlled body weight gain ( < 0.05) and significantly improved intestinal barrier function ( < 0.05). experiments further demonstrated that isovaleric acid directly promoted CRC cell proliferation ( < 0.05) and enhanced their invasive capacity ( < 0.05).
Intermittent fasting suppresses CRC development in mice through its effects on gut microbiota and related metabolites.
间歇性禁食是一种新兴的饮食方式，但其在结直肠癌（CRC）中的具体作用尚不清楚。在本研究中，我们调查了间歇性禁食与小鼠结直肠癌发生发展之间的关系。
首先，对APC小鼠模型（一种结直肠癌自发模型）进行间歇性禁食干预（每周2天），并定期监测体重变化。随后，采用16S rRNA测序和非靶向代谢组学分析禁食干预后粪便微生物群落结构和代谢谱的变化。通过苏木精-伊红（HE）染色计数CRC病变来定量评估肿瘤发展情况，同时进行组织病理学评估以确定肿瘤进展程度。此外，进行蛋白质免疫印迹法检测肠道屏障功能相关蛋白的表达水平。最后，进行包括集落形成试验和Transwell侵袭试验在内的验证实验，以研究关键微生物代谢产物异戊酸对CRC细胞增殖和侵袭能力的影响。
与对照组相比，间歇性禁食显著降低了约50%的肿瘤发生率（1.25±0.38个肿瘤/小鼠 vs 2.50±0.38个肿瘤/小鼠，P = 0.017），并显著减缓了肿瘤进展。16S rRNA测序分析显示，间歇性禁食组中两个关键细菌属显著富集（P = 0.030），粪便异戊酸水平显著降低（P < 0.05）。此外，间歇性禁食有效控制了体重增加（P < 0.05），并显著改善了肠道屏障功能（P < 0.05）。验证实验进一步表明，异戊酸直接促进了CRC细胞增殖（P < 0.05）并增强了其侵袭能力（P < 0.05）。
间歇性禁食通过对肠道微生物群及其相关代谢产物的影响抑制小鼠CRC的发展。
