ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1563224
This article is part of the Research TopicUncovering Microbial Biomarkers and Interventions in Colorectal Cancer: a Transformative Journey from Pathogenesis to TherapyView all articles
Intermittent fasting inhibits the development of colorectal cancer in APC Min/+ mice through gut microbiota and its related metabolites
Provisionally accepted
- Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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Background and Objectives: 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.Methods: First, Apc Min/+ 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, in vitro 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.compared to the control group (1.25 ± 0.38 vs 2.50 ± 0.38 tumors/mouse, P = 0.017) and markedly attenuated tumor progression. 16S rRNA sequencing analysis revealed significant enrichment of two key bacterial genera, Alistipes (P = 0.030) and Odoribacter (P = 0.030), along with a significant reduction in fecal isovaleric acid levels (P < 0.05) in the intermittent fasting group. Furthermore, intermittent fasting effectively controlled body weight gain (P < 0.05) and significantly improved intestinal barrier function (P < 0.05). In vitro experiments further demonstrated that isovaleric acid directly promoted CRC cell proliferation (P < 0.05) and enhanced their invasive capacity (P < 0.05).Intermittent fasting suppresses CRC development in mice through its effects on gut microbiota and related metabolites.
Keywords: colorectal cancer, intermittent fasting, gut microbiome, isovaleric acid, Apc mice Min/+
Received: 20 Jan 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 Chen, chen and Su. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: jiong chen, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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