Differential Effects of High-Fiber and Low-Fiber Diets on Antitumor Immunity and Colon Tumor Progression in a Murine Model.

Kevin E Goggin, SeonYeong Jamie Seo, Benjamin G Wu, Sinisa Ivelja, Matthias C Kugler, Miao Chang, Fares Darawshy, Yonghua Li, Cecilia J Chung, Yaa Kyeremateng, Jun-Chieh J Tsay, Shivani Singh, Daniel H Sterman, Leopoldo N Segal, Nejat K Egilmez, Qingsheng Li
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Abstract

The role of dietary fiber in colon cancer prevention remains controversial. We investigated its impact on antitumor immunity and the gut microbiota in APCmin/+ mice infected with enterotoxigenic Bacteroides fragilis. Mice were fed high-fiber, low-fiber, or chow diets, and the tumor burden, survival, cytokines, microbiota, and metabolites were analyzed. Contrary to the belief that high fiber inhibits tumor progression, it had no significant impact compared with chow diet. However, the low-fiber diet significantly reduced the tumor burden and improved survival. Mechanistically, high fiber increased proinflammatory cytokines and CD4+Foxp3+RORγt+IL-17A+ regulatory T cells, whereas low fiber enhanced anti-inflammatory cytokines and cytotoxic T cells. High fiber enriched microbial taxa associated with IL-17A+RORγt+ regulatory T cells and altered metabolites, including reduced tryptophan and increased short-chain fatty acids and bile acids. Low fiber produced opposite effects. These findings suggest that dietary fiber's effects on colon cancer depends on microbial infection and immune status, emphasizing the need for personalized dietary interventions in colon cancer management. Prevention Relevance: Dietary fiber's impact on colon cancer progression highlights the need for personalized dietary approaches, considering microbial infection and immune status.

高纤维和低纤维饮食对小鼠抗肿瘤免疫和结肠肿瘤进展的不同影响
膳食纤维在预防结肠癌中的作用仍然存在争议。我们研究了其对APCmin/+小鼠感染肠产毒素脆弱拟杆菌后抗肿瘤免疫和肠道微生物群的影响。小鼠分别被喂食高纤维、低纤维或鼠粮,并分析肿瘤负荷、存活率、细胞因子、微生物群和代谢物。与高纤维抑制肿瘤进展的观点相反,高纤维与鼠粮相比没有显著的影响。然而,低纤维饮食显著减少了肿瘤负担,提高了生存率。高纤维增加促炎细胞因子和CD4+Foxp3+RORγt+IL-17A+调节性T细胞,低纤维增加抗炎细胞因子和细胞毒性T细胞。高纤维富集的微生物类群与IL-17A+ rorγ - t+ Tregs和代谢产物改变相关,包括色氨酸减少、短链脂肪酸和胆汁酸增加。低纤维则产生相反的效果。这些发现表明,膳食纤维对结肠癌的影响取决于微生物感染和免疫状态,强调了在结肠癌管理中个性化饮食干预的必要性。
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