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早期生活补充剂改变肠道微生物群,并抑制小鼠晚年的早发性肠道肿瘤发生。

Supplementation during Early Life Alters Gut Microbiota and Inhibits Young-Onset Intestinal Tumorigenesis in Mice Later in Life.

机构信息

Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.

Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.

出版信息

Nutrients. 2024 Jul 25;16(15):2408. doi: 10.3390/nu16152408.

Abstract

Young-onset colorectal cancer is an increasing concern worldwide due to the growing prevalence of Westernized lifestyles in childhood and adolescence. Environmental factors during early life, particularly early-life nutrition, significantly contribute to the increasing incidence. Recently, there have been reports of beneficial effects, including anti-inflammation and anti-cancer, of a unique fungus (, AC) native to Taiwan. The objective of this study is to investigate the impact of AC supplementation in early life on the development of young-onset intestinal tumorigenesis. mice were fed with a high-fat diet (HF) at 4-12 weeks of age, which is equivalent to human childhood/adolescence, before switching to a normal maintenance diet for an additional 12 weeks up to 24 weeks of age, which is equivalent to young to middle adulthood in humans. Our results showed that the body weight in the HF groups significantly increased after 8 weeks of feeding ( < 0.05). Following a switch to a normal maintenance diet, the change in body weight persisted. AC supplementation significantly suppressed tumor incidence and multiplicity in females ( < 0.05) and reduced IGF-1 and Wnt/β-catenin signaling ( < 0.05). Moreover, it altered the gut microbiota, suppressed inflammatory responses, and created a microenvironment towards suppressing tumorigenesis later in life.

摘要

早发性结直肠癌是一个全球性的关注问题,这是由于儿童和青少年时期西方化生活方式的流行程度不断增加。生命早期的环境因素,特别是生命早期的营养,对发病率的上升有重要影响。最近,有报道称一种原产于中国台湾的独特真菌(,AC)具有有益的作用,包括抗炎和抗癌作用。本研究旨在探讨生命早期补充 AC 对早发性肠道肿瘤发生的影响。4-12 周龄的小鼠接受高脂肪饮食(HF)喂养,相当于人类的儿童/青少年时期,然后在 24 周龄前切换到正常维持饮食,相当于人类的年轻到中年时期。我们的结果表明,HF 组的体重在喂养 8 周后显著增加(<0.05)。切换到正常维持饮食后,体重变化仍持续存在。AC 补充显著抑制了雌性小鼠的肿瘤发生率和多发性(<0.05),并降低了 IGF-1 和 Wnt/β-catenin 信号(<0.05)。此外,它改变了肠道微生物群,抑制了炎症反应,并创造了一个有利于抑制肿瘤发生的微环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9872/11314251/9a27a1dd08bc/nutrients-16-02408-g001.jpg

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