Inhibition of colorectal cancer in Alzheimer’s disease is mediated by gut microbiota via induction of inflammatory tolerance

作者：Nan Zhang, Rui Zhang, Lei Jiang, Zhaoyu Gao, Wenzhen Xia, Xiaoying Ma, Yushi Qin, Di Zhang, Jiazhen Li, Pei Tian, Qi Zhang, Wanchang Wang, Kaixia Zhang, Shan Xu, Shan Xu, Na Zhao, Shunjiang Xu, Shunjiang Xu · 发表于：Proceedings of the National Academy of Sciences · 年份：2024 · DOI：10.1073/pnas.2314337121 · 被引用次数：15 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Clostridium difficile and Clostridium perfringens research

Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer’s disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane–dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella , were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella -derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella -derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tol...