流行病学研究表明，阿尔茨海默病 (AD) 的发病率与包括结直肠癌 (CRC) 在内的各种癌症之间呈负相关。我们的目的是确定 AD 样小鼠的 CRC 发病率是否降低，以及肠道微生物群是否通过使用 16S 核糖体 RNA 基因测序和粪便微生物群移植 (FMT) 诱导炎症耐受来赋予对肿瘤发生的抵抗力。与对照小鼠相比，AD 样小鼠由氧化偶氮甲烷-葡聚糖硫酸钠诱导的 CRC 肿瘤发生率显着降低，这通过抑制肠道炎症来证明。然而，年龄匹配的对照小鼠的 FMT 逆转了对 CRC 肿瘤发生和 AD 样小鼠炎症反应的抑制作用。肠道微生物群中的关键细菌属（包括普氏菌属）在 AD 样小鼠和遗忘性轻度认知障碍 (aMCI) 患者中均有所增加，但在 CRC 患者中有所减少。用低剂量普雷沃氏菌衍生的脂多糖 (LPS) 预处理可在体内和体外诱导炎症耐受性，并抑制小鼠结直肠癌的肿瘤发生。肠道微生物群失衡增加了肠道屏障的通透性，从而促进 LPS 从肠道吸收到血液中，导致 AD 样小鼠和 aMCI 患者的认知能力下降。这些数据表明，肠道普雷沃氏菌来源的 LPS 通过在 AD 存在的情况下诱导炎症耐受来发挥对 CRC 肿瘤发生的抵抗作用。这些发现提供了生物学证据，证明 AD 和 CRC 的发病率之间存在反比关系。

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 tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.