Inhibition of colorectal cancer in Alzheimer's disease is mediated by gut microbiota via induction of inflammatory tolerance
- PMID: 39226363
- PMCID: PMC11406296
- DOI: 10.1073/pnas.2314337121
Inhibition of colorectal cancer in Alzheimer's disease is mediated by gut microbiota via induction of inflammatory tolerance
Abstract
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.
Keywords: Alzheimer’s disease (AD); LPS; colorectal cancer (CRC); gut microbiota; inflammatory tolerance.
Conflict of interest statement
Competing interests statement:The authors declare no competing interest.
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- 82100863/MOST | National Natural Science Foundation of China (NSFC)
- H2020206105/Hebei Natural Science Foundation
- H2018206358/Hebei Natural Science Foundation
- C20210346/Funding project for introducing overseas students of Hebei Province
- 20211628/Medical Science Research Project of Hebei Province
- ZF2023029/Hebei Province Government-funded Excellent Talents Project in Clinical Medicine
- 20377707D/The Science and Technology project of the People's Livelihood in Hebei Province
- 206Z7701G/Special Funding for Local Science and Technology Development Guided by the Central Government
- 2019-I2M-5-055/CAMS Innovation Fund for Medical Sciences
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