Fecal microbiota transplantation attenuates Alzheimer’s disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation

• Published in: Behavioral and brain functions Vol. 21; no. 1; pp. 2 - 21
• Main Authors: Li, Xiang, Ding, Qingyong, Wan, Xinxin, Wu, Qilong, Ye, Shiqing, Lou, Yongliang
• Format: Journal Article
• Language: English
• Published: England BioMed Central 08.01.2025; BMC
• Subjects: Alzheimer Disease - microbiology; Alzheimer Disease - therapy; Alzheimer's disease; Amyloid beta-Protein Precursor - genetics; Animals; Brain research; Cognitive ability; Cytokines; Dementia disorders; Design of experiments; Disease; Disease Models, Animal; Dysbacteriosis; Ethanol; Fecal microbiota transplantation; Fecal Microbiota Transplantation - methods; Fecal microflora; Feces; Gastrointestinal Microbiome - physiology; Gut-brain axis; Hypotheses; Inflammation; Inflammation - metabolism; Inflammation - therapy; Intestinal microbiota; Intestinal microflora; Investigations; Laboratory animals; Male; Memory; Metabolites; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microbiota; Microbiota-gut-brain axis; Mutation; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; Neurodegenerative diseases; NF-kappa B - metabolism; NF-κB protein; Pathogenesis; Permeability; Presenilin 1; Presenilin-1 - genetics; Short-chain fatty acids; Signal transduction; Signal Transduction - physiology; Software; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Transgenic animals; Transgenic mice; Transplantation; Transplants & implants; Tumor necrosis factor-TNF; Short-chain fatty acids; Microbiota-gut-brain axis; Inflammation; Alzheimer’s disease; Fecal microbiota transplantation; Intestinal microbiota
• ISSN: 1744-9081; 1744-9081
• DOI: 10.1186/s12993-024-00265-8

Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.