Fecal Microbiota Transplantation from APP/PS1 Mice Induces Th17-Related Inflammatory Parameters and Pathological Changes in the Gut–Brain Axis of Healthy C57BL/6J Mice

TL;DR

Transferring gut microbes from Alzheimer's model mice to healthy mice caused gut and brain inflammation linked to Th17 cells.

Contribution

Shows AD-associated gut microbiota can induce central inflammation and Th17-related changes in healthy mice via the gut-brain axis.

Findings

AD-FMT caused ileal inflammation and central inflammation in healthy mice.

Th17-related factors and RORγt mRNA were upregulated after AD-FMT.

Specific gut bacteria correlated with Th17 inflammatory markers.

Abstract

The gut–brain axis is increasingly implicated in Alzheimer’s disease (AD) pathogenesis, but the potential correlation between AD-associated gut microbiota and central inflammation remains largely unclear. This study aimed to explore their correlative link, with a focus on changes and involvement of Th17 cell-related factors in the gut–brain axis. Healthy C57BL/6J mice were pretreated with antibiotics for 1 week to deplete the indigenous gut microbiota, followed by 2 weeks of fecal microbiota transplantation (FMT) using feces from APP/PS1 AD model mice. Hematoxylin–eosin (H&E) staining, ELISA, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), 16S rDNA sequencing, and correlation analysis were performed to evaluate ileal and central pathological changes, Th17 cell-related inflammatory mediators, ileal microbiota composition, and their potential correlations. The results demonstrated that AD-FMT significantly induced ileal inflammatory infiltration and central inflammation in recipient mice, which was accompanied by abnormal expression of Th17 cell-related indicators, elevated levels of Th17-associated inflammatory factors, upregulated RORγt mRNA expression, and perturbed ileal microbiota composition. Correlation analysis further suggested that specific ileal bacterial taxa were closely correlated with Th17 cell-related inflammatory factors. These findings suggest a potential correlation between AD-associated microbiota and central inflammation, possibly by regulating intestinal Th17 cell-related indicators and altering gut microbial composition. This study provides correlative evidence supporting the involvement of the gut–brain axis in AD-related pathogenesis, highlighting the link between gut microbiota, central inflammation and Th17-related factors.

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