Acute experimental colitis in 5xFAD Alzheimer's disease mice leads to enhanced monocyte infiltration into the brain accompanied by reduced β-amyloid deposition.

INTRODUCTION

Emerging evidence has connected Alzheimer's disease (AD) to systemic inflammation, intestinal abnormalities, and altered gut microbiota, highlighting the significance of the gut-brain axis. Here, we investigated the impact of acute experimental colitis (acute colitis) on AD pathology.

METHODS

Acute colitis was induced in 2-month-old 5xFAD mice using dextran sodium sulfate (DSS) to assess the effects of intestinal inflammation on the microbiome, systemic inflammation, neuroinflammation, and beta-amyloid deposition.

RESULTS

Induction of acute colitis in 5xFAD mice led to microbial dysbiosis and systemic inflammation. As a result, monocyte infiltration was observed in the brain accompanied by reduced cerebral beta-amyloid deposition and increased beta-amyloid efflux into the bloodstream.

DISCUSSION

Increased infiltration of monocytes and elevated beta-amyloid release into the bloodstream could both be responsible for the reduced beta-amyloid deposition in 5xFAD mice following acute colitis. These results further highlight an important connection between gut-induced peripheral inflammation and the progression of AD.

HIGHLIGHTS

Microbial dysbiosis occurs as a result of acute colitis in 5xFAD mice. Acute colitis in 5xFAD mice affects beta-amyloid deposition. Increased IL-2 and IL-6 cytokine levels in the hippocampus of 5xFAD colitis mice. Colitis in 5xFAD mice increases serum proinflammatory cytokine levels and endotoxins. Acute colitis in 5xFAD mice increases monocyte infiltration and serum beta-amyloid.