Abstract Severe neuroinflammation is a key feature of Alzheimer’s disease (AD). Emerging evidences have suggested that its origins may lie partly in the gut. The “microbiome-gut-brain axis” provides a basic framework for understanding how the gut and brain may be communicating and how microbial metabolites may be acting as crucial messengers. Our focus here is to synthesize the evidence showing how these metabolites directly trigger the inflammatory processes seen in AD. The gut microbiome in AD is often dysbiotic, leading to an unhealthy balance of microbial byproducts. Pro-inflammatory molecules such as lipopolysaccharide and trimethylamine N-oxide increase, while beneficial ones may decrease. These compounds can compromise the blood–brain barrier and gain access to the brain where they activate glial cells. The chronic neuroinflammation central to AD pathology might be driven by this continuous activation of microglia and astrocytes. Targeting this gut-brain connection may offer a novel therapeutic strategy where modulating the microbiome could potentially disrupt this inflammatory cascade.
Prajapati et al. (Tue,) studied this question.