Alzheimer's Disease: Could the Gut Microbiome be a Causative Factor?

Thursday - October 26 2023, 22:42 UTC - 1 year ago

Recent research has suggested that alterations in the gut microbiome composition of Alzheimer's patients could be causal in the manifestation of Alzheimer's symptoms. We transplanted the microbial communities of Alzheimer's patients and age-matched healthy controls into microbiota-depleted rats and found impairments in memory behaviors, particularly those that rely on a process called adult hippocampal neurogenesis, and decreases in neurogenesis in human cells in vitro. This confirms a causal role of gut microbiota in the development of Alzheimer's disease.

Alzheimer’s disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer’s disease by showing specific alterations in the gut microbiome composition of Alzheimer’s patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer’s symptoms.

To understand the involvement of Alzheimer’s patient gut microbiota in host physiology and behavior, we transplanted faecal microbiota from Alzheimer’s patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer’s patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer’s systemic environment on proxy neurogenesis readouts. Serum from Alzheimer’s patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera.

Our findings reveal for the first time, that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer’s disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer’s. These findings have the potential to open up novel therapeutic strategies for supplementation and treatment of Alzheimer’s disease and pave the way for further exploration of the unique role gut-brain interactions play in the development of Alzheimer’s as well as other neurological disorders.