Alzheimer's Disease Alters the Gastrointestinal Immunity in Mice

In a groundbreaking study published in Cell Reports, researchers at the Buck Institute have shed light on the potential role of the gut-brain axis in Alzheimer's disease. Led by Dr. Dina Jacobs and her team, the study focuses on the colon of the Alzheimer's 5XFAD amyloid-β mouse model.

The research reveals that in the context of Alzheimer's disease, specific bacteria might set off immune system inflammation. Age-related insults could trigger Alzheimer's disease-causing inflammation in the brain, with chemokines signaling the gut immune system for help in dealing with the insult.

Remarkably, immune cells in the brain border that recognise bacteria living in the intestines were found to be accumulating in the Alzheimer's disease brain. One such cell type is the CXCR4+ antibody-secreting cell, which corresponds with accumulating CXCR4+ B cells and gut-specific IgA+ cells in the brain and dura mater, respectively.

The team found several Alzheimer's-associated changes in B cell (plasma cells, specifically) activity in the colon immune compartment of the 5XFAD mice. Levels of CXCR4+ antibody-secreting cells were reduced in these mice's colons.

To explore potential therapeutic avenues, the researchers investigated the effects of a high-fiber diet. The anti-inflammatory pre-biotic fiber inulin restored balance in the gut of the mice, expanding gut IgA+ cells, rescuing peripheral Treg levels, reducing dysbiosis, improving serum microbial metabolite levels, and attenuating overall Alzheimer's-associated frailty, including tremor.

While the high fiber diet did not consistently reduce the levels of plaques in the mice's brain, it did impact overall well-being. The team suggests that feeding the mice a high fiber diet could "reduce chemokine signaling in the brain."

Dr. Jacobs and her team are eager to explore the potential of understanding and/or altering the gut microbiome in the context of disease. One intriguing idea is inhibiting signaling chemokines early versus late in the disease process as a protective measure. The paper suggests many avenues for further exploration, particularly in understanding and manipulating the gut microbiome in relation to Alzheimer's disease.

In conclusion, this study provides valuable insights into the role of the gut-brain axis in Alzheimer's disease and the potential benefits of a high-fiber diet in alleviating Alzheimer's-related frailty. As research continues, the gut microbiome may hold the key to new treatments and therapies for Alzheimer's disease.