Facilitating role of the intestinal microbiota in the development of Alzheimer’s disease

Vignette

Intestinal dysbioses seem to be involved in the pathophysiological mechanisms of Alzheimer’s disease and to increase the cognitive deficit.

 

Studies suggest a connection between the intestinal microbiota and Alzheimer’s disease. Chinese researchers compared the intestinal microbiota and the intestinal microarchitecture over time in wild type mice and mouse models of Alzheimer's disease. For the 2 groups, they collected fecal samples at the ages of 1, 3, 5-6, and 8-12 months and studied the diversity and volume of bacteria, as well as the impact of the composition of the intestinal microbiota on signaling pathways.

The composition of the microbiota changes as all animals grow older. However, differences were observed between the two groups of mice. The “Alzheimer’s” mice had an excess of Proteobacteria at the age of 5-6 months, and an excess of Verrucomicrobia and a deficit of Ruminococcus and Butyricicoccus pullicaecorum at the age of 8-12 months. These dysbioses are associated with a disorder in around thirty signaling and/or metabolic pathways, in particular the butyrate metabolic pathway, a short-chain fatty acid (SCFA) with a probiotic effect that protects neurons against inflammatory processes. This phenomenon, associated with a reduction in butyrate-producing B. pullicaecorum, prompted the authors to measure the levels of SCFA in the study mice. The “Alzheimer’s” mice had a deficit of SCFA, with low levels in the brain correlated with those found in the feces.

The authors also observed amyloid deposits in the intestines of the “Alzheimer’s” mice, starting at the age of five months, as well as structural anomalies such as filaments identical to senile plaques in the brain, shorter and irregular villi, and mitochondrial degeneration.

According to the authors, these deposits and structural changes could potentially promote intestinal dysbiosis, and, as a result, contribute to the SCFA deficit and increase the cognitive symptoms of the disease.

 

Sources:

Zhang L et al. Altered Gut Microbiota in a Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2017;60 :1241–1257.