It is widely assumed that gut microbeta plays a vital role in developing Alzheimer’s disease in recent years. Now, a team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) in Switzerland, together with Italian colleagues from the National Research and Care Center for Alzheimer’s and Psychiatric Diseases Fatebenefratelli in Brescia, University of Naples, and the IRCCS SDN Research Center in Naples, confirmed the correlation, between Alzheimer’s disease and gut microbiota.
Their study, published in the Journal of Alzheimer’s Disease, suggests that an imbalance in the gut microbiota and the development of amyloid plaques in the brain leads to the neurodegenerative disorders characteristic of Alzheimer’s disease. Proteins produced by certain intestinal bacteria, identified in patients’ blood, could modify the interaction between the immune and the nervous systems and trigger the disease.
The research laboratory of neurologist Giovanni Frisoni, director of the HUG Memory Centre and professor at the Department of Rehabilitation and Geriatrics of the UNIGE Faculty of Medicine said, “We have already shown that the gut microbiota composition in patients with Alzheimer’s disease was altered, compared to people who do not suffer from such disorders.”
“Their microbiota has a reduced microbial diversity indeed, with an over-representation of certain bacteria and a strong decrease in other microbes. Furthermore, we have also discovered an association between an inflammatory phenomenon detected in the blood, certain intestinal bacteria, and Alzheimer’s disease; hence the hypothesis that we wanted to test here: could inflammation in the blood be a mediator between the microbiota and the brain?”
Intestinal bacteria have a significant impact on brain’s function. It can lead to neurodegeneration through several pathways: they can indeed influence the regulation of the immune system and, consequently, can modify the interaction between the immune system and the nervous system.
Lipopolysaccharides, a protein situated on the membrane of bacteria with pro-inflammatory properties, have been found in amyloid plaques and around vessels in the brains of individuals with Alzheimer’s. Moreover, the intestinal microbiota produces metabolites – specifically some short-chain fatty acids – which, having neuroprotective and anti-inflammatory properties, directly or indirectly affect brain function.
Moira Marizzoni, a researcher at the Fatebenefratelli Center in Brescia and first author of this work, said, “To determine whether inflammation mediators and bacterial metabolites constitute a link between the gut microbiota and amyloid pathology in Alzheimer’s disease, we studied a cohort of 89 people between 65 and 85 years of age. Some had Alzheimer’s disease or other neurodegenerative diseases causing similar memory problems, while others did not have any memory problems. Using PET imaging, we measured their amyloid deposition. We then quantified the presence in their blood of various inflammation markers and proteins produced by intestinal bacteria, such as lipopolysaccharides and short-chain fatty acids.”
“Our results are indisputable: certain bacterial products of the intestinal microbiota are correlated with the number of amyloid plaques in the brain. Indeed, high blood levels of lipopolysaccharides and certain short-chain fatty acids (acetate and valerate) were associated with both large amyloid deposits in the brain. Conversely, high levels of another short-chain fatty acid, butyrate, were associated with less amyloid pathology.”
“This work thus provides proof of an association between certain proteins of the gut microbiota and cerebral amyloidosis through an inflammatory blood phenomenon.”
In future studies, scientists will identify specific bacteria, or a group of bacteria, involved in this phenomenon.
- Marizzoni, Moira, et al. ‘Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease.’ 1 Jan., 2020: 683 – 697. DOI: 10.3233/JAD-200306