The link between Alzheimer’s disease and the gut microbiota is confirmed

Alzheimer’s disease is the most common cause of dementia. Still incurable, it directly affects nearly a million people in Europe, and indirectly millions of family members as well as society as a whole. In recent years, the scientific community has suspected that the gut microbiota plays a role in the development of the disease.

A team from the University of Geneva (UNIGE) and the University Hospitals of Geneva (HUG) in Switzerland, as well as Italian colleagues from the National Center for Research and Care for Alzheimer’s Disease and Fatebenefratelli in Brescia, the University of Naples and the IRCCS SDN Research Center of Naples, confirm the correlation, in humans, between an imbalance of the intestinal microbiota and the development of amyloid plaques in the brain, which are the cause of characteristic neurodegenerative disorders of Alzheimer’s disease. The proteins produced by certain intestinal bacteria, identified in the blood of patients, could indeed modify the interaction between the immune system and the nervous system and trigger the disease. These results, published in the Alzheimer’s Disease Journal, allow to consider new preventive strategies based on the modulation of the microbiota of people at risk.

The research laboratory of neurologist Giovanni Frisoni, director of the HUG Memory Center and professor in the Rehabilitation and Geriatrics Department of the UNIGE Faculty of Medicine, has been working for several years now on the potential influence of the intestinal microbiota on the brain, and more particularly on neurodegenerative diseases. “We have already shown that the composition of the gut microbiota in patients with Alzheimer’s disease is altered compared to people who do not suffer from such disorders,” he explains. “Their microbiota has indeed reduced microbial diversity, with an overrepresentation of certain bacteria and a sharp decrease in other microbes. In addition, 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 the inflammation of the blood be a mediator between the microbiota and the brain? “

The brain under influence

Intestinal bacteria can influence the functioning of the brain and promote neurodegeneration through several pathways: they can influence the regulation of the immune system and, consequently, modify the interaction between the immune system and the nervous system. Lipopolysaccharides, a protein located on the membrane of bacteria with pro-inflammatory properties, have been found in amyloid plaques and around vessels in the brains of people with Alzheimer’s disease. In addition, the intestinal microbiota produces metabolites – in particular certain short-chain fatty acids – which, having neuroprotective and anti-inflammatory properties, directly or indirectly affect the functioning of the brain.

“To determine whether inflammation mediators and bacterial metabolites link the gut microbiota to amyloid pathology in Alzheimer’s disease, we studied a cohort of 89 people aged 65 to 85. Some suffered from Alzheimer’s disease or other neurodegenerative diseases causing similar memory. problems, while others had no memory problems, ”reports Moira Marizzoni, researcher at the Fatebenefratelli Center in Brescia and first author of this work. “Using PET imaging, we measured their amyloid deposition and then quantified the presence in their blood of various markers of inflammation and proteins produced by intestinal bacteria, such as lipopolysaccharides and short-chain fatty acids.”

A very clear correlation

“Our results are indisputable: certain bacterial products of the intestinal microbiota are correlated with the amount of amyloid plaques in the brain,” explains Moira Marizzoni. “Indeed, high blood levels of lipopolysaccharides and certain short chain fatty acids (acetate and valerate) were associated with the two 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 intestinal microbiota and cerebral amyloidosis through an inflammatory phenomenon in the blood. Scientists will now work to identify specific bacteria, or a group of bacteria, involved in this phenomenon.

A strategy based on prevention

This discovery opens the way for potentially very innovative protection strategies – via the administration of a bacterial cocktail, for example, or pre-biotics to nourish the “good” bacteria in our intestines. “However, we shouldn’t be celebrating too quickly,” says Frisoni. “Indeed, we must first identify the strains of the cocktail. Next, a neuroprotective effect could only be effective at a very early stage of the disease, from a prevention rather than a therapeutic perspective. However, early diagnosis remains one of the main challenges in the management of neurodegenerative diseases, as protocols must be developed to identify high risk individuals and treat them well before the onset of detectable symptoms. ”