Alzheimer’s disease is the most common cause of
dementia. Still incurable, it directly affects nearly one 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,
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, confirm the correlation, in
humans, between an imbalance in the gut microbiota and the development of
amyloid plaques in the brain, which are at the origin of the neurodegenerative
disorders characteristic of Alzheimer’s disease.
Proteins produced by certain
intestinal bacteria, identified in the blood of patients, could indeed modify
the interaction between the immune and the nervous systems and trigger the
disease.
These results, to be
discovered in the Journal of Alzheimer’s Disease,
make it possible to envisage 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 Centre and professor
at the Department of Rehabilitation and Geriatrics of the UNIGE Faculty of
Medicine, has been working for several years now on the potential influence of
the gut microbiota on the brain, and more particularly on neurodegenerative
diseases. “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,” he explains.
“Their microbiota has indeed
a reduced microbial diversity, 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?”
The
brain under influence
Intestinal bacteria can
influence the functioning of the brain and promote 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 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 some
short-chain fatty acids – which, having neuroprotective and anti-inflammatory
properties, directly or indirectly affect brain function.
“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 suffered from
Alzheimer’s disease or other neurodegenerative diseases causing similar memory
problems, while others did not have any memory problems,” reports Moira
Marizzoni, a 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 inflammation markers 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 quantity 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 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 a blood inflammatory phenomenon. Scientists will now work
to identify specific bacteria, or a group of bacteria, involved in this
phenomenon.
A
strategy based on prevention
This discovery paves the way
for potentially highly innovative protective strategies – through the
administration of a bacterial cocktail, for example, or of pre-biotics to feed
the ‘good’ bacteria in our intestine. “However, we shouldn’t be too quick to
rejoice,” says Frisoni.
“Indeed, we must first
identify the strains of the cocktail. Then, a neuroprotective effect could only
be effective at a very early stage of the disease, with a view to prevention
rather than therapy. However, early diagnosis is still 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
appearance of detectable symptoms.”
This study is also part of a
broader prevention effort led by the UNIGE Faculty of Medicine and the HUG
Memory Centre.
Journal article(under
paywall): https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200306
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