Study offers “indisputable” link between Alzheimer’s and gut microbiome

2020-11-15

Research into the relationship between the brain and the bacteria in our bellies is uncovering links to an increasing number of neurological conditions, with Alzheimer’s among them. A new study is throwing further weight behind the theory that an imbalance in the gut microbiome may be related to the onset of the disease, showing how shifts in bacterial diversity are associated with inflammation and heightened numbers of amyloid plaques in the brain, one of the hallmarks of the condition.

The community of bacteria that lives in our gut has become the focus of much medical research of late, with scientists uncovering evidence that it can play a role in depression, autism, multiple sclerosis and heart disease, to name just a few examples. Likewise, connections have begun to emerge between the gut microbiome and Alzheimer’s disease, with one 2017 study revealing decreases in microbiome diversity among those diagnosed with the condition.

Last year, Chinese authorities even approved a novel drug designed to treat the disease by modulating a person’s gut microbiome that became the first Alzheimer’s drug to reach the market in almost 20 years. Another recent study found that fecal transplants in mice can affect age-related cognitive decline by altering the gut micriobome.

The international team of scientists behind the new study claim that it has confirmed this correlation. Study author Giovanni Frisoni from the University Hospitals of Geneva has been investigating these links for several years and previously uncovered evidence of reduced microbiome diversity among Alzheimer’s patients, and suspects that one of the flow-on effects of this, inflammation, may also have an important part to play.

“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?” says Frisoni.

In search of answers to this question, the researchers used PET imaging to measure amyloid plaque buildup and inflammation markers in the blood of a cohort of 89 people, all between the ages of 65 and 85 and some with Alzheimer’s or related conditions and some without.

The team was on the lookout for a couple of markers in particular. Lipopolysaccharides are endotoxins found in the membrane of pro-inflammatory bacteria and have also been spotted in amyloid plaques and vessels in the brains of Alzheimer’s sufferers. Some short-chain fatty acids produced by the gut microbiota, meanwhile, can have a protective anti-inflammatory effect.

“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 first author of the study. “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.”

While the scientists describe this as proof of the correlation between an altered composition of gut bacteria and the amyloid plaques associated with Alzheimer’s, understanding whether it contributes to the disease or is simply a consequence of it is the great unknown. Nonetheless, the more we understand these relationships the more we can uncover potential new pathways for treatment, with the authors of the new study already floating some ideas, such as a bacterial cocktail that boosts “good” bacteria numbers.

“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.”

The research was published in the Journal of Alzheimer’s Disease.

newatlas.com, 15 November 2020
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