Alzheimer’s: the risk lies along the gut-brain axis – here’s what the microbiota conceals

The Gut-Brain Axis. Or, if you prefer, the gut-brain axis. The more research progresses, the more we discover that the interactions between the inhabitants of the ‘megacity’ that is our digestive system and the wellbeing of the central nervous system are closely and firmly interlinked. In fact, the gut microbiota could even act as a sort of ‘production centre’ for molecules that may, in some way, have a negative impact on the risk of developing Alzheimer’s disease and, more generally, vascular problems that can lead to cognitive decline. In this regard, confirmation has now emerged, almost a decade after the discovery that the composition of the gut bacterial population differs in people with Alzheimer’s disease compared with healthy individuals.

Under the microscope is a substance, imidazole propionate (ImP), produced by intestinal bacterial strains. A study published in Nature Communications (first author Vaibavh Vemuganti) and led by Barbara Bendlin and Federico Rey of the University of Wisconsin-Madison (the same researchers who had previously noted differences in the composition of gut microbiota in the presence of neurological disease) suggests that ImP may in some way contribute to the brain changes typical of conditions characterised by cognitive decline and could even become a potential therapeutic target in the future. Researchers from the University of California, Los Angeles and the University of Gothenburg also took part in the study.

ImP production varies considerably from person to person. Some individuals appear to produce relatively high levels of it, whilst others produce very little. “Bacteria that produce ImP are present in a high proportion of people, but they are not very abundant in most cases,” notes Rey in a statement from the American university. “However, we have learnt over the years that a microbe does not necessarily need to be abundant to have an impact on the host.” Once produced in the gut, ImP can enter the bloodstream. The study suggests that the compound’s effects could extend to the brain, influencing the well-being of neurons. In experimental animals, in fact, ImP promotes an increase in the accumulation of abnormal beta-amyloid and tau proteins – two hallmarks of neurological disease – which lead to the death of nerve cells.

As if that were not enough, an analysis of blood samples from just under 1,200 people enrolled in the Wisconsin Alzheimer’s Prevention Registry, as well as data emerging from studies conducted by the Wisconsin Alzheimer’s Disease Research Centre, has shown that those with higher concentrations of ImP in their blood were far more likely to exhibit biological markers associated with abnormal proteins and impaired neuronal function in the the course of cognitive decline. Furthermore, by analysing repeated cognitive tests carried out over time on these volunteers, it was possible to compare ImP levels with changes in thinking skills and memory. The result, as Rey notes: “People with the highest levels of ImP also experienced a much more rapid cognitive decline.” One final point of interest: the researchers also identified a genetic variant associated with substantially higher levels of ImP in the blood, with around 43 per cent of the study participants carrying this genetic variant.

The suspicion is that a genetic predisposition may influence the effectiveness of the kidneys’ ability to clear ImP from the blood, thereby affecting the amount of the compound that remains in circulation. “This genetic variant has already been linked to an increased risk of Alzheimer’s in large-scale genetic studies, and now we may understand why,” concludes Rey. “These findings reaffirm the importance of so-called personalised medicine,” comments Donato Angelino, lecturer in Food and Human Nutrition at the University of Teramo. In other words, they lead us once again to consider the individual as a unique entity with specific characteristics – such as particular gut microbial strains and/or their metabolites and health conditions – which influence disease risk and, consequently, to tailor the appropriate treatment. All this is also thanks to the omics sciences, such as metabolomics and proteomics, which detect specific molecules and, using complex algorithms, link them together to provide a complete picture of their effects.”