Scientists have discovered a connection between the development of Alzheimer's disease and the bacteria in the body's digestive system.
Using artificial intelligence, researchers at the Cleveland Clinic Genome Center in Ohio identified how metabolites produced by gut bacteria may interact with brain cell receptors, contributing to the disease. The findings could eventually lead to the development of new therapeutic interventions or drugs to prevent Alzheimer's disease, a condition that affects nearly 7 million Americans.
Alzheimer's disease is a progressive neurodegenerative condition that primarily affects older adults. It leads to the decline of cognitive functions such as memory, emotional regulation and reasoning. Although there is no cure, medications can slow the progression of the disease.
For the study, the team used a type of AI called machine learning to analyze more than 1.09 million potential interactions between bacterial byproducts called metabolites and cell receptors.
Bacteria release metabolites into our systems as they break down the food we eat for energy. The metabolites then interact with and influence our cells, fueling cellular processes that can be helpful or detrimental to health.
The researchers ranked metabolites and receptors by the likelihood they will interact with each other. They also examined which metabolite-receptor pairs were likely to influence Alzheimer's disease in brain cells derived from patients with the condition.
The researchers discovered that one metabolite called agmatine may help to protect brain cells from inflammation and the subsequent damage. Specifically, they found agmatine was most likely to interact with a brain cell receptor called CA3R in Alzheimer's disease.
When the researchers treated Alzheimer's-affected neurons with agmatine, it directly reduced CA3R levels, which suggests that the metabolite and receptor influence each other.
Neurons treated with agmatine also had lower levels of phosphorylated tau proteins, a marker for Alzheimer's disease.
Preventing harmful interactions between metabolites and our cells could help fight disease. However, research into this approach takes a long time because of the huge amounts of information necessary to identify a target receptor. Using AI helped to speed up the process.
"Gut metabolites are the key to many physiological processes in our bodies, and for every key there is a lock for human health and disease," said study researcher Feixiong Cheng in a press statement.
"The problem is that we have tens of thousands of receptors and thousands of metabolites in our system, so manually figuring out which key goes into which lock has been slow and costly."
The full findings of the study were published in Cell Reports.
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