Recent research has suggested that the gut microbiome may play a role in Alzheimer’s disease, and researchers from Ohio propose that targeting this axis could be a potential treatment approach. They used machine learning tools to predict which metabolites, by-products of bacteria in the gut, could influence Alzheimer’s disease by binding with specific receptors in the gut and brain. By evaluating over 1 million potential pairs of metabolites and receptors, they were able to identify which ones might bind together and affect biological pathways related to Alzheimer’s disease.
The gut metabolites are indicative of the bacteria present in the gut, and changes in the gut microbiome have been linked to Alzheimer’s disease. This research aims to shed light on the role of the microbiome in Alzheimer’s by identifying key metabolites that bind with specific receptors. The gut-brain axis is thought to influence brain health due to its role in immune function, and researchers believe that the communication between the gut and the brain may impact cognitive decline seen in Alzheimer’s. By targeting the brain-gut axis, researchers hope to develop new treatment strategies for Alzheimer’s disease that do not require direct delivery to the brain.
The findings from this study suggest that preventing potentially harmful binding of metabolites to receptors could help reduce the risk of Alzheimer’s disease. By analyzing relationships between receptors and Alzheimer’s disease, researchers were able to predict which metabolites would bind to these receptors, most of which were lipid-like metabolites. They also identified two metabolites, agmatine and phenethylamine, which are produced by specific bacteria abundant in the gut microbiome of individuals with Alzheimer’s disease. These metabolites were found to have a significant impact on reducing tau levels, a protein associated with Alzheimer’s disease development.
Researchers conducted experiments on forebrain neurons derived from induced pluripotent stem cells of individuals with Alzheimer’s disease to observe the effects of agmatine and phenethylamine on tau levels. They found that both metabolites significantly reduced levels of tau in a dose-dependent manner, which is a promising development in potential Alzheimer’s disease treatment. Further preclinical studies are planned to test the efficacy of these gut metabolites in preventing or treating Alzheimer’s disease. The researchers believe that by improving gut health, tau levels in the brain may be influenced, leading to potential therapeutic benefits for Alzheimer’s disease.
Given the high rate of failure in clinical trials for Alzheimer’s disease treatments, this research points to a new target for potential intervention. By understanding the role of the gut-brain axis in Alzheimer’s disease, researchers hope to pave the way for novel treatment approaches that may be more effective than current strategies. The open science approach adopted by the researchers allows for the sharing of their findings with the scientific community, enabling other researchers to build upon this research and contribute to the fight against the Alzheimer’s disease crisis. Further investigations into the impact of gut metabolites on tau levels in animal and human samples are ongoing to better understand the potential of targeting the brain-gut axis for Alzheimer’s disease treatment.
