While the other projects in the Microbiome consortium focus on how gut microbes affect Alzheimer’s disease (AD), this study focuses on the brain microbiome. The concept of a brain microbiome has been debated for years, because the brain has specialized immune barriers that should prevent microbes from entering. However, there is growing evidence that the brain is not as sterile as previously thought, particularly under weakened or diseased conditions.
Brain infections may contribute to AD by triggering inflammation. Interestingly, research from Dr. Tanzi’s lab suggests that amyloid beta has antimicrobial properties, meaning it can form a barrier around potentially harmful pathogens in the brain and prevent their spread. These amyloid “seeds” may then lead to larger amyloid deposits that build up into the plaques that characterize the AD brain.
During the first Microbiome consortium cycle, Drs. Tanzi and Shanmugam found a surprisingly high number of gut bacteria in brain tissue from AD and control patients. The types of bacteria found in brain areas with amyloid plaques differed from those without. To further compare changes in the gut microbiome with those observed in the brain, they began collecting human fecal samples from AD patients. This ambitious, time-intensive effort will continue in the next cycle.
Additionally, Drs. Tanzi and Shanmugam plan to isolate extracellular vesicles, tiny cargo-carrying bubbles from patient fecal samples, to determine if they drive the inflammatory changes caused by the gut microbiome. They will also expand their study to include an identification of bacterial species adjacent to tau pathology. Finally, they will test whether a synbiotic approach in AD mouse models improves disease outcomes. Synbiotics consist of prebiotics, non-digestible fibers that promote bacterial growth, and probiotics containing beneficial bacteria and microbiota. The combination of the two enhances the benefits typically seen with either a pre- or probiotic alone.
