Research into the effects of the human microbiome on health and aging has progressed quite rapidly in recent years. It now costs little to sequence a sample to determine the which bacterial species are present and in what proportions. With age, the intestinal barrier, blood vessels, and blood-brain barrier begin to leak, allowing greater passage of microbes into the body. Additionally, the immune system declines in function, reducing the ability to clear these microbes from tissues.
In the case of patients with Alzheimer's disease, researchers are finding that the gut microbiome exhibits characteristic differences when compared with old people without this condition. The work here shows that this difference extends to the microbes leaking into the brain. This may indicate that specific immune dysfunction is present in Alzheimer's disease, favoring certain microbial species, or more likely, that changes in the microbiome provide an important contribution to the onset and progression of this form of dementia. The precise details as to why this is the case, over and above merely considering increased inflammation, remain to be determined.
When biomes turn unhealthy, either by invasion of outside pathogens, or a major change in the relative numbers of the microbial species present, a dysbiosis, or imbalance in the microbiota, occurs. This dysbiosis can alter human metabolism and cause inflammation, which has been linked to the tissue damage seen in ulcerative colitis, rheumatoid arthritis, and many other chronic inflammatory diseases. Studying 130 samples from the donated brains of 32 people - 16 with Alzheimer's and 16 age-matched controls without the disease, researchers found bacterial flora in all the brains- but the Alzheimer's brains showed profoundly different bacterial profiles compared to their age-matched controls.
The group used full-length 16s ribosomal RNA gene sequencing, a technique that can detect any and all bacterial species present in a sample. In this process, the researchers pinpointed disease-specific sets of bacteria in almost all of the Alzheimer's-affected brains, suggesting these groups of bacteria are strong predictors of the disease. The authors detected five brain microbiomes, four that are hypothesized to be present at different times in the evolution of the Alzheimer's-afflicted brains. The authors said it is likely that the observed Alzheimer's microbiomes evolve to become more pathogenic as the disease progresses with the later stages characterized as a pathobiome. The authors hypothesize that the brain begins with a healthy biome, but as the disease develops, the healthy biome is supplanted as a new set of microbes replace the original healthy ones with the eventual emergence of the Alzheimer's pathobiome.
Samples from both sets of brain samples were drawn from the frontal and temporal lobes and entorhinal cortex. Based on the random distribution of microbiomes requiring delivery all over the brain, the results were consistent with failure in one or more of the brain's networks; however it too soon to tell if the observed distribution patterns result from a leaky blood-brain barrier, the brain's glymphatic system, or synaptonemal transmission that allowed bacteria, including Cutibacterium acnes (formerly called Proprionibacterium acnes), Methylobacterium, Bacillus, Caulobacter, Delftia, and Variovora to enter the brain. In Alzheimer's brain samples, the researchers noted, these pathogenic bacteria appeared to have overpowered and replaced Comamonas sp. bacteria, which are associated with a dementia-free brain.