Fight Aging!

A growing body of evidence points to an altered gut microbiome in Alzheimer's patients. If only a specific subset of the varied age-related changes observed to take place in the gut microbiome across the broader population provide a significant contribution to the early pathology of the condition, this may help to explain why many older people fail to develop Alzheimer's disease despite exhibiting all of the other known risk factors. Are gut microbiome characteristics that appear in Alzheimer's patients a contributing cause of the condition, or do they stem from, perhaps, greater immune dysfunction with age, and that immune dysfunction is the important factor? That has yet to be determined, but since the aging gut microbiome can be rejuvenated by fecal microbiota transplant from young individuals, it seems that whether or not the gut microbiome contributes to Alzheimer's disease could be determined given the will and funding to run a clinical trial.

Alzheimer's disease (AD) pathology is thought to progress from normal cognition through preclinical disease and ultimately to symptomatic AD with cognitive impairment. Recent work suggests that the gut microbiome of symptomatic patients with AD has an altered taxonomic composition compared with that of healthy, cognitively normal control individuals. However, knowledge about changes in the gut microbiome before the onset of symptomatic AD is limited.

In this cross-sectional study that accounted for clinical covariates and dietary intake, we compared the taxonomic composition and gut microbial function in a cohort of 164 cognitively normal individuals, 49 of whom showed biomarker evidence of early preclinical AD. Gut microbial taxonomic profiles of individuals with preclinical AD were distinct from those of individuals without evidence of preclinical AD. The change in gut microbiome composition correlated with β-amyloid (Aβ) and tau pathological biomarkers but not with biomarkers of neurodegeneration, suggesting that the gut microbiome may change early in the disease process.

We identified specific gut bacterial taxa associated with preclinical AD. Inclusion of these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status when tested on a subset of the cohort (65 of the 164 participants). Gut microbiome correlates of preclinical AD neuropathology may improve our understanding of AD etiology and may help to identify gut-derived markers of AD risk.

Link: https://doi.org/10.1126/scitranslmed.abo2984