Microbiome changes may help make a diagnosis of preclinical Alzheimer’s disease

Last March on this blogsite, I described evidence that chronic laxative use can increase the risk of getting dementia. The  cause of this increased risk was thought to involve disruption of the gut microbiome, the millions of microorganisms that live in our gut.  These include bacteria, viruses, fungi, yeasts, and bacteriophages that begin to colonize the gut at birth, and reach a stable population at about age three. While it has been previously reported that modulation of the gut microbiome can slow progression of dementia in a mouse model of Alzheimer’s, there is little information of the status of the gut microbiome in human Alzheimer’s disease, especially in the preclinical stages, before the onset of cognitive impairment

Now in a paper published last week in Science Translational Medicine, the researchers reported a shift in the gut microbiome composition correlated with beta-amyloid and tau pathological biomarkers but not with biomarkers of neurodegeneration. This suggests that the gut microbiome may change early in the disease process before brain volume loss has started. They identified specific gut micro-organisms associated with preclinical Alzheimer’s disease. These micro-organisms included Dorea formicigenerans, Oscillibacter sp, Faecalibacterium prausnitzii, Coprococcus catus, and Anaerostipes hadrus.  Inclusion of these microbiome features improved the accuracy, sensitivity, and specificity of machine learning classifiers for predicting preclinical AD status. Gut microbiome predictors of preclinical AD neuropathology may improve our understanding of AD etiology and may help to identify gut-derived markers for Alzheimer’s. The authors concluded: “we report global and specific differences in the gut microbiome at the preclinical stage of AD. We further demonstrate that addition of gut microbiome features improved accuracy, sensitivity, and specificity of classifiers for preclinical AD. Microbiome markers in stool might complement early screening measures for preclinical AD and generate encouraging hypotheses about potential roles of the gut in AD progression. Last, microbially at-risk populations could open new opportunities for gut-directed interventions to interdict progression to clinical AD.”