腸内細菌の変化はアルツハイマー病の初期症状である可能性がある(Altered gut bacteria may be early sign of Alzheimer’s disease)

2023-06-14 ワシントン大学セントルイス校

<関連情報>

• https://source.wustl.edu/2023/06/altered-gut-bacteria-may-be-early-sign-of-alzheimers-disease/
• https://www.science.org/doi/10.1126/scitranslmed.abo2984

腸内細菌叢の構成が前臨床アルツハイマー病の指標となる可能性 Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease

Aura L. Ferreiro,JooHee Choi,Jian Ryou,Erin P. Newcomer,Regina Thompson,Rebecca M. Bollinger,Carla Hall-Moore,I. Malick Ndao,Laurie Sax,Tammie L. S. Benzinger,Susan L. Stark,David M. Holtzman,Anne M. Fagan,Suzanne E. Schindler,Carlos Cruchaga,Omar H. Butt,John C. Morris,Phillip I. Tarr,Beau M. Ances,and Gautam Dantas
Science Translational Medicine  Published:14 Jun 2023
DOI:https://doi.org/10.1126/scitranslmed.abo2984

Abstract

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.

Editor’s summary

Individuals with Alzheimer’s disease (AD) may have an altered gut microbiome, and these changes may occur early in the disease course. Now, Ferreiro et al. show that the gut microbiomes of people with preclinical AD (indicated by altered brain amyloid and tau proteins) had a different composition from that of healthy individuals. Gut microbial taxa correlated with amyloid and tau markers of preclinical AD, but not with signatures of neurodegeneration. Specific gut bacteria were identified as being associated with preclinical AD, and their inclusion improved machine learning predictions of preclinical AD status. —Orla Smith