Gut microbiome alterations in preclinical Alzheimer's disease

Background Although some human studies have reported gut microbiome changes in individuals with Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI), gut microbiome alterations in preclinical AD, i.e., cerebral amyloidosis without cognitive impairment, is largely unknown. Objective We aimed to identify gut microbial alterations associated with preclinical AD by comparing cognitively normal (CN) older adults with cerebral A beta deposition (A beta+ CN) and those without cerebral A beta deposition (A beta- CN). Methods Seventy-eight CN older participants (18 A beta+ CN and 60 A beta- CN) were included, and all participants underwent clinical assessment and Pittsburg compound B-positron emission tomography. The V3-V4 region of the 16S rRNA gene of genomic DNA extracted from feces was amplified and sequenced to establish the microbial community. Results Generalized linear model analysis revealed that the genera Megamonas (B = 3.399, q<0.001), Serratia (B = 3.044, q = 0.005), Leptotrichia (B = 5.862, q = 0.024) and Clostridium (family Clostridiaceae) (B = 0.788, q = 0.034) were more abundant in the A beta+ CN group than the A beta- CN group. In contrast, genera CF231 (B = -3.237, q< 0.001), Victivallis (B = -3.447, q = 0.004) Enterococcus (B = -2.044, q = 0.042), Mitsuokella (B = -2.119, q = 0.042) and Clostridium (family Erysipelotrichaceae) (B = -2.222, q = 0.043) were decreased in A beta+ CN compared to A beta- CN. Notably, the classification model including the differently abundant genera could effectively distinguish A beta+ CN from A beta- CN (AUC = 0.823). Conclusion Our findings suggest that specific alterations of gut bacterial taxa are related to preclinical AD, which means these changes may precede cognitive decline. Therefore, examining changes in the microbiome may be helpful in preclinical AD screening.

Automated summary

This study found specific alterations of gut bacterial taxa associated with preclinical Alzheimer's disease, suggesting that these changes may occur before cognitive decline.