Gut Microbiota Changes and Their Correlation with Cognitive and Neuropsychiatric Symptoms in Alzheimer’s Disease

Gut microbiota can influence human brain function and behavior. Recent studies showed that gut microbiota might play an important role in the pathogenesis of Alzheimer's disease (AD).To investigate the composition of gut microbiota in AD patients and their association with cognitive function and neuropsychiatric symptoms (NPS).The fecal samples from 60 AD patients (30 with NPS and 30 without NPS) and 32 healthy control subjects (HC) were collected and analyzed by 16S ribosomal RNA sequencing. The functional variations of gut microbiota were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. The correlation between different bacterial taxa and cognitive (Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)), and NPS measures were analyzed.The fecal microbial composition of AD patients was quite distinct from HC. Bifidobacterium, Sphingomonas, Lactobacillus, and Blautia were enriched, while Odoribacter, Anaerobacterium, and Papillibacter were reduced. AD patients with NPS showed decreased Chitinophagaceae, Taibaiella, and Anaerobacterium compared with those without NPS. Functional pathways were different between AD and HC, and between AD patients with and without NPS. Correlation analysis showed that Sphingomonas correlated negatively with MMSE; Anaerobacterium and Papillibacter correlated positively with MMSE and negatively with CDR. Cytophagia, Rhodospirillaceae, and Cellvibrio correlated positively with NPS, while Chitinophagaceae, Taibaiella, and Anaerobacterium correlated negatively with NPS.AD patients have gut microbiota alterations related to cognition, and differential taxa between AD patients with and without NPS associated differently with NPS domains, which helps further understand the pathogenesis of AD and explore potential therapeutic targets.