Abstract
BackgroundGut microbiota (GMB) alteration has been reported to influence the Alzheimer’s disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. This study aims to investigate metabolic output of the dysbiosis of GMB in AD pathogenesis. In this study, the fecal microbiota and metabolome from 21 AD participants and 44 cognitively normal control participants were measured. Untargeted GMB taxa was analyzed through 16S ribosomal RNA gene profiling based on next-generation sequencing and fecal metabolites were quantified by using ultrahigh performance liquid chromatography-mass spectrometry (UPLC-MS).ResultsOur analysis revealed that AD was characterized by 15 altered gut bacterial genera, of which 46.7% (7/15 general) was significantly associated with a series of metabolite markers. The predicted metabolic profile of altered gut microbial composition included steroid hormone biosynthesis, N-Acyl amino acid metabolism and piperidine metabolism. Moreover, a combination of 2 gut bacterial genera (Faecalibacterium and Pseudomonas) and 4 metabolites (N-Docosahexaenoyl GABA, 19-Oxoandrost-4-ene-3,17-dione, Trigofoenoside F and 22-Angeloylbarringtogenol C) was able to discriminate AD from NC with AUC of 0.955 in these 65 subjects.ConclusionsThese findings demonstrate that gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD, and suggest that fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.
Highlights
Gut microbiota (GMB) alteration has been reported to influence the Alzheimer’s disease (AD) pathogenesis through immune, endocrine, and metabolic pathways
Xi et al BMC Microbiology (2021) 21:226 in mild cognitive impairment (MCI) patients are similar to that of AD patients compared with normal controls, suggesting the bacterial dysbiosis preceded the onset of dementia [12]
Genera of GMB between AD and normal control (NC) participants After quality filtering and trimming, sequencing of the V3-V4 region of 16S ribosomal RNA (rRNA) gene generated 3.55 million sequence reads from 65 fecal samples with an average length of 419
Summary
Gut microbiota (GMB) alteration has been reported to influence the Alzheimer’s disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. A recent study reported that during AD progression, the alteration of GMB composition leads to the peripheral accumulation of phenylalanine and isoleucine and the increase of pro-inflammatory T helper 1 cell frequency in the blood in AD mouse models, which were observed in MCI due to AD in human [26]. Based on these findings, we sought to investigate potentially ADrelevant gut microbes and their metabolic outputs [27], which has rarely been reported in AD
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