Distinct gut microbiota profiles may characterize amyloid beta pathology and mild cognitive impairment

Abstract Gut microbiome composition has been associated with early preclinical Alzheimer’s disease (AD), as reflected by cerebrospinal fluid (CSF) amyloid beta pathology, and with mild cognitive impairment (MCI). However, the presence of distinct microbiota across different disease stages has not been fully characterized. We profiled gut microbiota in 50 nondemented individuals by 16S ribosomal RNA sequencing and taxonomic profiles were compared between amyloid-based (amyloid-normal vs. amyloid-pathology) and clinically- based (cognitively normal vs. MCI) diagnosis groups using linear models (adjusted for sex, age and diet). Elastic net regression model was used to assess the discriminative performance of microbiota for amyloid-pathology and MCI. Microbial diversity measures did not differ across groups. We identified specific genera associated with amyloid-pathology and MCI such as Oxalobacter, Marvinbryantia and Escherichia-Shigella, mostly linked to inflammation. Distinct genera were found to be unique to amyloid-pathology and MCI. Microbiota was shown to have a fairly good discriminative performance. Overall, we suggest the presence of distinct microbiota in early preclinical stage of AD and MCI, which needs to be further explored. Competing Interest Statement The authors have declared no competing interest. Funding Statement This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Written informed consent was obtained from all participants, and study procedures were approved by the Institutional Review Board and Ethics Committee of the Aiginition University Hospital, National and Kapodistrian University of Athens, Greece (Protocol code: 255, ΑΔΑ: ΨΘ6Κ46Ψ8Ν2-8ΗΩ, date of approval: 10 May 2022). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data used in the analyses of this study are available within the manuscript and its supplemental information files. The raw sequencing data generated from this study have been deposited in NCBI SRA (https://www.ncbi.nlm.nih.gov/sra) under the accession number PRJNA1066101.