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      Gut Microbiota Composition Is Related to AD Pathology

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          Abstract

          Introduction

          Several studies have reported alterations in gut microbiota composition of Alzheimer’s disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD).

          Materials and Methods

          We included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE.

          Results

          The machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis, and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status.

          Conclusions

          Gut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status.

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          Tianqi Chen, Carlos Guestrin (2016)
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            The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

            Marilyn Albert, Steven Dekosky, Dennis D Dickson … (2011)
            The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. Copyright © 2011 The Alzheimer's Association. All rights reserved.
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              Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

              G. McKhann, D. Drachman, M. Folstein … (1984)
              Neurology, 34(7), 939-939
              Article 0 comments Cited 1508 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Immunol
                Journal ID (iso-abbrev): Front Immunol
                Journal ID (publisher-id): Front. Immunol.
                Title: Frontiers in Immunology
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-3224
                Publication date (Electronic): 31 January 2022
                Publication date Collection: 2021
                Volume: 12
                Electronic Location Identifier: 794519
                Affiliations
                [1] 1 Department of Internal Medicine - Geriatrics, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center (UMC) , Amsterdam, Netherlands
                [2] 2 Department of Internal and Vascular Medicine, Amsterdam University Medical Center (UMC) , Amsterdam, Netherlands
                [3] 3 Alzheimer Center, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center (UMC) , Amsterdam, Netherlands
                [4] 4 Department of Clinical Chemistry, Amsterdam University Medical Center (UMC) , Amsterdam, Netherlands
                [5] 5 Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center (UMC) , Amsterdam, Netherlands
                [6] 6 University College London (UCL) Institutes of Neurology, Faculty of Brain Sciences , London, United Kingdom
                [7] 7 Department of Internal Medicine, Erasmus Medical Center (MC) , Rotterdam, Netherlands
                [8] 8 Department of Epidemiology, Erasmus Medical Center (MC) , Rotterdam, Netherlands
                [9] 9 Nuffield Department of Population Health, University of Oxford , Oxford, United Kingdom
                [10] 10 Department of Epidemiology and Data Science, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam , Amsterdam, Netherlands
                Author notes

                Edited by: Guillaume Dorothee, U938 Centre de Recherche Saint Antoine (CRSA) (INSERM), France

                Reviewed by: Nathalie Rolhion, Institut National de la Santé et de la Recherche Médicale (INSERM), France; Laura M. Cox, Harvard Medical School, United States; Barbara B. Bendlin, University of Wisconsin-Madison, United States

                *Correspondence: Barbara J. H. Verhaar, b.j.verhaar@ 123456amsterdamumc.nl

                This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Immunology

                Article
                DOI: 10.3389/fimmu.2021.794519
                PMC ID: 8843078
                PubMed ID: 35173707
                SO-VID: 59836f0b-de8e-4d8a-8b93-dbcd474c75b2
                Copyright © Copyright © 2022 Verhaar, Hendriksen, de Leeuw, Doorduijn, van Leeuwenstijn, Teunissen, Barkhof, Scheltens, Kraaij, van Duijn, Nieuwdorp, Muller and van der Flier
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 13 October 2021
                Date accepted : 31 December 2021
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 63, Pages: 11, Words: 5714
                Categories
                Subject: Immunology
                Subject: Original Research

                ScienceOpen disciplines: Immunology
                Keywords: gut microbiota,microbiome,alzheimer’s disease,amyloid beta,p-tau,mri
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: gut microbiota, microbiome, alzheimer’s disease, amyloid beta, p-tau, mri

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