kth.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Stratification of the Gut Microbiota Composition Landscape across the Alzheimer's Disease Continuum in a Turkish Cohort
Istanbul Medipol Univ, Dept Med Microbiol, Int Sch Med, Istanbul, Turkey.;Istanbul Medipol Univ, Res Inst Hlth Sci & Technol SABITA, Regenerat & Restorat Med Res Ctr REMER, Istanbul, Turkey..ORCID iD: 0000-0002-2752-1223
Erciyes Univ, Dept Comp Engn, Kayseri, Turkey.;Erciyes Univ, Genome & Stem Cell Ctr GenKok, Kayseri, Turkey..
Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, England..ORCID iD: 0000-0001-5287-5026
Istanbul Medipol Univ, Grad Program Neurosci, Int Sch Med, Istanbul, Turkey..
Show others and affiliations
2022 (English)In: mSystems, E-ISSN 2379-5077, Vol. 7, no 1, article id e00004-22Article in journal (Refereed) Published
Abstract [en]

Alzheimer's disease (AD) is a heterogeneous disorder that spans a continuum with multiple phases, including preclinical, mild cognitive impairment, and dementia. Unlike for most other chronic diseases, human studies reporting on AD gut microbiota in the literature are very limited. With the scarcity of approved drugs for AD therapies, the rational and precise modulation of gut microbiota composition using diet and other tools is a promising approach to the management of AD. Such an approach could be personalized if an AD continuum can first be deconstructed into multiple strata based on specific microbiota features by using single or multiomics techniques. However, stratification of AD gut microbiota has not been systematically investigated before, leaving an important research gap for gut microbiota-based therapeutic approaches. Here, we analyze 16S rRNA amplicon sequencing of stool samples from 27 patients with mild cognitive impairment, 47 patients with AD, and 51 nondemented control subjects by using tools compatible with the compositional nature of microbiota. To stratify the AD gut microbiota community, we applied four machine learning techniques, including partitioning around the medoid clustering and fitting a probabilistic Dirichlet mixture model, the latent Dirichlet allocation model, and we performed topological data analysis for population-scale microbiome stratification based on the Mapper algorithm. These four distinct techniques all converge on Prevotella and Bacteroides stratification of the gut microbiota across the AD continuum, while some methods provided fine-scale resolution in stratifying the community landscape. Finally, we demonstrate that the signature taxa and neuropsychometric parameters together robustly classify the groups. Our results provide a framework for precision nutrition approaches aiming to modulate the AD gut microbiota. IMPORTANCE The prevalence of AD worldwide is estimated to reach 131 million by 2050. Most disease-modifying treatments and drug trials have failed, due partly to the heterogeneous and complex nature of the disease. Recent studies demonstrated that gut dybiosis can influence normal brain function through the so-called "gut brain axis." Modulation of the gut microbiota, therefore, has drawn strong interest in the clinic in the management of the disease. However, there is unmet need for microbiota-informed stratification of AD clinical cohorts for intervention studies aiming to modulate the gut microbiota. Our study fills in this gap and draws attention to the need for microbiota stratification as the first step for microbiota-based therapy. We demonstrate that while Prevotella and Bacteroides clusters are the consensus partitions, the newly developed probabilistic methods can provide fine-scale resolution in partitioning the AD gut microbiome landscape.

Place, publisher, year, edition, pages
The American Society for Microbiology (ASM) , 2022. Vol. 7, no 1, article id e00004-22
Keywords [en]
gut microbiome, Alzheimer's disease, 16S rRNA, stratification, brain-gut nutrition
National Category
Nutrition and Dietetics
Identifiers
URN: urn:nbn:se:kth:diva-310075DOI: 10.1128/msystems.00004-22ISI: 000760774900005PubMedID: 35133187Scopus ID: 2-s2.0-85125143432OAI: oai:DiVA.org:kth-310075DiVA, id: diva2:1645987
Note

QC 20220321

Available from: 2022-03-21 Created: 2022-03-21 Last updated: 2025-02-11Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records

Mardinoglu, Adil

Search in DiVA

By author/editor
Yildirim, SuleymanBayraktar, AbdulahadMardinoglu, Adil
By organisation
Systems BiologyScience for Life Laboratory, SciLifeLab
In the same journal
mSystems
Nutrition and Dietetics

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 38 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf