Stratification of the Gut Microbiota Composition Landscape across the Alzheimer's Disease Continuum in a Turkish Cohort

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yıldırım S, Nalbantoğlu ÖU, Bayraktar A, Ercan FB, Gündoğdu A, Velioğlu HA, Göl MF, Soylu AE, Koç F, Gülpınar EA, Kadak KS, Arıkan M, Mardinoğlu A, Koçak M, Köseoğlu E, Hanoğlu L
Journal
mSystems
Year
2022
Keywords:
16S rRNA, Alzheimer’s disease, brain-gut axis, gut microbiome, gut microbiota, precision medicine, precision nutrition, stratification
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.

Experiment 1


Needs review

Curated date: 2023/09/27

Curator: Janezhang

Revision editor(s): Janezhang, Chikamso, Joan Chuks

Subjects

Location of subjects
Turkey
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Alzheimer's disease [X]Dementia in Alzheimer's disease,[X]Dementia in Alzheimer's disease (disorder),AD,AD - Alzheimer's disease,Alzheimer Dementia,Alzheimer dementia,Alzheimer Dementia, Presenile,ALZHEIMER DIS,Alzheimer Disease,Alzheimer disease,Alzheimer disease, familial,Alzheimer Type Dementia,Alzheimer's,Alzheimer's Dementia,Alzheimer's dementia,Alzheimer's disease,Alzheimer's disease (disorder),Alzheimer's disease, NOS,Alzheimers,Alzheimers Dementia,Alzheimers dementia,ALZHEIMERS DIS,Alzheimers disease,DAT - Dementia Alzheimer's type,Dementia in Alzheimer's disease,Dementia in Alzheimer's disease (disorder),Dementia in Alzheimer's disease, unspecified (disorder),Dementia of the Alzheimer's type,Dementia, Alzheimer Type,Dementia, Presenile,Dementia, Presenile Alzheimer,Disease, Alzheimer,Disease, Alzheimer's,Presenile Alzheimer Dementia,sporadic Alzheimer's disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-demented Controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Alzheimer's disease patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Alzheimer's disease, mostly exhibiting mild to very mild dementia
Group 0 sample size Number of subjects in the control (unexposed) group
51
Group 1 sample size Number of subjects in the case (exposed) group
47
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Kruskall-Wallis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
diet
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, education level, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Needs review

Curated date: 2023/10/24

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Source: Supplementary Table S2C

Description: Differentially Abundant Genus level Taxa Between Alzheimer's disease Patients and Non-demented control groups Detected by Limma-Voom Model (Age and Sex Adjusted)

Abundance in Group 1: increased abundance in Alzheimer's disease patients

NCBI Quality ControlLinks
Collinsella
Odoribacter
Parabacteroides
Paraprevotella
Prevotella
unclassified Erysipelotrichaceae
Escherichia/Shigella sp.

Revision editor(s): Joan Chuks

Signature 2

Needs review

Curated date: 2023/10/24

Curator: Joan Chuks

Revision editor(s): Joan Chuks, Iram jamshed

Source: Supplementary Table S2C

Description: Differentially Abundant Genus level Taxa Between Alzheimer's disease Patients and Non-demented control groups Detected by Limma-Voom Model (Age and Sex Adjusted)

Abundance in Group 1: decreased abundance in Alzheimer's disease patients

NCBI Quality ControlLinks
Butyricicoccus
Erysipelotrichaceae
Lachnospiraceae
Parasutterella
unclassified Mollicutes

Revision editor(s): Joan Chuks, Iram jamshed

Experiment 2


Needs review

Curated date: 2023/10/24

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Mild Cognitive Impairment group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Amnestic patients with mild cognitive impairment (MCI)
Group 1 sample size Number of subjects in the case (exposed) group
27

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
increased
Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Needs review

Curated date: 2023/10/24

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Source: Supplementary Table S2D

Description: Differentially Abundant Genus level Taxa Between mild cognitive impairment (MCI) and Non-demented Control (C) groups Detected by Limma-Voom Model (Age and Sex Adjusted)

Abundance in Group 1: increased abundance in Mild Cognitive Impairment group

NCBI Quality ControlLinks
Catenisphaera
Parabacteroides
Clostridium_sensu_stricto_1Clostridium_sensu_stricto_1
Prevotella

Revision editor(s): Joan Chuks

Signature 2

Needs review

Curated date: 2023/10/24

Curator: Joan Chuks

Revision editor(s): Joan Chuks, ChiomaBlessing

Source: Supplementary Table S2D

Description: Differentially Abundant Genus level Taxa Between mild cognitive impairment (MCI) and Non-demented Control (C) groups Detected by Limma-Voom Model (Age and Sex Adjusted)

Abundance in Group 1: decreased abundance in Mild Cognitive Impairment group

NCBI Quality ControlLinks
Butyricicoccus
Parasutterella
Ruminococcaceae bacterium UCG-005
unclassified Mollicutes
uncultured Clostridium sp.
uncultured Lachnospiraceae bacterium
uncultured Erysipelotrichaceae bacterium

Revision editor(s): Joan Chuks, ChiomaBlessing