Structural and Functional Dysbiosis of Fecal Microbiota in Chinese Patients With Alzheimer's Disease

Study information

Reviewed Marked as Reviewed by Atrayees on 2023-6-1

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

33614635

DOI Digital object identifier for electronic documents.

https://doi.org/10.3389/fcell.2020.634069

URI

https://www.frontiersin.org/articles/10.3389/fcell.2020.634069

Authors

Ling Z, Zhu M, Yan X, Cheng Y, Shao L, Liu X, Jiang R, Wu S

Journal

Frontiers in cell and developmental biology

Year

2020

Keywords:

Alzheimer's disease, Bifidobacterium, Faecalibacterium, gut-brain axis, sequencing

Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut-brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as Faecalibacterium decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as Bifidobacterium, increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients.

Experiment 1

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Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/11

Curator: Sophy

Revision editor(s): WikiWorks, Mcarlson, Sophy, Atrayees, Aiyshaaaa

Subjects

Location of subjects: China

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,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy 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

Group 0 sample size Number of subjects in the control (unexposed) group: 71

Group 1 sample size Number of subjects in the case (exposed) group: 100

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month including prebiotic, probiotic or synbiotic use.

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: LEfSe

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)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3

Matched on Factors on which subjects have been matched on in a case-control study: age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Richness Number of species: decreased

Signature 1

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Source: Figure 2

Description: Differential bacterial taxa between the Chinese AD patients and the healthy controls

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

NCBI	Quality Control	Links
Actinomycetales
Actinomycetota
Akkermansia
Bacilli
Bifidobacteriales
Bifidobacterium
Coriobacteriales
Corynebacteriaceae
Corynebacterium
Enterococcaceae
Enterococcus
Erysipelotrichia
Eubacteriaceae
Eubacterium
Lactobacillaceae
Lactobacillus
Subdoligranulum
Verrucomicrobiaceae
Verrucomicrobiia
Verrucomicrobiales
Verrucomicrobium
Clostridium sp. MCF-1
Alkaliphilus crotonatoxidans
Clostridium sp. DL-VIII

Revision editor(s): WikiWorks, Mcarlson, Sophy, Atrayees, Peace Sandy

Signature 2

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Reviewed Marked as Reviewed by Atrayees on 2023-6-1

Curated date: 2023/03/11

Curator: Sophy

Revision editor(s): WikiWorks, Mcarlson, Sophy, Atrayees, Peace Sandy

Source: Figure 2

Description: Differential bacterial taxa between the Chinese AD patients and the healthy controls

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

NCBI	Quality Control	Links
Anaerostipes
Bacillota
Butyricicoccus
Clostridia
Clostridiaceae
Coprococcus
Dialister
Eubacteriales
Faecalibacterium
Fusicatenibacter
Gemmiger
Lachnospiraceae
Prevotella
Prevotellaceae
Romboutsia
Roseburia
Veillonella

Revision editor(s): WikiWorks, Mcarlson, Sophy, Atrayees, Peace Sandy