Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

31063846

DOI Digital object identifier for electronic documents.

https://doi.org/10.1016/j.bbi.2019.05.008

URI

https://www.sciencedirect.com/science/article/pii/S0889159118307190

Authors

Liu P, Wu L, Peng G, Han Y, Tang R, Ge J, Zhang L, Jia L, Yue S, Zhou K, Li L, Luo B, Wang B

Journal

Brain, behavior, and immunity

Year

2019

Keywords:

Alzheimer’s disease, Amnestic mild cognitive impairment, Microbiome marker

OBJECTIVE: (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated. METHODS: A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients. RESULTS: The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC. And the microbial composition was distinct among aMCI, AD and healthy control groups. Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC. In addition, similar alterations were observed at the order, class and family levels of these two phyla. And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients. Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes. Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients. Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925). Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698). CONCLUSIONS: Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects. These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4

Curated date: 2023/03/11

Curator: Sophy

Revision editor(s): Sophy, Claregrieve1

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: 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,alzheimer's disease

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with dementia stage of alzheimer's disease.

Group 0 sample size Number of subjects in the control (unexposed) group: 32

Group 1 sample size Number of subjects in the case (exposed) group: 33

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Two months

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: 2

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: unchanged

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

Richness Number of species: unchanged

Signature 1

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Curated date: 2023/03/12

Curator: Sophy

Revision editor(s): Sophy, Aiyshaaaa, Claregrieve1

Source: Figure 2

Description: Differential microbial abundance between Alzheimers patients and healthy controls

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

NCBI	Quality Control	Links
Bacillota
Bacteroidia
Blautia
Clostridiaceae
Lachnospiraceae
Oscillospiraceae
Ruminococcus
Clostridiales bacterium
Bacteroidales
Bacillus sp. (in: firmicutes)
Clostridia
Enterobacteriaceae

Revision editor(s): Sophy, Aiyshaaaa, Claregrieve1

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4

Curated date: 2023/03/12

Curator: Sophy

Revision editor(s): Sophy, Aiyshaaaa, Claregrieve1

Source: Figure 2

Description: Differential microbial abundance between Alzheimers patients and healthy controls

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

NCBI	Quality Control	Links
Gammaproteobacteria
Pseudomonadota
Enterobacterales
Enterobacteriaceae

Revision editor(s): Sophy, Aiyshaaaa, Claregrieve1

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4

Curated date: 2023/03/25

Curator: Sophy

Revision editor(s): Sophy, Claregrieve1

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies: aMCI patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with amnestic mild cognitive impairment of alzheimer's disease.