Pivotal interplays between fecal metabolome and gut microbiome reveal functional signatures in cerebral ischemic stroke

Study information

Reviewed Marked as Reviewed by Peace Sandy on 2024-3-28

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

36209079

DOI Digital object identifier for electronic documents.

doi: 10.1186/s12967-022-03669-0.

URI

https://pubmed.ncbi.nlm.nih.gov/36209079/

Authors

Zhao L, Wang C, Peng S, Zhu X, Zhang Z, Zhao Y, Zhang J, Zhao G, Zhang T, Heng X, Zhang L

Journal

Journal of translational medicine

Year

2022

Keywords:

Gut microbiota, Integrative analysis, Ischemic stroke, Metabolomics, Microbiome

BACKGROUND: Integrative analysis approaches of metagenomics and metabolomics have been widely developed to understand the association between disease and the gut microbiome. However, the different profiling patterns of different metabolic samples in the association analysis make it a matter of concern which type of sample is the most closely associated with gut microbes and disease. To address this lack of knowledge, we investigated the association between the gut microbiome and metabolomic profiles of stool, urine, and plasma samples from ischemic stroke patients and healthy subjects. METHODS: We performed metagenomic sequencing (feces) and untargeted metabolomics analysis (feces, plasma, and urine) from ischemic stroke patients and healthy volunteers. Differential analyses were conducted to find key differential microbiota and metabolites for ischemic stroke. Meanwhile, Spearman's rank correlation and linear regression analyses were used to study the association between microbiota and metabolites of different metabolic mixtures. RESULTS: Untargeted metabolomics analysis shows that feces had the most abundant features and identified metabolites, followed by urine and plasma. Feces had the highest number of differential metabolites between ischemic stroke patients and the healthy group. Based on the association analysis between metagenomics and metabolomics of fecal, urine, and plasma, fecal metabolome showed the strongest association with the gut microbiome. There are 1073, 191, and 81 statistically significant pairs (P < 0.05) in the correlation analysis for fecal, urine, and plasma metabolome. Fecal metabolites explained the variance of alpha-diversity of the gut microbiome up to 31.1%, while urine and plasma metabolites only explained the variance of alpha-diversity up to 13.5% and 10.6%. Meanwhile, there were more significant differential metabolites in feces than urine and plasma associated with the stroke marker bacteria. CONCLUSIONS: The systematic association analysis between gut microbiome and metabolomics reveals that fecal metabolites show the strongest association with the gut microbiome, followed by urine and plasma. The findings would promote the association study between the gut microbiome and fecal metabolome to explore key factors that are associated with diseases. We also provide a user-friendly web server and a R package to facilitate researchers to conduct the association analysis of gut microbiome and metabolomics.

Experiment 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-3-28

Curated date: 2024/03/14

Curator: Adeoyo Olajumoke

Revision editor(s): Adeoyo Olajumoke, Peace Sandy

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 , Urine , Blood plasma 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,Urine,urine,Blood plasm,Plasma,Portion of blood plasma,Portion of plasma,Blood plasma,blood plasma

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Stroke Acute Cerebrovascular Accident,Acute Cerebrovascular Accidents,Acute Stroke,Acute Strokes,Apoplexy,Apoplexy, Cerebrovascular,Brain Vascular Accident,Brain Vascular Accidents,cerebral infarction,Cerebral Stroke,Cerebral Strokes,Cerebrovascular Accident,cerebrovascular accident,Cerebrovascular accident (disorder),Cerebrovascular accident (disorder) [Ambiguous],CEREBROVASCULAR ACCIDENT, (CVA),cerebrovascular accident, (CVA),Cerebrovascular Accident, Acute,Cerebrovascular Accidents,Cerebrovascular Accidents, Acute,Cerebrovascular Apoplexy,Cerebrovascular Apoplexya,Cerebrovascular Stroke,Cerebrovascular Strokes,CVA,CVA (cerebral vascular accident),CVA (Cerebrovascular Accident),CVA - Cerebrovascular accident,CVA - Cerebrovascular accident unspecified,CVA, CEREBROVASCULAR ACCIDENT,CVA, cerebrovascular accident,CVAs (Cerebrovascular Accident),ischemic stroke,stroke,Stroke and cerebrovascular accident unspecified,Stroke and cerebrovascular accident unspecified (disorder),stroke disorder,Stroke NOS,Stroke NOS (disorder),STROKE SYNDROME,stroke syndrome,Stroke, Acute,Stroke, Cerebral,Stroke, Cerebrovascular,Stroke/CVA - undefined,Strokes,Strokes, Acute,Strokes, Cerebral,Strokes, Cerebrovascular,SYNDROME, STROKE,syndrome, stroke,undetermined stroke,Vascular Accident, Brain,Vascular Accidents, Brain,Stroke

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

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with ischemic stroke by skull computed tomography examination who have not experienced any pre-existing metabolic or gut diseases.

Group 0 sample size Number of subjects in the control (unexposed) group: 30

Group 1 sample size Number of subjects in the case (exposed) group: 60

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: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

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)?: Yes

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Alpha Diversity

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

Chao1 Abundance-based estimator of species richness: increased

Richness Number of species: increased

Signature 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-3-28

Curated date: 2024/03/15

Curator: Adeoyo Olajumoke

Revision editor(s): Adeoyo Olajumoke

Source: Figure. 6

Description: Significantly different abundant taxa with LDA score (log10) > 2.0 and P < 0.05

Abundance in Group 1: increased abundance in Cerebral ischemic stroke patients

NCBI	Quality Control	Links
Acetobacter sp. CAG:267
Akkermansia muciniphila CAG:154
Alistipes senegalensis
Alistipes shahii
Azospirillum sp. CAG:239
Bacteroides caccae
Bacteroides oleiciplenus
Clostridium sp. CAG:1024
Clostridium sp. CAG:226
Clostridium sp. CAG:715
Coraliomargarita sp. CAG:312
Desulfovibrio piger
Dorea sp. CAG:105
Eubacterium limosum
Leyella stercorea CAG:629
Odoribacter splanchnicus
Oscillibacter sp. CAG:241
Oscillibacter sp. ER4
Prevotella amnii
Ruminococcus sp. CAG:488
Oscillibacter
Oscillospiraceae bacterium
Alphaproteobacteria
Acetobacter
Coriobacteriaceae
Odoribacter
Collinsella
Desulfovibrio
Opitutia
Puniceicoccaceae
Puniceicoccales
Coraliomargarita
Pasteurellaceae
Pasteurellales