Ischaemic stroke patients present sex differences in gut microbiota

Study information

Reviewed Marked as Reviewed by Svetlana up on 2025-4-15

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

37329328

DOI Digital object identifier for electronic documents.

https://doi.org/10.1111/ene.15931

URI

Authors

Lledós M, Prats-Sánchez L, Llucià-Carol L, Cárcel-Márquez J, Muiño E, Cullell N, Gallego-Fabrega C, Martín-Campos JM, Aguilera-Simón A, Guasch-Jiménez M, Guisado-Alonso D, Ramos-Pachón A, Martínez-Domeño A, Izquierdo A, Marín R, Camps-Renom P, Martí-Fàbregas J, Fernández-Cadenas I

Journal

European journal of neurology

Year

2023

Keywords:

gut microbiota, gut-brain axis, sex, stroke

BACKGROUND: Gut microbiota plays a role in the pathophysiology of ischaemic stroke (IS) through the bidirectional gut-brain axis. Nevertheless, little is known about sex-specific microbiota signatures in IS occurrence. METHODS: A total of 89 IS patients and 12 healthy controls were enrolled. We studied the taxonomic differences of the gut microbiota between men and women with IS by shotgun metagenomic sequencing. To evaluate the causal effect of several bacteria on IS risk, we performed a two-sample Mendelian randomisation (MR) with inverse-variance weighting (IVW) using genome-wide association analysis (GWAS) summary statistics from two cohorts of 5959 subjects with genetic and microbiota data and 1,296,908 subjects with genetic and IS data, respectively. RESULTS: α-Diversity analysis measured using Observed Species (p = 0.017), Chao1 (p = 0.009) and Abundance-based Coverage Estimator (p = 0.012) indexes revealed that IS men have a higher species richness compared with IS women. Moreover, we found sex-differences in IS patients in relation to the phylum Fusobacteria, class Fusobacteriia, order Fusobacteriales and family Fusobacteriaceae (all Bonferroni-corrected p < 0.001). MR confirmed that increased Fusobacteriaceae levels in the gut are causally associated with an increased risk of IS (IVW p = 0.02, β = 0.32). CONCLUSIONS: Our study is the first to indicate that there are gut microbiome differences between men and women with IS, identifying high levels of Fusobacteriaceae in women as a specific risk factor for IS. Incorporating sex stratification analysis is important in the design, analysis and interpretation of studies on stroke and the gut microbiota.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-15

Curated date: 2025/04/12

Curator: Aiyshaaaa

Revision editor(s): Aiyshaaaa

Subjects

Location of subjects: Spain

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: Ischemic stroke Ischaemic stroke,Ischemic stroke,ischemic stroke

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Male IS patients (Ischemic stroke)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Female IS patients (Ischemic stroke)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Female patients who have been diagnosed with Ischemic stroke

Group 0 sample size Number of subjects in the control (unexposed) group: 53

Group 1 sample size Number of subjects in the case (exposed) group: 36

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).: log transformation

Statistical test: Negative Binomial Regression

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age

Alpha Diversity

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

Chao1 Abundance-based estimator of species richness: decreased

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

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-15

Curated date: 2025/04/12

Curator: Aiyshaaaa

Revision editor(s): Aiyshaaaa

Source: Fig-2b and Table-2

Description: Log-transformed and differential abundance of Fusobacteria (phylum to family level) in between male and female ischemic stroke patients.

Abundance in Group 1: increased abundance in Female IS patients (Ischemic stroke)

NCBI	Quality Control	Links
Fusobacteriaceae
Fusobacteriales
Fusobacteriia
Fusobacteriota

Revision editor(s): Aiyshaaaa