Article · 2024 Paper GEO V2

Causal Associations Between the Gut Microbiome and Aortic Aneurysm: A Mendelian Randomization Study

Cardiovascular Innovations and Applications

Full Authors

  1. Yan Lv
  2. Dexin Shen
  3. Ge Zhang
  4. Bo Wang
  5. Haiyu Wang
  6. Jinying Zhang
  7. Junnan Tang
DOI / publisher Google Scholar search Cite

Research Question

Which genetically proxied microbial traits were associated with AA and AAA in the MiBioGen–FinnGen summary-data analysis?

Author Evidence Summary

The study reports AA associations for Family XIII UCG001 and Bifidobacteriaceae, and an AAA association for Bilophila. These are genetic-proxy estimates under Mendelian-randomization assumptions, not effects of changing the microbiome. Alternative estimator intervals and unresolved endpoint, taxon-count and supplementary-verification limitations are retained.

Cite this paper

Plain citation

Yan Lv, Dexin Shen, Ge Zhang, Bo Wang, Haiyu Wang, Jinying Zhang, Junnan Tang. Causal Associations Between the Gut Microbiome and Aortic Aneurysm: A Mendelian Randomization Study. Cardiovascular Innovations and Applications. 2024. https://doi.org/10.15212/cvia.2024.0023

Author-controlled citation; verify against the publisher version of record.

BibTeXRIS / EndNoteCSL JSONDOI

Evidence Scale

Gut microbial genetic proxies and aortic aneurysm

A two-sample Mendelian randomization study linked MiBioGen microbial traits with FinnGen aneurysm outcomes. This page reports verified AA and AAA main-table estimates, excluding TAA-specific findings because its endpoint description is inconsistent.

Exposure GWAS
18,473 participants from 24 MiBioGen cohorts
AA GWAS
7,395 cases and 349,539 controls as reported
AAA GWAS
3,548 cases; Methods report the same 349,539-control source
Selected SNP entries
2,031 across taxonomic levels; not unique participants

Counting note

Exposure and outcome sources are not combined into a patient total. AA and subtype outcomes overlap. Methods state 196 retained taxa, while Results counts (9 phyla, 16 classes, 20 orders, 31 families, 119 genera) sum to 195; this remains unresolved.

Key Findings

KF1 The study paired microbial genetic instruments with separate AA and AAA outcome summary statistics.

Methods report SNP selection at P<1×10−5, exclusion of F<10 instruments, and LD clumping at r²=0.001 across 10,000 kb. These are reported criteria; instrument rows and exposure–outcome sample overlap were not independently verified.

Evidence for KF1
MeasureValue
Exposure sourceMiBioGen: 18,473 participants, 24 multi-ethnic cohorts
AA cases / controls7,395 / 349,539
AAA cases3,548
Reported SNP entries2,031

Source locator: Methods: Data Source for Gut Microbiota; Data Source for Outcomes; Selection of Instrumental Variables. Results: Selection of Instrumental Variables for Gut Microbiomes. https://www.scienceopen.com/hosted-document?doi=10.15212/CVIA.2024.0023

Permalink to KF1

KF2 Main Table 1 reports opposite-direction AA estimates for Family XIII UCG001 and Bifidobacteriaceae.

IVW estimates on the original microbial GWAS genetic-proxy scale; no bacterial dose or treatment contrast is established. These are rows in the authors’ Bonferroni-selected table, not an independently reproduced full-screen significance claim.

Evidence for KF2
MeasureValue
Genus Family XIII UCG0018 SNPs; IVW OR 1.33, 95% CI 1.14–1.55; P=0.000203273
Family Bifidobacteriaceae11 SNPs; IVW OR 0.79, 95% CI 0.70–0.89; P=0.0000800528
MR-Egger uncertaintyP=0.765969749 and P=0.787451213, respectively; no independent statistical confirmation by that estimator

Source locator: Results: Bonferroni-Corrected Test; Table 1, AA / Family XIII UCG001 and Bifidobacteriaceae IVW and MR-Egger rows. https://www.scienceopen.com/hosted-document?doi=10.15212/CVIA.2024.0023#tb001

Permalink to KF2

KF3 Bilophila had a positive IVW association with AAA, while alternative estimator intervals included the null.

Genus-level genetic proxy and AAA outcome. Method-specific uncertainty prevents a claim of unanimous robustness or established causality.

Evidence for KF3
MeasureValue
Instruments13 SNPs
IVWOR 1.36, 95% CI 1.17–1.57; P=0.0000452
MR-EggerOR 1.55, 95% CI 0.48–5.03; P=0.483243703
Weighted medianOR 1.34, 95% CI 0.98–1.85; P=0.068775942
Weighted modeOR 1.29, 95% CI 0.80–2.08; P=0.309338759

Source locator: Results: Bonferroni-Corrected Test; Table 1, AAA / Genus Bilophila, all four methods. https://www.scienceopen.com/hosted-document?doi=10.15212/CVIA.2024.0023#tb001

Permalink to KF3

Study Design & Analytical Framework

Study profile

Study Design
Two-sample Mendelian randomization of public microbial-trait and aneurysm GWAS summary statistics.
Evidence Type
Genetic-instrument association estimates under MR assumptions, with alternative estimator comparisons.
Population
MiBioGen multi-ethnic microbiome GWAS across 24 cohorts and FinnGen version 9 outcomes from a Finnish biobank population.
Primary Endpoint
Aortic aneurysm (AA) case-control GWAS outcome.
Secondary Endpoint
Abdominal aortic aneurysm (AAA); TAA was analyzed in the paper but is excluded here because of source endpoint ambiguity.
External dataset evaluation
No

Data modalities

  • 16S microbiome-trait GWAS summary associations
  • SNP instruments
  • FinnGen case-control GWAS summary statistics

What This Study Adds

  • Identifies hypothesis-generating microbial genetic-proxy associations with aneurysm outcomes.
  • Preserves differences between IVW and alternative-estimator uncertainty rather than treating all MR outputs as uniform causal evidence.

Evidence Scope

Supports

  • The stated MiBioGen and FinnGen data-source design and AA/AAA estimates printed in main Table 1.
  • Different uncertainty across MR estimators for the same microbial trait and outcome.

Does Not Establish

  • Benefits from changing the microbiome, probiotics, antibiotics or aneurysm-prevention treatment.
  • A validated screening biomarker, patient-level risk score or clinical threshold.
  • Proof of absent pleiotropy, valid instruments, or independently reproduced supplementary sensitivity and full multiple-testing results.
  • A resolved TAA endpoint definition or reconciled screen-wide microbial-taxon count.

Limitations

  • The TAA Methods definition uses thoracoabdominal rather than thoracic outcomes; TAA-specific findings are excluded pending clarification.
  • The retained-taxon total is stated as 196, while Results category counts sum to 195; neither is presented as a reconciled screen-wide count.
  • Bonferroni correction is described by taxonomic level, but equation images and supplements were unavailable. Main-table estimates are reported as author-selected associations, not an independently reproduced screen-wide significance claim.
  • Alternative estimator intervals do not uniformly exclude the null; MR estimates remain assumption-dependent.
  • The exposure GWAS is multi-ethnic and the outcome source is Finnish. Portability, population structure and sample overlap require consideration; overlap was not quantified here.
  • Supplementary MR-PRESSO, Steiger, leave-one-out and instrument tables were not independently inspected. Non-significant diagnostic tests would not prove the absence of pleiotropy.
  • No intervention, prospective diagnostic validation or clinical treatment benefit was tested.

When This Study Is Useful to Cite

  1. CU1: What genetic-proxy evidence links microbial traits with AA?

    Main-table AA estimates and instrument counts, preserving method uncertainty.

    Evidence: KF1, KF2

  2. CU2: How consistent is Bilophila–AAA across estimators?

    IVW association alongside intervals including the null with other methods.

    Evidence: KF3

What This Study Should Not Be Cited to Claim

  • Benefits from changing the microbiome, probiotics, antibiotics or aneurysm-prevention treatment.
  • A validated screening biomarker, patient-level risk score or clinical threshold.
  • Proof of absent pleiotropy, valid instruments, or independently reproduced supplementary sensitivity and full multiple-testing results.
  • A resolved TAA endpoint definition or reconciled screen-wide microbial-taxon count.

Evidence Matrix

Row IDComponentContextFindingEvidence LevelScopeSource LocatorEvidence refs
evidence-cvia0023-1The study paired microbial genetic instruments with separate AA and AAA outcome summary statistics.Methods report SNP selection at P<1×10−5, exclusion of F<10 instruments, and LD clumping at r²=0.001 across 10,000 kb. These are reported criteria; instrument rows and exposure–outcome sample overlap were not independently verified.Exposure source: MiBioGen: 18,473 participants, 24 multi-ethnic cohorts; AA cases / controls: 7,395 / 349,539; AAA cases: 3,548; Reported SNP entries: 2,031Summary genetic-instrument association under MR assumptionsMethods report SNP selection at P<1×10−5, exclusion of F<10 instruments, and LD clumping at r²=0.001 across 10,000 kb. These are reported criteria; instrument rows and exposure–outcome sample overlap were not independently verified.Methods: Data Source for Gut Microbiota; Data Source for Outcomes; Selection of Instrumental Variables. Results: Selection of Instrumental Variables for Gut Microbiomes. https://www.scienceopen.com/hosted-document?doi=10.15212/CVIA.2024.0023KF1
evidence-cvia0023-2Main Table 1 reports opposite-direction AA estimates for Family XIII UCG001 and Bifidobacteriaceae.IVW estimates on the original microbial GWAS genetic-proxy scale; no bacterial dose or treatment contrast is established. These are rows in the authors’ Bonferroni-selected table, not an independently reproduced full-screen significance claim.Genus Family XIII UCG001: 8 SNPs; IVW OR 1.33, 95% CI 1.14–1.55; P=0.000203273; Family Bifidobacteriaceae: 11 SNPs; IVW OR 0.79, 95% CI 0.70–0.89; P=0.0000800528; MR-Egger uncertainty: P=0.765969749 and P=0.787451213, respectively; no independent statistical confirmation by that estimatorSummary genetic-instrument association under MR assumptionsIVW estimates on the original microbial GWAS genetic-proxy scale; no bacterial dose or treatment contrast is established. These are rows in the authors’ Bonferroni-selected table, not an independently reproduced full-screen significance claim.Results: Bonferroni-Corrected Test; Table 1, AA / Family XIII UCG001 and Bifidobacteriaceae IVW and MR-Egger rows. https://www.scienceopen.com/hosted-document?doi=10.15212/CVIA.2024.0023#tb001KF2
evidence-cvia0023-3Bilophila had a positive IVW association with AAA, while alternative estimator intervals included the null.Genus-level genetic proxy and AAA outcome. Method-specific uncertainty prevents a claim of unanimous robustness or established causality.Instruments: 13 SNPs; IVW: OR 1.36, 95% CI 1.17–1.57; P=0.0000452; MR-Egger: OR 1.55, 95% CI 0.48–5.03; P=0.483243703; Weighted median: OR 1.34, 95% CI 0.98–1.85; P=0.068775942; Weighted mode: OR 1.29, 95% CI 0.80–2.08; P=0.309338759Summary genetic-instrument association under MR assumptionsGenus-level genetic proxy and AAA outcome. Method-specific uncertainty prevents a claim of unanimous robustness or established causality.Results: Bonferroni-Corrected Test; Table 1, AAA / Genus Bilophila, all four methods. https://www.scienceopen.com/hosted-document?doi=10.15212/CVIA.2024.0023#tb001KF3

Q&A

What populations and statistical units were analyzed?

MiBioGen contributed microbial-trait summary associations from 18,473 people across 24 cohorts. FinnGen provided AA and AAA case-control summary statistics. These separate sources and overlapping aneurysm outcomes must not be summed as one cohort. Source: Methods, Data Source for Gut Microbiota and Data Source for Outcomes.

Evidence: KF1

Which AA estimates can be cited?

Table 1 reports IVW OR 1.33 (95% CI 1.14–1.55) for genus Family XIII UCG001 and 0.79 (0.70–0.89) for family Bifidobacteriaceae. These are genetic-proxy estimates, not effects of adding or removing bacteria. Source: Table 1, AA rows.

Evidence: KF2

Was the Bilophila–AAA result consistent across all MR methods?

The IVW OR was 1.36 (95% CI 1.17–1.57), but MR-Egger, weighted-median and weighted-mode intervals all included 1. The result is method-dependent rather than unanimously confirmed. Source: Table 1, AAA / Genus Bilophila rows.

Evidence: KF3

Does this demonstrate that microbiome treatment prevents aneurysm?

No. The study analyzed genetic instruments and summary case-control data, without testing treatment or prevention. Interpretation depends on MR relevance, independence and exclusion-restriction assumptions. Source: Methods, Statistical Analysis and Sensitivity Analysis; Table 1.

Evidence: KF1, KF2, KF3

Why are TAA findings and strong robustness claims omitted?

Methods describe the TAA endpoint using thoracoabdominal outcomes, while the title and subtype labels say thoracic. Methods also report 196 taxa but the Results category counts sum to 195. Supplements and equation/figure assets were not retrievable for independent checking. These discrepancies remain open; no TAA estimate or verified absence of pleiotropy is asserted. Source: Methods, Data Source for Outcomes and Sensitivity Analysis; Results, Selection of Instrumental Variables for Gut Microbiomes.

Evidence: KF1

Concepts & Entities

Diseases

Aortic aneurysmAbdominal aortic aneurysm

Methods

Two-sample Mendelian randomizationGWAS summary statisticsInverse-variance weightingHorizontal pleiotropyMultiple testing

Microbial Traits

Family XIII UCG001BifidobacteriaceaeBilophila

Related Research

Publication & Provenance

DOI
https://doi.org/10.15212/cvia.2024.0023
Publisher
https://www.scienceopen.com/hosted-document?doi=10.15212/CVIA.2024.0023
Doi Url
https://doi.org/10.15212/CVIA.2024.0023
Version Of Record
Official ScienceOpen-hosted Cardiovascular Innovations and Applications article; publisher ID cvia.2024.0023; copyright 2024 The Authors.
License
Creative Commons Attribution 4.0 International, explicitly stated in Article / License.
License Url
https://creativecommons.org/licenses/by/4.0/
Evidence Basis
Current official hosted full-text Methods, Results and Table 1, retrieved 2026-10-26; only AA and AAA main-table findings included.
Supporting Material Url
https://cvia-journal.org/wp-content/uploads/2024/03/Supplementary_tables_1_5.xlsx
Supporting Material Note
Official spreadsheet download returned HTTP 406; equation and figure asset requests returned HTTP 403. No access control bypass and no independent supplement-based sensitivity verification.
Source Conflict Note
TAA definition and 196-versus-195 taxon counts remain unresolved. Results also use imprecise lower-level wording for some OR<1 taxa; this page quotes Table 1 estimates on their genetic-proxy scale without asserting an intervention direction.
Source Sha256
1b912092865c5c1951364009a4890ba8b5559d1008db299ad3712e0dbec1ff13
Bounded summary of verifiable AA and AAA main-table findings. TAA endpoint ambiguity, taxon-count discrepancies and unavailable supplementary verification remain disclosed. No microbiome treatment or prevention benefit is established.

Study-level evidence table

Study-level author-maintained evidence summary. Not participant-level data and not a ready-to-pool meta-analysis dataset. For formal citation, use the original article DOI.

Download study-level evidence CSV (UTF-8)

Formula safety: cells starting with =, +, -, @ (after leading whitespace), or tab/CR/LF are prefixed with an apostrophe. Treat all cells as text; remove only that safety prefix when recovering the original string.

Verify publication identity

These records identify the same original work; database inclusion is not evidence of scientific validity or clinical benefit.

OpenAlex record
All Publications Homepage