Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study.

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  • Additional Information
    • Source:
      Publisher: Oxford Journals Country of Publication: England NLM ID: 0077427 Publication Model: Print Cited Medium: Internet ISSN: 1755-3245 (Electronic) Linking ISSN: 00086363 NLM ISO Abbreviation: Cardiovasc Res Subsets: MEDLINE
    • Publication Information:
      Publication: 2008- : Oxford : Oxford Journals
      Original Publication: London, British Medical Assn.
    • Subject Terms:
      Cardiovascular Diseases*/diagnosis ; Cardiovascular Diseases*/epidemiology ; Cardiovascular Diseases*/microbiology ; Ethnicity* ; Gastrointestinal Microbiome*; Humans ; Bacteria/genetics ; Cross-Sectional Studies ; Genome-Wide Association Study ; Lipids ; Prospective Studies ; Risk Factors ; Netherlands
    • Abstract:
      Aims: Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes.
      Methods and Results: We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated.
      Conclusion: Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae, Methanobrevibacter, and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.
      Competing Interests: Conflict of interest: M.N. is a member of the scientific advisory board of Caelus Health and all honoraria are paid to the employer Amsterdam University Medical Centerr. Karine Clement is a consultant for Danone Research, LNC Therapeutics, and CONFO Therapeutics for work that is unassociated with the present study. K.C. has held a collaborative research contract with Danone Research in the context of the MetaCardis project. All honoraria are paid to the employer Sorbonne University. D.H.v.R. has participated in advisory boards for AstraZeneca, Boehringer Ingelheim-Eli Lilly Alliance, MSD, Novo Nordisk, and Sanofi, and has received research grants from AstraZeneca, Boehringer Ingelheim-Eli Lilly Alliance, MSD, and Sanofi. All honoraria are paid to the employer Amsterdam University Medical Center. All other authors declare having no related conflict of interest.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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    • Grant Information:
      09150182010020 Netherlands ZONMW_ ZonMw
    • Contributed Indexing:
      Keywords: Atherosclerosis; Cardiovascular diseases; HELIUS study; Mendelian randomization; Microbiome; Trophic networks
    • Accession Number:
      0 (Lipids)
    • Publication Date:
      Date Created: 20240130 Date Completed: 20240401 Latest Revision: 20240401
    • Publication Date:
      20240402
    • Accession Number:
      PMC10981523
    • Accession Number:
      10.1093/cvr/cvae018
    • Accession Number:
      38289866