Metagenomic study of the MESA: Detection of Gemella morbillorum and association with coronary heart disease

Authors: TAYLOR, KENT - Harbor-Ucla Medical Center; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); ROTTER, JEROME - Harbor-Ucla Medical Center; GUO, XIUQING - Harbor-Ucla Medical Center; HERRINGTON, DAVID - Wake Forest School Of Medicine; JOHNSON, W - University Of Washington; POST, WENDY - Johns Hopkins University School Of Medicine; TRACY, RUSSELL - University Of Vermont; RICH, STEPHEN - University Of Virginia; MALIK, SHAISTA - University Of California Irvine

Submitted to: Journal of the American Heart Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/22/2024
Publication Date: 9/30/2024
Citation: Taylor, K.D., Wood, A.C., Rotter, J.I., Guo, X., Herrington, D.M., Johnson, W.C., Post, W.S., Tracy, R.P., Rich, S.S., Malik, S. 2024. Metagenomic study of the MESA: Detection of Gemella morbillorum and association with coronary heart disease. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.124.035693.
DOI: https://doi.org/10.1161/JAHA.124.035693

Interpretive Summary: Inflammation is a known consequence of excess weight gain, and serves as a risk factor in coronary heart disease (CHD), but how infections from microbes contribute to CHD is not well understood. This study used new sequencing techniques to generate comprehensive data on the presence/absence of genetic material from non-human microbes in the plasma of over 4400 older US adults, in order to find out of there were links between specific microbes and the risk of developing CHD. Two microbes: Gemella morbillorum and Pseudomonas species NFACC19-2. NFACC19-2 were significantly associated with an increased risk of developing CHD. This suggests that these microbes might contribute to the inflammation that leads to heart disease, both of which are health concerns for individuals with obesity. The findings highlight the potential for using advanced genetic techniques to identify harmful pathogens, and suggests that more research into microbes might be informative for understanding the risk of obesity-related outcomes.

Technical Abstract: Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied. CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference. Paired reads aligning to 840 microbes were detected in >1% of participants. The association of the presence of microbe reads with incident CHD (follow-up, ~18 years) was examined. First, important variables were ascertained using a single regularized Cox proportional hazard model, examining change of risk as a function of presence of microbe with age, sex, education level, Life's Simple 7, and inflammation. For variables of importance, the hazard ratio (HR) was estimated in separate (unregularized) Cox proportional hazard models including the same covariates (significance threshold Bonferroni corrected P<6x10**-5, 0.05/840). Reads from 2 microbes were significantly associated with CHD: Gemella morbillorum (HR, 3.14 [95% CI, 1.92-5.12]; P=4.86x10**-6) and Pseudomonas species NFACC19-2 (HR, 3.22 [95% CI, 2.03-5.41]; P=1.58×10**-6). Metagenomics of whole-genome sequence reads opens a possible frontier for detection of pathogens for chronic diseases. The association of G morbillorum and Pseudomonas species reads with CHD raises the possibilities that microbes may drive atherosclerotic inflammation and that treatments for specific pathogens may provide clinical utility for CHD reduction.