Study Identifies Potential Link Between Gut Microbiome and Atherosclerosis

Tove Fall, PhD
Credit: Uppsala University

An analysis of data from nearly 9000 patients is shedding light on a potential link between gut microbiota and the development of atherosclerosis.

Leveraging data from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) cohort, results of the study provide evidence of associations for Streptococcus anginosus and Streptococcusoralis subsp oralis with subclinical coronary atherosclerosis, which investigators suggest warrants further investigation to better understand the potential implications of these findings.¹

“We found that oral bacteria, especially species from the Streptococcus genus, are associated with increased occurrence of atherosclerotic plaques in the small arteries of the heart when present in the gut flora. Species from the Streptococcus genus are common causes of pneumonia and infections of the throat, skin and heart valves. We now need to understand whether these bacteria are contributing to atherosclerosis development,” said lead investigator Tove Fall, PhD, professor in Molecular Epidemiology at the Department of Medical Sciences and the SciLifeLab of Uppsala University.²

Few topics have attracted the attention of the medical communities as the gut microbiome. In 2019, the National Institutes of Health launched the Human Microbiome Project, which is a 10-year, $215-million initiative created with the intent of developing research resources for the field of human microbiome research.³

Citing the limitations of previous studies and an interest in further exploring potential associations between gut microbiome and atherosclerosis, the current study was designed as an analysis of the SCAPIS cohort by Fall and investigators from Lund University. A population-based study of more than 30,000 individuals aged 50-64 years from Sweden, the cohort contained data related to 8973 participants without overt atherosclerotic cardiovascular disease. Additional inclusion criteria for the study required patients to have fecal metagenomics data and coronary artery calcium scores.¹

The study cohort had a mean age of 57.4 years and 53.75 were female. Investigators pointed out coronary artery calcification was detected in 40.3% of participants, with 5.4% having at least 1 stenosis with more than 50% occlusion.¹

For the purpose of analysis, gut microbiota species abidance and functional potential were assessed with shotgun metagenomics sequencing of stool. Investigators estimated associations between species abundance and functional potential with coronary atherosclerosis using multivariable regressions models, with adjustment for cardiovascular risk factors. Investigators also noted plans to assess associated species for association with inflammatory markers, metabolites, and corresponding species in saliva. Of note, oral samples were obtained from saliva samples collected from the Malmö Offspring Study and Malmö Offspring Dental Study.¹

Upon analysis, results indicated 64 species were associated with coronary artery calcium scores in adjusted models. The strongest associations were observed Streptococcus anginosus and Streptococcus oralissubsporalis (P <1×10–5). Investigators pointed out 19 of the 64 species were also found in the oral cavity and were associated with hsCRP plasma concentrations. Additionally, 16 of the 64 species were associated with neutrophil counts.¹

Further analysis indicated some gut microbial species found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Additionally, investigators pointed out 5 species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Investigators also highlighted microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium scores.¹

“We have just started to understand how the human host and the bacterial community in the different compartments of the body affect each other. Our study shows worse cardiovascular health in carriers of streptococci in their gut. We now need to investigate if these bacteria are important players in atherosclerosis development,” said senior investigator Marju Orho-Melander, PhD, MSc, professor in Genetic Epidemiology at Lund University.²

References:

1. _{Sayols-Baixeras S, Dekkers KF, Baldanzi G, et al. Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort [published online ahead of print, 2023 Jul 12]. Circulation. 2023;10.1161/CIRCULATIONAHA.123.063914. doi:10.1161/CIRCULATIONAHA.123.063914}
2. _{Uppsala University. Gut bacteria linked to fatty deposits in heart arteries. EurekAlert! July 12, 2023. Accessed July 12, 2023. https://www.eurekalert.org/news-releases/995026.}
3. _{NIH Human Microbiome Portfolio Analysis Team. A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016. Microbiome. 2019;7(1):31. Published 2019 Feb 26. doi:10.1186/s40168-019-0620-y}