https://doi.org/10.1007/s00392-024-02526-y
1Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland; 2Universität Duisburg-Essen Institut für Immunologie und Mikrobiologie Essen, Deutschland
Background
The acute coronary syndrome (ACS) is a leading cause of morbidity and mortality in the industrialized world. Whereas the pathophysiology is multilayered, current data show that ACS is also an acute inflammatory event. The enteral microbiome as the biggest immunological compartment has the potential to influence various cardiovascular diseases.
The microbiome is a double-edged sword which can convey protective and detrimental cardiovascular effects. While it can promote the development of atherosclerosis through the production of atherogenic metabolites such as trimethylamine N-oxide (TMAO) it can also generate a protective effect through the production of metabolites such as short chain fatty acids (SCFA). The exact mechanisms of interaction between the enteral microbiome, downstream metabolites and ACS have not been elucidated so far.
Purpose
Aim of this study is to determine the long-term impact of acute coronary syndrome (ACS) on the enteral microbiome and downstream microbiome-dependent metabolites.
Methods
We included 20 patients with ACS within the first 24 hours of clinical presentation with a follow-up of 28 days and 15 healthy participants as a control. Analysis of enteral microbiome as well as downstream metabolites and basic cardiovascular diagnostics were performed on day 1, 3, 7, 14 and 28.
Microbiome-dependent metabolites such as TMAO and SCFA were analyzed from peripheral blood samples. Enteral microbiome samples were characterized by DNA isolation and consecutive 16sRNA analysis. Basic cardiovascular diagnostics included blood pressure, pulse wave velocity and global longitudinal strain.
Results
We enrolled a total of 20 patients with 70% male patients and an average age of 66.3 years ±10.8 years.
Alpha diversity of the microbiome, regarding richness and Shannon effective score, did not differ throughout the follow up period of up to 28 days. Longitudinally, after ACS at 28 days, abundance of Marinifilacea on family level (350 ± 262 vs 130 ± 75; p < 0.05) and Butyricimonas on genus level (190 ± 225 vs 30 ± 76; p < 0.05) decreased, whereas abundance of Butyricicoccaceae on family level (120 ± 90 vs 290 ± 225; p < 0.005) and Butyricicoccus on genus level (110 ± 82.5 vs 300 ± 225; p < 0.005) increased.
SCFAs were differentially regulated after ACS, with serum levels of butanoic acid increasing (0.0008 ± 0.0001 mM vs 0.001 ± 0.0004 mM, p < 0.05). TMAO levels did not differ significantly between baseline and follow-up (366 ± 169 mg/l vs 453 ± 180 mg/l; p > 0.05).
Conclusion
In this prospective study we detected a specific long-term enteral regulation in patients with ACS. Correspondingly, ACS patients experienced a differential regulation of the microbiome dependent downstream metabolite SCFA butanoic acid, whereas TMAO levels remained unchanged. Insights into these specific regulations after ACS will help develop custom-tailored approaches to further reduce the burden of acute cardiovascular events.