Background
Cardiogenic shock (CS) represents the most severe form of acute circulatory failure, characterized by profound myocardial dysfunction, systemic hypoperfusion, and high mortality despite advances in supportive care. Beyond hemodynamic collapse, systemic inflammation and metabolic dysregulation are increasingly recognized as key drivers of multi-organ failure in cardiogenic shock. The gut–heart axis has emerged as a potential modulator of cardiovascular outcomes, with microbiome-derived metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) implicated in atherosclerosis and heart failure. However, the role of gut microbiome composition and metabolite profiles in cardiogenic schock remains poorly understood.
Methods
In this prospective, cross-sectional clinical trial, we enrolled 40 patients with cardiogenic shock within 24 hours of admission. Stool and peripheral blood samples were collected at baseline and after 72 hours. Gut microbiome composition was assessed by 16S rRNA gene sequencing, while microbiome-derived metabolites (TMAO and SCFAs) were quantified using liquid chromatography–mass spectrometry. Systemic inflammatory markers were measured in parallel. Clinical outcome was defined as 30-day survival.
Results
At 30 days, 19 patients survived and 21 died. While overall microbial diversity did not differ, non-survivors exhibited a four-fold enrichment of Clostridiales compared with survivors. Non-survivors also displayed significantly higher plasma TMAO levels at both time points and an unfavorable SCFA profile, characterized by reduced isovaleric and valeric acids. Furthermore, procalcitonin was significantly elevated in non-survivors, with trends toward higher hs-CRP and IL-6.
Conclusion
Distinct gut microbiome and metabolite signatures are associated with mortality in CS. Elevated TMAO, altered SCFA composition, and enrichment of Clostridiales may reflect gut–heart–immune interactions that contribute to poor outcomes. These findings warrant larger mechanistic studies and exploration of microbiome-targeted interventions in cardiogenic schock.
