Gut microbiome and metabolites linked to short-term mortality in cardiogenic shock
D Messiha, M Rinke, M Feike, U B Hendgen Cotta, E Lange, A Westendorf, J Buer, S Lenz, J Kehrmann, P Luedike, V Rudolph, A Haghikia, T Rassaf, C RammosAbstract
Background
Cardiogenic shock represents the severest form of acute circulatory failure and remains associated with high mortality despite advances in supportive care. Beyond hemodynamics, inflammation and metabolic dysregulation are recognized as contributors to multi-organ failure. 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 inflammation and cardiovascular disease. However, their role in shock is poorly understood.
Purpose
To investigate whether gut microbiome and microbiome-derived metabolites are associated with 30-day mortality in patients with cardiogenic shock.
Methods
In this prospective, cross-sectional trial, patients with cardiogenic shock were enrolled within 24 hours of admission. Forty patients (28 male, median age 64 years) were included; 73% presented after cardiac arrest and 58% had infarct-related cardiogenic shock. Stool and peripheral blood samples were collected at baseline and after 72 hours. Gut microbiome composition was assessed using 16S rRNA gene sequencing, and microbiome-derived metabolites were quantified. Systemic inflammatory markers were measured. Thirty-day survival was defined as the primary outcome.
Results
At 30 days, 19 patients survived and 21 died. Baseline characteristics did not differ. Overall microbial diversity was comparable; however, non-survivors exhibited a four-fold enrichment of Clostridiales. Non-survivors demonstrated significantly higher TMAO concentrations and an unfavorable SCFA profile, characterized by reduced isovaleric and valeric acids. Procalcitonin levels were significantly elevated in non-survivors, with trends toward higher hs-CRP and IL-6.
Conclusions
Distinct gut microbiome and metabolite signatures are associated with mortality in shock. Elevated TMAO, altered SCFA composition, and enrichment of Clostridiales reflect gut–heart–immune interactions that contribute to reduced survival. These findings warrant larger mechanistic studies and exploration of microbiome-targeted interventions in cardiogenic shock.