Interaction of gut microbiota-derived metabolites with inflammatory markers and cellular rejection in advanced heart failure patients treated with heart transplantation

Background Disorders of the homeostasis of the gut microbiota, by increasing inflammatory processes, play an important role in the pathophysiology of heart failure (HF) and may affect patients with advanced HF stages who underwent heart transplantation (HTx). An important role may be played by trimethylamine oxide (TMAO), indoxyl sulphate, p-cresyl, which are products of intestinal bacterial metabolism. Purpose The aim of this project was to evaluate gut microbiota key metabolites and its relationship with inflammatory reaction and the occurrence of acute cellular rejection (ACR) in patients treated with Htx. Methods The TMAO, indoxyl sulphate, p-cresyl were evaluated in the serum before Htx, and 1-, 3- and 6- months after Htx. The ACR was established based on the endomyocardial biopsies. Results The study group consisted of thirty-two (78% male, 52±11 years old) patients. Baseline levels of TMAO 0.77[0.52-1.45] ug/mL and p-cresyl 9.90[4.03-18.21] ug/mL were significantly higher than in the healthy control 0.28[0.15-0.51] ug/mL, 4.45[0.79-8.35] ug/mL respectively (all p<0.05). Significant correlations were found for baseline TMAO, p-cresyl, indoxyl sulphate each other, 1-,3- and 6-months indoxyl sulphate and p-cresyl and 6-months TMAO and indoxyl sulphate, TMAO and procalcitonine (all p<0.05). The study group didn’t show significant changes of metabolites in the follow-up period. Patients who experienced ACR had higher p-cresyl sulphate at baseline when compared with group without ACR. Conclusions TMAO, p-cresyl are increased in advanced HF patients. There is no association of microbiota metabolites with inflammation. However, there is possible interaction between incidents of ACR with p-cresyl sulphate.