The role of gut microbiota and short-chain fatty acids in patients with advanced heart failure undergoing orthotopic heart transplantation

Background Dysregulation of gut microbiota homeostasis, through increased inflammatory processes, plays a crucial role in the pathophysiology of heart failure (HF) and may impact patients with advanced HF undergoing orthotopic heart transplantation (Htx). A deficiency in short-chain fatty acids (SCFAs), key metabolites of intestinal bacterial activity, may contribute to inflammatory dysregulation and influence post-transplant outcomes. Purpose This study aimed to investigate the relationship between fecal SCFA levels and baseline laboratory parameters in patients qualified for Htx, as well as their association with acute cellular graft rejection at a six-month follow-up. Results Thirty-two patients (87% male, 54±10 years old) were included. Significant correlations were found between baseline laboratory parameters on the day of inclusion: haemoglobin vs. acetic acid (R=0.57), propionic acid (R=0.60), butyric acid (R=0.58); leukocyte count vs. lactic acid (R=0.59); protein level vs. acetic acid (R=0.56) and propionic acid (R=0.46); LDL cholesterol vs. acetic acid (R=0.52); and a negative correlation between NTproBNP levels and butyric acid (R=-0.47), all p<0.05. Patients who developed graft rejection at 6-month follow-up had significantly lower baseline concentrations of (median [IQR]): acetic acid 1.1 [0.9-1.4] vs. 8.2 [4.8-32.0], propionic acid 0.7 [0.6-0.9] vs. 2.5 [2.0-10.0] and butyric acid 0.51 [0.48-0.91] vs. 2.1 [1.5-8.4] µmol/1g stool compared to the group without rejection incidents. Conclusions Fecal SCFA content is associated with inflammatory activity, comorbidities, and HF severity, as reflected by natriuretic peptide levels. Lower baseline SCFA levels were linked to a higher incidence of acute cellular rejection post-transplant, suggesting a potential protective role of SCFAs in modulating immune responses and preventing graft rejection.