Bile acid profiles in heart transplant recipients and their association with acute cellular rejection

Background Bile acids (BAs) are involved in lipid metabolism and also play a signaling role through interactions with plasma membrane and nuclear receptors. Primary BAs are synthesized in the liver and subsequently transformed into secondary BAs by intestinal microorganisms. BAs participate in immune regulation by modulating inflammatory pathways, immune cell activation, and cytokine production. Through these mechanisms, they may influence systemic inflammation and contribute to the pathophysiology of heart failure (HF). However, they have not been well characterized in patients with advanced HF who undergo heart transplantation (HTx), where immunological mechanisms play a key role in post-transplant outcome. Purpose The aim of this study was to investigate BA profiles in patients treated with Htx and assess whether specific BA are associated with acute cellular rejection (ACR). Methods Primary BAs, their conjugated metabolites, and secondary BAs were quantified using liquid chromatography-mass spectrometry in serum samples collected before HTx and at 1, 3, and 6 months after HTx. ACR was diagnosed based on endomyocardial biopsy. Results The study group consisted of 32 patients (78% male, mean age 52 ± 11 years). Baseline levels of taurochenodeoxycholic acid (TCDCA) were significantly higher in the study group compared with healthy controls [758.03 (228.26–3172.77) ng/mL vs 258.63 (156.27–661.31) ng/mL, p = 0.04]. Patients undergoing HTx did not show significant changes in BA levels during the follow-up period. However, patients who developed ACR in the months following BA measurement had significantly higher glycochenodeoxycholic acid (GCDCA) levels at 1 month after HTx compared with the non-ACR group [4011.04 (2887.74–18304.74) ng/mL vs 1313.92 (888.32–2898.50) ng/mL, p = 0.01]. Conclusions The Htx group was characterized by higher TCDCA levels compared with controls. Although patients after Htx did not exhibit significant changes in BA levels, higher GCDCA concentrations one month after Htx were associated with subsequent ACR. These findings generate a hypothesis that specific alterations in conjugated BAs metabolism may contribute to the BA profile observed in patients with advanced HF and graft-related immune activation.