Abstract
BACKGROUND: Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults. While infections are common, over 50% of patients exhibit autoimmune and immune activation related complications. Chronic inflammation from dysbiosis may affect the heart in CVID, though its relationship with gut barrier and echocardiographic findings is still unclear. This study investigates the associations between intestinal permeability, Trimethylamine N-oxide (TMAO) levels, immune activation, and cardiac function in CVID patients. METHODS: The study included 31 CVID patients and 31 matched healthy controls. Serum zonulin, TMAO, soluble CD14 (sCD14), soluble CD25 (sCD25), Tumor Necrosis Factor-alpha (TNF-α), and IL-17 A levels were measured by ELISA. Cardiac function was assessed using speckle-tracking echocardiography (STE), focusing on global longitudinal strain (GLS). RESULTS: Increased levels of zonulin and TMAO were observed in CVID patients. sCD14 and sCD25 levels correlated strongly with TMAO. TMAO showed a negative correlation with Ejection Fraction and a positive correlation with Pulmonary Artery Pressure (PAP). No significant differences were found in serum TNF-α and IL-17 A levels in the compared groups. Compared to the control group (-19.90 ± 2.41), a remarkable reduction in mean GLS (-18.13 ± 3.13) was determined in the CVID group. These results are early indicators of myocardial dysfunction. Strain analysis showed a significant decrease in negative Apical 4-Chamber View Basal Longitudinal Strain (AP4B) and Apical 3-Chamber View Basal Longitudinal Strain AP3B values in the CVID group (p = 0.012 and p = 0.027). CONCLUSIONS: In this study, elevated serum zonulin and TMAO levels correlated with increased intestinal permeability and immune activation in CVID. High TMAO was linked to early myocardial dysfunction, highlighting the potential of microbiome-targeted therapies and advanced echocardiography for early cardiac risk detection in CVID. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12865-026-00810-2.