Clin Res Cardiol (2022).

Intestinal barrier dysfunction, microbial translocation and cytotoxic CD8+ T cell activation in patients with early atrial fibrillation.
J. Friebel1, L. Blöbaum1, M. Witkowski1, K. Jakobs1, M. Puccini1, U. Landmesser1, U. Rauch-Kröhnert1
1CC 11: Med. Klinik für Kardiologie, Charité - Universitätsmedizin Berlin, Berlin;


There is emerging evidence to support a link between inflammation and atrial fibrillation (AF). Activation of T lymphocytes has been linked to the development of atrial myopathy as a structural correlate of AF. Intestinal barrier dysfunction leads to increased microbial translocation. Gutderived serum Lipopolysaccharide (LPS) is associated with enhanced risk of major adverse cardiovascular events in patients with AF. The role of microbial translocation in early AF has not been studied.



We analyzed plasma level (obtained by ELISA) of biomarker that are indicative for intestinal barrier dysfunction (Intestinal fatty-acid-binding Protein, I-FABP; Zonulin; Mucosal vascular addressin cell adhesion molecule 1, MAdCAM-1), microbial translocation (LPS; LPS-binding protein, LBP; soluble CD14, sCD14), atrial structural remodeling (Atrial natriuretic peptide, ANP), as well as cytokines released by cytotoxic CD8+ T cells (granulysin, granzyme B). Our patient cohort consists of 80 patients who presented with a first documented and symptomatic episode of AF. 20 patients with a comparable cardiovascular risk profile (but without atrial fibrillation) served as the control group.



In patients with early AF, elevated plasma levels of I-FABP, MAdCAM-1, and Zonulin indicate increased intestinal mucosal inflammation and barrier disturbance. Furthermore, gut-derived LPS along with higher values of sCD14 and LBP were detected in these patients compared to the control group. Enhanced cytotoxic activity of CD8+ T cells was highlighted by elevated levels of granulysin and granzyme B. CD8+ T cell marker positively correlated with ANP plasma levels (granulysin, p=0,0006 and granzyme B, p=0.0096).



Patients with early AF exhibit higher plasma biomarker indicative for intestinal barrier dysfunction, microbial translocation and cytotoxic CD8+ T cell activation. Inflammation driven via the gut-heart axis might be responsible for the progression of atrial myopathy that later triggers the induction of symptomatic AF.