Background & Aims: Gut dysbiosis and inflammation perpetuates loss of gut-barrier integrity (GBI) and pathological bacterial translocation (BT) in cirrhosis, contributing to infection risk. Little is known about gut inflammation in cirrhosis and how this differs in acute decompensation (AD). We developed a novel approach to characterise intestinal immunopathology by quantifying faecal cytokines (FC) and GBI markers.

Methods: Faeces and plasma were obtained from patients with stable cirrhosis (SC; n=16), AD (n=47), and healthy controls (HC; n=31). A panel of 15 cytokines and GBI markers including intestinal fatty acid-binding protein-2 (FABP2), D-lactate and faecal calprotectin (FCAL) were quantified by electrochemiluminescence/ELISA. Correlations between analytes and clinical metadata with univariate and multivariate analyses were performed.

Results: Faecal (F) IL-1β, IFNγ, TNFα, IL-21, IL-17A/F and IL-22 were significantly elevated in AD vs SC (q<0.01). F-IL-23 was significantly elevated in AD vs HC (p=0.0007). FABP2/D-lactate were significantly increased in faeces in AD vs SC and AD vs HC (p<0.0001) and in plasma (p=0.0004; p=0.011). F-FABP2 correlated most strongly with disease severity (Spearman's rho: Child-Pugh 0.466, p<0.0001; MELD 0.488, p<0.0001). FCAL correlated with plasma IL-21, IL-1β and IL-17F only and none of the faecal analytes. F-cytokines and F-GBI markers were more accurate than plasma in discriminating AD from SC.

Conclusions: FC-profiling represents an innovative approach to investigating the localised intestinal cytokine microenvironment in cirrhosis. These data reveal that AD is associated with a highly inflamed and permeable gut-barrier. FC profiles are very different from the classical innate-like features of systemic inflammation. There is non-specific upregulation of TH1/TH17 effector cytokines and those known to mediate intestinal barrier damage. This prevents mucosal healing in AD and further propagates BT and systemic inflammation.

Original languageEnglish
Pages (from-to)100151
JournalJHEP Reports
Publication statusE-pub ahead of print - 30 Jul 2020


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