I-FABP, citrulline and non-invasive liver dysfunction indices in patients with depression – cross-sectional study results

TL;DR

The study explores how gut and liver health are linked in people with depression, finding that gut markers like I-FABP and citrulline are associated with liver dysfunction indicators.

Contribution

This study is the first to investigate the relationship between intestinal dysfunction biomarkers and non-invasive liver indices in depression patients, considering MetS and lifestyle factors.

Findings

Higher I-FABP and I-FABP/CIT ratio were observed in individuals with elevated Fibrosis-4 Index.

Vegetable and seed consumption, citrulline levels, waist circumference, and quality of life predicted liver fibrosis risk.

Participants with liver dysfunction but no MetS had higher citrulline levels, suggesting better gut integrity.

Abstract

Dysfunction of the intestinal epithelial barrier, often observed in individuals with depression and Metabolic Syndrome (MetS), may contribute to liver dysfunction and increased cardiovascular risk (CVR). However, hepatic alterations influenced by enteric dysfunction in individuals with depression remain insufficiently investigated. The aim of the study is to investigate the associations between the non-invasive indices of hepatic steatosis and fibrosis and intestinal dysfunction biomarkers in patients with depressive disorders, taking into account the presence of MetS or its components, as well as dietary, behavioral and psychosocial factors, and antidepressant intake status.

In this cross-sectional study, data from 116 subjects were analyzed. The intestinal function blood biomarker citrulline (CIT) and gut permeability indicator Intestinal Fatty-Acid Binding Protein (I-FABP) were assessed alongside non-invasive liver-related parameters. Metabolic, dietary, and psychometric parameters were also evaluated.

Median I-FABP and I-FABP/CIT ratio values were higher in individuals with Fibrosis-4 (FIB-4) Index > 1.3 than in those with FIB-4 < 1.3 (p = 0.027 and rrb=0.447; p = 0.018 and rrb=0.479, respectively). In a logistic regression model with FIB-4 > 1.3 as the dependent variable, vegetable and seed consumption, CIT levels, waist circumference (WC) and quality of life were significant predictors, with WC being the most crucial (p = 0.019, OR = 1.1; 95% CI: 1.017-1.205). Additionally, subjects with Hepatic Steatosis Index (HSI) > 36.0 who did not have concomitant MetS had higher CIT levels compared to those meeting both criteria (p = 0.016, rrb=0.529).

The association between FIB-4 and I-FABP seems to reflect an increased risk of hepatic abnormalities and related CVR in individuals with depression, particularly those with suspected intestinal permeability disturbances, with CIT serving as a significant predictor.. Reduced CIT levels in participants with MetS and liver dysfunction suggest greater impairment of gut integrity than in liver dysfunction alone. Conversely, individuals with liver dysfunction, in the absence of MetS, may have preserved intestinal function, as indicated by higher CIT concentrations.

Trial was registered with the ClinicalTrials.gov registry (ClinicalTrials.gov ID: NCT04756544, https://clinicaltrials.gov/study/NCT04756544, registration date: 11/02/2021).

The online version contains supplementary material available at 10.1186/s12876-025-04559-7.

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