Crossing barriers? Longitudinal evaluation of intestinal permeability in adolescent anorexia nervosa.

Background & aims: Anorexia nervosa (AN) is a severe eating disorder with significant somatic complications, potentially involving an altered intestinal barrier. Prior studies yielded heterogeneous results, ranging from decreased to increased intestinal permeability in AN. This study aimed to assess intestinal permeability in adolescent patients with AN by comparing serum markers Zonulin, Lipopolysaccharide-binding protein (LBP), and intestinal Fatty acid-binding protein (iFABP) with healthy controls (HC) over time.

Methods: We conducted a longitudinal study on 60 female adolescent patients with AN and 36 age-matched HC. Blood samples were collected at admission to inpatient treatment, at discharge, and at a one-year follow-up. Zonulin, LBP, iFABP and inflammation marker Interleukin 6 levels were measured alongside clinical parameters. Linear mixed models were applied to assess group differences and longitudinal changes. Pearson correlations were used to explore clinical associations.

Results: Zonulin levels were significantly decreased in the AN group at admission and again at the follow-up compared to HC. LBP levels were consistently reduced in AN across all three time points. These alterations thus persisted despite weight recovery. No significant differences were observed in iFABP levels between the groups or over time. Zonulin and LBP positively correlated with Interleukin 6, linking gut permeability to inflammatory processes.

Conclusion: Decreased Zonulin and LBP levels suggest reduced paracellular intestinal permeability in adolescent AN while transcellular permeability (iFABP) appears to be rather unaffected. The persistence of these alterations despite weight recovery suggests that reduced intestinal permeability may be a trait rather than a state marker in AN. Our findings challenge the concept of a "leaky gut" in adolescent AN.This highlights the need for further research on the intestinal barrier in AN, while also integrating the role of nutritional intake, gut microbiome interaction and immune reactions, to support the development of gut-targeted therapies.