Tools and advanced imaging technologies for assessing intestinal epithelial barrier integrity: a systematic review
Year: 2026
Type: review
Study design: Systematic Review
Abstract: The intestinal epithelium is a key component of the intestinal barrier, which is the largest and most complex barrier of the human body, regulating nutrient absorption while restricting the entry of harmful antigens. Breakdown of this barrier facilitates microbial and dietary antigenic translocation, triggering local immune system activation and inflammation. Although barrier alteration alone may not be sufficient to initiate disease, accumulating evidence highlights its critical role in the pathogenesis and progression of a wide range of gastrointestinal and systemic disorders. Early identification of intestinal epithelium and barrier alterations could enable timely therapeutic approaches. This systematic review provides an overview of current in vivo (both noninvasive and invasive) and ex vivo/in vitro approaches used to assess intestinal epithelial barrier alterations. Noninvasive in vivo approaches rely mainly on urinary detection of orally ingested probes, but their clinical utility is limited by lack of standardization and specificity. Circulating and fecal constitutive markers derived from the intestinal barrier, which reflect epithelial alterations, together with indicators of microbial translocation, provide complementary insights but remain insufficiently validated. Advanced invasive endoscopic modalities such as confocal laser endomicroscopy enable near-histological, real-time visualization but are costly and largely used as research tools in specialist centers. In vitro, transepithelial electrical resistance assessment remains the reference standard, though novel technologies (including impedance spectroscopy and organic electrochemical transistors) offer enhanced sensitivity and resolution. Despite progress, major gaps remain, including the absence of a standardized definition of epithelial barrier breakdown, the lack of a practical diagnostic tool, methodological heterogeneity, unvalidated thresholds, and limited prospective validation.
Authors: Sophie Vieujean, Raja Atreya, Andrea Buda, Josselin Caradec, Sandra Citi, Silvio Danese, Olivier Dewit, Matthias Friedrich, Subrata Ghosh, Marietta Iacucci, Vipul Jairath, Arthur Kaser, Rupert W. Leong, Markus F. Neurath, Nicolas Pierre, Mathilde Pohin, Timo Rath, Pauline Rivière, Simon Travis, James Westcott, Sebastian Zeissig, Laurent Peyrin-Biroulet
Institutions: Cliniques Universitaires Saint-Luc, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Hospital of Prato, University of Geneva, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, University of Oxford, University College Cork, Western University, University of Cambridge, Macquarie University, Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, University of Bern, Inserm, Centre Hospitalier Régional et Universitaire de Nancy, Nutrition-Génétique et Exposition aux Risques Environnementaux, Université de Lorraine
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7128727597