Assessing intestinal permeability in Crohn’s disease patients using orally administered 52Cr-EDTA Original paper

What was studied?

This original study evaluated 52Cr-EDTA intestinal permeability in Crohn’s disease as a practical, non-radioactive alternative to the classic 51Cr-EDTA permeability test. Crohn’s disease (CD) is tightly linked to impaired epithelial barrier function and gut microbial dysbiosis, yet permeability testing is rarely used clinically because radioactive tracers reduce patient acceptance. The investigators had participants drink a standardized 52Cr-EDTA solution, collect urine for 24 hours, and quantified urinary 52Cr-EDTA (normalized to creatinine) using inductively coupled plasma mass spectrometry (ICP-MS). They then assessed whether measured permeability tracked with inflammatory activity (fecal calprotectin), disease location (Montreal classification), and two hallmark dysbiosis signatures relevant to microbiome databases: reduced Faecalibacterium prausnitzii and increased Enterobacteriaceae.

Who was studied?

Sixty adult CD patients (18–65 years) were recruited from an outpatient inflammatory bowel disease clinic in the Netherlands (March 2016–April 2017). Participants were stratified into low versus increased inflammatory activity using a fecal calprotectin cut-off of 100 μg/g (25 with <100 μg g; 35 with>100 μg/g). Most patients were in clinical remission by the Harvey–Bradshaw Index (median 3), which makes the cohort useful for detecting “subclinical” inflammation signals that might be missed by symptoms alone. Key exclusions were recent antibiotic use (within 3 months), severe clinical activity (HBI >12), and need for induction therapy, limiting confounding by major acute treatment changes or antibiotic-driven microbiome disruption.

Most important findings

Urinary 52Cr-EDTA/creatinine excretion tended to be higher in patients with elevated fecal calprotectin (median ~772 vs ~636 μmol/mol), and—more importantly—showed a statistically significant positive correlation with fecal calprotectin (Spearman ρ = 0.325, P <0.05) even after controlling for key covariates (including sex, disease localization, ileocecal resection, and alcohol intake). This supports permeability as a quantitative, inflammation-linked phenotype in CD rather than a purely “background” abnormality. Disease localization did not produce significant subgroup differences, but patients with purely colonic disease had the highest median excretion, suggesting colonic inflammation or barrier disruption may particularly influence whole-gut 52Cr-EDTA passage in some patients. Microbiome-linked signals were directionally consistent with CD dysbiosis: permeability correlated negatively with F. prausnitzii (ρ = −0.221, P = 0.092) and positively with Enterobacteriaceae (ρ = 0.202, P = 0.126), trends that were not statistically significant but biologically plausible and database-relevant as candidate signatures connecting barrier dysfunction to dysbiosis.

Key implications

Clinically, 52Cr-EDTA testing offers a feasible, non-radioactive permeability assay that aligns with inflammatory burden measured by fecal calprotectin, potentially adding a distinct barrier-focused dimension to noninvasive monitoring in CD. For microbiome signature work, the observed (even if non-significant) coupling of higher permeability with lower F. prausnitzii and higher Enterobacteriaceae supports a mechanistic “barrier–dysbiosis” axis worth capturing: patients with increased permeability may represent a biologically meaningful subgroup for relapse prediction studies, microbiome-targeted interventions, or epithelial-restorative therapies. The study also highlights an important practical point: many patients in symptomatic remission still show wide variation in permeability, reinforcing that barrier integrity can diverge from clinical scores and may reveal subclinical disease activity.

Citation

von Martels JZH, Bourgonje AR, Harmsen HJM, Faber KN, Dijkstra G. Assessing intestinal permeability in Crohn’s disease patients using orally administered 52Cr-EDTA. PLoS One. 2019;14(2):e0211973. doi:10.1371/journal.pone.0211973