Relationship Between Intestinal Permeability to [51Cr]EDTA and Inflammatory Activity in Asymptomatic Patients with Crohn’s Disease Original paper

What was studied?

Intestinal permeability to [51Cr]EDTA as a marker of subclinical inflammation in Crohn’s disease was evaluated by measuring 24-hour urinary excretion after an oral radioactive tracer dose and comparing results with biochemical inflammatory markers and nuclear imaging. Specifically, the investigators tested whether elevated permeability in clinically “quiet” Crohn’s disease reflects an inherited barrier defect or instead signals ongoing, mild intestinal inflammation not captured by routine indices. The protocol used 100 µCi oral [51Cr]EDTA with 24-hour urine collection and defined abnormal permeability as >3.61%/day (97.5th percentile of healthy controls). Inflammation was assessed indirectly via acute-phase reactant proteins (ESR, CRP, α1-acid glycoprotein) and directly via Indium-111 leukocyte scanning in a subset.

Who was studied?

The study included 63 adults with Crohn’s disease (61 unique patients; 2 counted twice because they were tested before and after resection), contributing 162 evaluations over follow-up (most repeated approximately every six months). Patients were stratified into unresected (32 patients; 74 evaluations) and post–ileocolonic resection (31 patients; 88 evaluations) groups, with resected patients further categorized by relapse status. Disease distribution included small bowel only, ileocolonic, or colonic disease, with both sexes represented across groups. A control group of 46 healthy adults established normal permeability ranges and test reproducibility (mean coefficient of variation ~21%).

Most important findings

Across Crohn’s phenotypes, mean urinary [51Cr]EDTA excretion was significantly higher than controls, supporting persistent barrier dysfunction in Crohn’s disease. In unresected patients, abnormal permeability strongly tracked inflammatory activity: sensitivity for detecting biochemical inflammation (via acute-phase reactant proteins) was 97%, though specificity was modest (54%) because many clinically/biochemically “normal” cases still had elevated permeability. Importantly, in the subgroup with normal acute-phase proteins and CDAI <150, every patient with increased permeability had a positive Indium-111 leukocyte scan, indicating mild–moderate intestinal inflammation despite apparent remission. This is the study’s key “subclinical activity” signal: permeability rose when inflammation was present and fell when it resolved within individuals. In resected patients, sensitivity dropped (68%) with similar specificity (~52%), likely due to reduced absorptive surface and faster transit after surgery. Microbiome-relevant interpretation: while no taxa were measured, the work anchors a clinically usable phenotype—increased intestinal permeability in asymptomatic Crohn’s disease behaves like an inflammation-linked host-state marker, which in microbiome signature databases can be modeled as a host barrier/inflammation covariate that often persists even when symptoms and serum markers normalize.

Key implications

For clinicians, “leaky gut” measured by [51Cr]EDTA is not merely a benign residual abnormality in Crohn’s remission; it often indicates ongoing mild–moderate mucosal inflammation that standard blood markers may miss. This suggests permeability testing (or modern non-radioactive surrogates) could help identify patients at risk for relapse or those with treatable subclinical inflammation, especially when symptoms and APRPs are normal. For microbiome-to-clinic translation, the findings reinforce that barrier dysfunction is tightly coupled to inflammatory activity, meaning microbiome signatures linked to Crohn’s remission should be interpreted alongside host permeability/inflammation states; otherwise, “remission” cohorts may be biologically heterogeneous, mixing true quiescence with low-grade inflammatory activity.

Citation

Pironi L, Miglioli M, Ruggeri E, et al. Relationship Between Intestinal Permeability to [51Cr]EDTA and Inflammatory Activity in Asymptomatic Patients with Crohn’s Disease.Digestive Diseases and Sciences. 1990;35(5):582-588