Fecal Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for Inflammatory Bowel Disease Original paper

What was studied?

This prospective diagnostic study evaluated fecal-NGAL-biomarker-for-IBD (neutrophil gelatinase–associated lipocalin; also called lipocalin-2) as a noninvasive marker of intestinal inflammation, and directly compared it with the established fecal biomarker calprotectin. Using ELISA-based assays, the investigators measured NGAL in stool and plasma, assessed its stability at room temperature, and tested how well fecal NGAL distinguished active inflammatory bowel disease (IBD) from inactive disease and from key clinical mimics such as irritable bowel syndrome (IBS) and infectious enterocolitis. Biomarker values were correlated with validated clinical activity scores (Partial Mayo for ulcerative colitis [UC] and Harvey–Bradshaw for Crohn’s disease [CD]), endoscopic indices (Mayo endoscopic subscore and SES-CD), and hs-CRP to benchmark performance against both intestinal and systemic inflammation measures.

Who was studied?

Stool testing included 73 patients with IBD (44 UC, 29 CD), 21 with PCR-confirmed infectious enterocolitis (bacterial and viral etiologies), 21 with IBS defined by Rome III criteria and normal colonoscopy, and 23 healthy controls with normal colonoscopy or volunteer status. IBD participants underwent colonoscopy with blinded endoscopic scoring; inactive UC was defined as Mayo ≤1 and inactive CD as SES-CD ≤2 (with specific allowances for non-inflammatory stenosis). Plasma NGAL was measured in a larger, overlapping cohort of 119 IBD patients (65 UC, 54 CD) and 28 healthy controls.

Most important findings

Fecal NGAL (fe-NGAL) was markedly higher in active disease than in inactive IBD, IBS, or healthy controls: active UC median 6.05 mg/kg (IQR 3.6–15.1) and active CD 4.9 mg/kg (1.5–7.7), versus healthy controls 0.3 mg/kg (0.1–0.4) and IBS 0.4 mg/kg (0.2–0.6). Infectious enterocolitis also raised fe-NGAL (median 2.7 mg/kg), reinforcing that it is an inflammation marker rather than IBD-specific. Fe-NGAL correlated strongly with fecal calprotectin overall (Spearman rho 0.82) and tracked endoscopic activity particularly well in UC (rho 0.82 vs Mayo endoscopic score). In ROC analyses, fe-NGAL discriminated active IBD from healthy controls with AUC 0.987 and (at a 0.81 mg/kg cut-off) sensitivity 94.7% and specificity 95.7%, closely matching calprotectin. Importantly for real-world workflows, stool NGAL showed excellent room-temperature stability for up to 7 days, supporting practical sample transport and delayed processing. Tissue staining demonstrated a key biological distinction: NGAL was prominent in inflamed epithelium and granulocytes, whereas calprotectin localized to inflammatory cells without epithelial staining, suggesting NGAL may capture epithelial stress/injury signals that complement neutrophil-derived markers.

Key implications

For microbiome-adjacent clinical practice, fe-NGAL is compelling because NGAL (lipocalin-2) is an iron-sequestering antimicrobial protein that shapes host–microbe competition by limiting bacterial siderophore-mediated iron acquisition, meaning it plausibly reflects host antimicrobial responses to dysbiosis and epithelial barrier perturbation as much as neutrophil influx. Clinically, the study supports fe-NGAL as a robust stool biomarker for diagnosing and monitoring IBD activity with performance comparable to calprotectin, plus a mechanistic rationale for complementary use when epithelial injury is prominent or when neutrophil-based markers are imperfect. However, because fe-NGAL rises in infectious enterocolitis, it should be interpreted alongside clinical context and (when relevant) pathogen testing. Its 7-day room-temperature stability is a pragmatic advantage for outpatient pathways and multicenter sampling.

Citation

Thorsvik S, Damås JK, Granlund AVB, Flo TH, Bergh K, Østvik AE, Sandvik AK. Fecal Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for Inflammatory Bowel Disease. J Gastroenterol Hepatol. 2017. doi:10.1111/jgh.13598