Title : Precision diagnostics with omics data in IBS and IBD: a clinical case
It is well known the repertoire of gastrointestinal symptoms is limited; so different conditions can present with the same, or similar, symptoms. It follows that the symptoms of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) can overlap. It is widely accepted that differential diagnostics between IBS/IBD usually include several pivotal points with base value of an actual visible mucosal inflammation seen at colonoscopy or cross-sectional imaging and well-accepted biomarkers, such as fecal calprotectin. To date along with these standard methods we can use omics technologies to achieve precision in diagnostics.
A 52 y.o. female patient complained of aching pain in the right iliac region without direct connection with defecation and external causes, bloating and flatulence, type 1 feces (Bristol scale) and mucus secretion with feces, anxiety. The provisional diagnosis was IBS. There were no "anxiety symptoms" in the patient except increasing pain and insufficient clinical effect of spasmolytics.
Routine physical, laboratory and instrumental diagnostic methods were performed in accordance with actual diagnostic guidelines for IBS and endocrine disorders, exocrine pancreatic insufficiency, colon cancer, acute infectious processes with intestinal damage were excluded. The main laboratory findings included elevated CRP (10.6 mg/l) and fecal calprotectin (158.3 mg/g). The X-ray with smart bowel series was performed with evaluation of hyperkinetic dyskinesia of small bowel and chronic enteritis. There was no visible mucosal inflammation in colonoscopy. Histological finding on the bowel biopsy included moderate edema, focal hyperplasia of the papillary epithelium with a large number of goblet cells, moderate fibrosis of the lamina propria with minor hemorrhages, diffuse lymphoplasmacytic infiltration with an admixture of eosinophils. The summation of well-accepted inflammatory biomarkers and histological findings did not allow to reliably establish the diagnosis in the patient.
The metabolome and the most common genetic markers associated with IBD (NOD2 (rs2066844, rs2066845, rs17221417); IL23R (rs2201841); DEFB1(rs11362)) were evaluated. Metabolome analysis included assessment of the profile of short-chain fatty acids (SCFA) and volatile metabolites in feces by GC-MS using Chromatek-Crystal 2000M and Shimadzu QP2010 Ultra with a Shimadzu HS-20 headspace extractor. Analysis of genetic markers revealed mutant genotypes for NOD2 (rs17221417) and IL23R (rs2201841), which significantly increase the risk of Crohn’s disease in the patient. Metabolomic component of the analysis showed the SCFA ratio revealed a tendency for a sharp quantitative and qualitative decrease in butyrate, as well as a change in the ratio of SCFA representation as compared to healthy subjects. The calculated risk index of the diagnostic significance of metabolic profiling were in the "gray zone" and amounted to 73.1 with N up to 100 (index is set up by the Bayes classification model applied for HS-GC/MS data).
Summary of laboratory, endoscopic and histological findings with metabolomics and genomics data allowed to discriminate IBS/IBD and determine a diagnosis of early Crohn’s disease for personalized treatment in this patient.