Diagnostic utility of faecal biomarkers in patients with irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder characterized by unspecific symptoms. In clinical practice it is crucial to distinguish between non-inflammatory functional problems and inflammatory, malignant or infectious diseases of the GI tract. Differentiation between these involves the use of clinical, radiological, endoscopic, histological and serological techniques, which are invasive, expensive, time-consuming and/or hindered by inaccuracies arising from subjective components. A range of faecal markers now appears to have the potential to greatly assist in the differentiation of inflammatory bowel disease (IBD) and IBS. Faecal markers of neutrophil influx into the mucosa are reliable indicators of intestinal inflammation and their role has been mainly studied in discriminating IBD from non-IBD conditions (including IBS) rather than organic from non-organic diseases. Phagocyte-specific proteins of the S100 family (S100A12, calprotectin) are amongst the most promising faecal biomarkers of inflammation. Faecal leukocyte degranulation markers (lactoferrin, polymorphonuclear elastase and myeloperoxidase) have also been suggested as diagnostic tools for the differentiation of IBD and IBS. More recently, additional proteins, including granins, defensins and matrix-metalloproteases, have been discussed as differential diagnostic markers in IBD and IBS. In this review, some of the most promising faecal markers, which have the potential to differentiate IBD and IBS and to advance diagnostic practices, will be discussed.

Keywords: Calprotectin; Defensins; Granins; Irritable bowel syndrome; Lactoferrin; M2-pyruvate kinase; Polymorphonuclear elastase; S100A12.

Figure 1

Faecal markers of intestinal inflammation. (1) Initially, unidentified triggers affect the epithelium and lead to an activation of the intestinal immune system; (2) The initiated immune response involves the influx of different innate immune cells (e.g., granulocytes, monocytes, macrophages) and cells of the adaptive immune system (e.g., T cells) into the affected mucosa. These cells actively secret inflammatory mediators or release granule proteins by cell degranulation. The contents of neutrophil granules [ lactoferrin, polymorphonuclear (PMN) elastase, myeloperoxidase (MPO)] have antimicrobial properties. The cytosol is the source of the damage associated molecular pattern proteins S100A8/A9 ( calprotectin) and S100A12 (); (3) During early stages of intestinal inflammation these released proteins spill over from the mucosa into the gut lumen; (4) Some of these factors (including defensins) are also released from the epithelium and the mucus layer; (5) In direct contact with the intestinal mucosa, the faecal stream contains the specific proteins of mucosal disease. The detection of these markers in faeces indicates the presence and degree of intestinal inflammation.

Figure 2

Diagnostic accuracy of faecal markers in the differentiation of organic gastrointestinal disease vs irritable bowel syndrome. The figure illustrates statistical measures of the diagnostic performance of different studies on the role of faecal markers in the diagnosis of irritable bowel syndrome. Sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) of different biomarker studies are represented with highest values close to the center of the “dartboard” (i.e., 100%). Each dot represents a biomarker study and different colors represent the type of the faecal marker (see legend). The size of each dot represents the number of included study subjects (see scale).