Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation

Irritable bowel syndrome (IBS) is often accompanied by extra-intestinal symptoms, including fatigue and musculoskeletal pain. The present study aimed to investigate whether these symptoms were associated with markers of enterocyte disintegrity, endotoxemia and inflammation. Patients with IBS were recruited consecutively from our outpatient clinic (n=94) and compared with a group of healthy controls (n=20). Habitual symptoms were assessed using the IBS Severity Scoring System, the Fatigue Impact Scale and Visual Analogue Scales for measuring musculoskeletal pain. A lactulose challenge test was performed to induce post-prandial symptoms, and blood samples were obtained prior to and 90 min following lactulose ingestion to determine levels of intestinal fatty acid binding protein (iFABP), lipopolysaccharide (LPS), the LPS co-receptor soluble cluster of differentiation (sCD) 14, monocyte chemoattractant protein-1 (MCP-1) and calprotectin. Habitual symptom scores were high among the included patients, and lactulose ingestion induced significantly more symptoms in the patient group compared with the healthy control group (P=0.0001). Serum levels of iFABP were reduced in IBS patients compared with healthy controls, prior to and following lactulose ingestion (P=0.0002 and P=0.0001, respectively). Following lactulose ingestion, iFABP levels decreased in IBS patients (P=0.0001) and in healthy controls (P=0.02). Fasting levels of LPS, sCD14, MCP-1 and calprotectin were not significantly different between IBS patients and healthy controls. However, following lactulose ingestion, LPS levels increased in healthy controls (P=0.03), whereas MCP-1 levels decreased in IBS patients (P=0.008). Intestinal and extra-intestinal symptom severities were not correlated with levels of circulating biomarkers. No assessed biomarker in the present study appeared to be associated with symptom development in IBS patients. However, the implications of the low levels of iFABP observed require further investigation.