Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review

Abstract

Background and Aim: Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life. Methods: A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both in vivo and in vitro studies were considered. Results: We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17–50%), IBS-D (37–62%) and IBS-C (4–25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies). Conclusions: Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.

Bioactive Compounds in Food as a Current Therapeutic Approach to Maintain a Healthy Intestinal Epithelium

“…The underlying mechanisms are still poorly understood, but several studies have demonstrated, using in vivo and ex vivo approaches, that altered intestinal permeability is associated with low-grade inflammation in all IBS subtypes. The primary mechanisms appear to be related to the regulation of tight and adherent junction proteins, OCLN in particular [ 78 , 79 ]. In a healthy context, OCLN is regulated by phosphorylation, but in IBS-D, it is dephosphorylated, which causes it to be internalized into the cytoplasm [ 78 ].…”

An Update on the Assessment and Management of Pediatric Abdominal Pain

“… 38 Barrier dysfunction has been reported in 37–62% of adults with diarrhea-predominant IBS (IBS-D) and 4–25% of those with constipation-predominant IBS (IBS-C). 39 All four pediatric studies assessing the intestinal barrier in patients with IBS have demonstrated barrier dysfunction, which is associated with abdominal pain, symptom severity, depression, and anxiety. 39 …”

“… 39 All four pediatric studies assessing the intestinal barrier in patients with IBS have demonstrated barrier dysfunction, which is associated with abdominal pain, symptom severity, depression, and anxiety. 39 …”

Treating the Metabolic Syndrome by Fecal Transplantation—Current Status

“…Research on IBS has shown that changes in the microbiome contribute to motility disorders [18][19][20]. Patients with SIBO have different metabolomic profiles [21] as well as higher concentrations of lactate, acetate, and bile acids in comparison with control patients [22].…”