Published online Jan 14, 2019. doi: 10.3748/wjg.v25.i2.269
Peer-review started: October 16, 2018
First decision: November 22, 2018
Revised: December 3, 2018
Accepted: December 13, 2018
Article in press: December 13, 2018
Published online: January 14, 2019
Visceral hypersensitivity was considered to be involved in the pathogenesis of irritable bowel syndrome (IBS). Pre-clinical studies have shown that brain-derived neurotrophic factor (BDNF) mediates visceral hypersensitivity via facilitating sensory nerve growth. There have been few studies reporting the intestinal BDNF levels in diarrhea-predominant IBS (IBS-D) patients. And the relationship between BDNF and IBS symptom severity, psychological conditions, visceral sensitivity as well as mucosal nerve fiber density has not been investigated in IBS-D. It could be hypothesized that BDNF may play a role in the pathogenesis of diarrhea-predominant IBS-D.
The main topics of this study included assessing clinical and psychological features and visceral sensitivity, examining BDNF expression and nerve fibres in IBS-D and healthy controls, performing correlation analyses between these parameters, and clarifying whether there were similar mechanisms to that of pre-clinical studies in IBS-D patients. The findings proposed a mechanism by which BDNF may participate in the pathophysiology of IBS-D and may provide new clues for the management of IBS-D.
The present study aimed to measure BDNF expression in the intestinal mucosa of IBS-D patients and to analyze the relationship of BDNF with the clinical and psychological features, visceral sensitivity and nerve fiber density in these patients.
Participants were evaluated for clinical and psychological characteristics using validated questionnaires [IBS Symptom Severity Scale (IBS-SSS), visceral sensitivity index, Hospital Anxiety and Depression Scale (HADS) anxiety Scale and HADS depression Scale]. They also underwent colonoscopy and mucosal biopsy. Visceral sensitivity was tested with a Manoscan 360™ high-resolution manometry system. Mucosal BDNF expression and localization were measured by immunohistochemistry. Mucosal BDNF mRNA levels were quantified using quantitative real-time polymerase chain reaction. Correlation analyses between these parameters were performed. Statistical analyses were performed using SPSS, version 24.0 (SPSS Inc, Chicago, IL, United States).
It was found that IBS-D patients had significantly increased anxiety symptoms and visceral sensitivity, and their mucosal expression of BDNF protein and mRNA and nerve fibers density were significantly elevated. BDNF expression was positively correlated with abdominal pain severity and IBS-SSS score and negatively correlated with visceral sensitivity parameters.
The present study showed evidence that BDNF levels were increased in the intestinal mucosa of IBS-D patients and might be involved in the pathophysiology of IBS-D via facilitating the growth of the nerve fibers in the intestinal mucosa. It also provided some potential clues for more effective treatments in these patients. The authors believe that this study not only contributes to the understanding of the pathophysiology of IBS, but also offers valuable reference for future research and therapies.
This study preliminarily explored the possible role of BDNF involved in the pathogenesis of IBS-D. Future studies should focus on the following aspects. First, the present study only recruited IBS-D patients and the findings could not be generalized to other subtypes. As a result, future research should investigate the possible role of BDNF in the pathophysiology of the other three IBS subtypes. Second, the pathophysiology of post-infectious (PI) and non-PI IBS are different and the two subtypes should be studied separately in the future. Finally, a cause and effect inference could not be made in our study. Therefore, additional well-designed clinical studies on the effect of BDNF on nerve growth, visceral sensitivity and abdominal pain are needed.