The Role of Brain-Derived Neurotrophic Factor in Irritable Bowel Syndrome

Abstract

Several studies have implied a role of brain-derived neurotrophic factor (BDNF) in abdominal pain modulation in irritable bowel syndrome (IBS). The aim of this study was to establish BDNF protein expression in human colonic biopsies and to show variation in IBS compared to controls. BDNF protein and mRNA levels were correlated with IBS symptom severity based on the IBS-symptom severity score (IBS-SSS). Biopsies from the descending colon and IBS-SSS were obtained from 10 controls and 20 IBS patients. Total protein of biopsies was extracted and assessed by ELISA and Western Blot. Total mRNA was extracted and gene expression measured by nCounter analysis. In IBS patients, symptom severity scores ranged from 124 to 486 (mean ± sem: 314.2 ± 21.2, >300 represents severe IBS) while controls ranged from 0 to 72 (mean ± sem: 27.7 ± 9.0, <75 represents healthy subjects, p < 0.001). IBS patients reported significantly more food malabsorption, former abdominal surgery and psychiatric comorbidities. BDNF protein was present in all samples and did not differ between IBS and controls or sex. Subgroup analysis showed that female IBS patients expressed significantly more BDNF mRNA compared to male patients (p < 0.05) and male IBS-D patients had higher IBS symptom severity scores and lower BDNF mRNA and protein levels compared to male controls (p < 0.05). Scatter plot showed a significant negative correlation between IBS-SSS and BDNF mRNA levels in the cohort of male IBS-D patients and their male controls (p < 0.05). We detected a high proportion of gastrointestinal surgery in IBS patients and confirmed food intolerances and psychiatric diseases as common comorbidities. Although in a small sample, we demonstrated that BDNF is detectable in human descending colon, with higher BDNF mRNA levels in female IBS patients compared to males and lower mRNA and protein levels in male IBS-D patients compared to male controls. Further research should be directed toward subgroups of IBS since their etiologies might be different.

The Ketogenic Diet Improves Gut–Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems

“…As concerns the neurotrophin, no firm conclusion can be drawn from the literature regarding the levels of the BDNF protein both in the colon of IBS patients and in animal models. Immunohistochemical data suggested increased BDNF mucosal levels in IBS patients [24], whereas Western blot analysis did not show significant differences between patients and controls [26]. From our data on rats, only a slight increase in BDNF protein in the colon could be inferred in the setting of MD-induced IBS.…”

“…BDNF is also an essential neurotrophic factor in the GI tract, where it is synthesized by several cell types, such as enterocytes, neurons, and glial cells [21]. Beyond its neuroprotective and neuroplastic roles, it controls visceral sensation, motility, and intestinal barrier functions [22,23]; thus, along with its cognate tropomyosin-related kinase receptor B (TrkB), it plays a role in hypersensitivity conditions via facilitating sensory nerve growth [24] and its interaction with enteroglial cells [25], although with sex-linked differences [26]. Some studies have been performed in rat models of IBS, showing the effectiveness of the BDNF blockage signaling as a possible therapeutic option for visceral hypersensitivity [27,28].…”

Further Characterization of Intrastriatal Lipopolysaccharide Model of Parkinson’s Disease in C57BL/6 Mice

“…Intrastriatal LPS did not alter the expression of mBDNF and pro-BDNF proteins in the colon. Colonic mBDNF is expressed in epithelial cells and neurons of the myenteric plexus [ 54 ], and it is proposed to be involved in the regulation of colonic motility and visceral hyperalgesia [ 54 ]. Moreover, it has been shown that colonic mBDNF protein is increased in patients with irritable bowel syndrome, and it correlates with disease severity.…”

“…Moreover, it has been shown that colonic mBDNF protein is increased in patients with irritable bowel syndrome, and it correlates with disease severity. Thus, future models of PD with potent gut abnormalities could examine the involvement of colonic mBDNF in the inflammatory processes [ 54 ].…”

Review article: current and future treatment approaches for pain in IBS

“…33 Neurotrophins, especially brain-derived neurotrophic factor (BDNF), play an important role in visceral pain and hypersensitivity. 34 Increased BDNF expression in the colonic mucosa of patients with IBS-D correlated with abdominal pain severity and greater visceral sensitivity. 35 In the central nervous system, abnormal descending noxious inhibitory controls, measured by conditioned pain modulation, are significantly diminished in patients with IBS, 36,37 and the central pain inhibition deficit in IBS reflects interactions between several brain processes related to pain and attention in electrophysiology studies.…”