X J Xu1,2, Y L Zhang2, L Liu3, L Pan4, S K Yao1,2. 1. Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 2. Gastroenterology Department, China-Japan Friendship Hospital, Beijing, China. 3. Jinan Central Hospital Affiliated to Shandong University, Jinan, China. 4. Immunohistochemistry Laboratory of Clinical Medical Research Institute, China-Japan Friendship Hospital, Beijing, China.
Abstract
BACKGROUND: Neural-immune-endocrine network mechanism has attracted increased attention in diarrhoea-predominant irritable bowel syndrome (IBS-D). Pre-clinical evidence indicates that nerve growth factor (NGF) mediates visceral hypersensitivity and gut barrier dysfunction, via interactions with mast cells and sensory nerve fibres. AIM: To explore the role of nerve growth factor, as well as mast cell-nerve growth factor-nerve interaction in IBS-D pathophysiology. METHODS: In this cross-sectional study, IBS-D patients and healthy controls first underwent clinical and psychological assessments. Visceral sensitivity to rectal distension was tested. As gut barrier function markers, serum diamine oxidase and d-lactate were detected. Rectosigmoid biopsies were taken for the analyses of nerve growth factor expression, mast cell count and activation, and sensory nerve fibres expressing transient receptor potential vanilloid 1 and calcitonin gene-related peptide. Correlations between these parameters were examined in patients. RESULTS: Thirty-eight IBS-D patients (28 males, 10 females; average age 30.2 years) and 20 healthy controls (12 males, 8 females; average age 26.8 years) participated in the study. The patients presented increased psychological symptoms, visceral hypersensitivity and impaired gut barrier function. NGF gene expression, mast cell count and sensory nerve fibres were significantly increased in the patients (P < 0.05). In correlation analysis, NGF expression was positively correlated with the disease severity, anxiety and serum diamine oxidase; visceral sensitivity thresholds were negatively associated with NGF expression (Bonferroni corrected P < 0.0029). CONCLUSIONS: Elevated mucosal NGF may interact with mast cells and sensory nerve fibres, contributing to visceral hypersensitivity and impaired gut barrier function in IBS-D.
BACKGROUND: Neural-immune-endocrine network mechanism has attracted increased attention in diarrhoea-predominant irritable bowel syndrome (IBS-D). Pre-clinical evidence indicates that nerve growth factor (NGF) mediates visceral hypersensitivity and gut barrier dysfunction, via interactions with mast cells and sensory nerve fibres. AIM: To explore the role of nerve growth factor, as well as mast cell-nerve growth factor-nerve interaction in IBS-D pathophysiology. METHODS: In this cross-sectional study, IBS-D patients and healthy controls first underwent clinical and psychological assessments. Visceral sensitivity to rectal distension was tested. As gut barrier function markers, serum diamine oxidase and d-lactate were detected. Rectosigmoid biopsies were taken for the analyses of nerve growth factor expression, mast cell count and activation, and sensory nerve fibres expressing transient receptor potential vanilloid 1 and calcitonin gene-related peptide. Correlations between these parameters were examined in patients. RESULTS: Thirty-eight IBS-D patients (28 males, 10 females; average age 30.2 years) and 20 healthy controls (12 males, 8 females; average age 26.8 years) participated in the study. The patients presented increased psychological symptoms, visceral hypersensitivity and impaired gut barrier function. NGF gene expression, mast cell count and sensory nerve fibres were significantly increased in the patients (P < 0.05). In correlation analysis, NGF expression was positively correlated with the disease severity, anxiety and serum diamine oxidase; visceral sensitivity thresholds were negatively associated with NGF expression (Bonferroni corrected P < 0.0029). CONCLUSIONS: Elevated mucosal NGF may interact with mast cells and sensory nerve fibres, contributing to visceral hypersensitivity and impaired gut barrier function in IBS-D.
Authors: Meenal Singh; Vivekanand Singh; Jennifer V Schurman; Jennifer M Colombo; Craig A Friesen Journal: Sci Rep Date: 2020-07-20 Impact factor: 4.379