Butyrate promotes visceral hypersensitivity in an IBS‐like model via enteric glial cell‐derived nerve growth factor

• Published in: Neurogastroenterology and motility Vol. 30; no. 4; pp. e13227 - n/a
• Main Authors: Long, X., Li, M., Li, L.‐X., Sun, Y.‐Y., Zhang, W.‐X., Zhao, D.‐Y., Li, Y.‐Q.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2018
• Subjects: Colon; EGC; Enteric nervous system; Gene expression; Glial cells; Glial fibrillary acidic protein; Growth factors; Histone deacetylase; Hypersensitivity; IBS; Immunofluorescence; Intestine; Irritable bowel syndrome; Nerve growth factor; NGF; Pain; Rodents; Sodium butyrate; Trichostatin A; visceral hypersensitivity; EGC; sodium butyrate; IBS; NGF; visceral hypersensitivity
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.13227

Background Altered visceral sensation is common in irritable bowel syndrome (IBS) and nerve growth factor (NGF) participates in visceral pain development. Sodium butyrate (NaB) could induce colonic hypersensitivity via peripheral up‐regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an important source of NGF. Whether butyrate could induce visceral hypersensitivity via increased EGC‐derived NGF is still unknown. Methods CRL‐2690 cells were used for transcriptome analyses after butyrate treatment. Rats received butyrate enemas to induce colonic hypersensitivity. Colorectal distention test was performed to assess visceral sensitivity. Immunofluorescence studies were used to evaluate the co‐expression of glial fibrillary acidic protein (GFAP) and NGF or growth associated protein 43 in animal model. NGF expression in rat colon was also investigated. In vitro, CRL‐2690 cells were stimulated with NaB or trichostatin A (TSA). NGF or GFAP expression was also examined. Key Results Transcriptome analyses showed that butyrate induced marked changes of genes expression related to neurotrophic signaling pathways. NaB‐treated rats showed increased visceral sensitivity. An improved NGF expression level was observed in NaB‐treated rats. Meanwhile, a 2.1‐fold increase in co‐expression of GFAP and NGF was also determined in rats received NaB enemas. In cultured cells, both NaB and TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate EGC function via histone deacetylase inhibition. Conclusions & Inferences Butyrate‐EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS‐like animal model. Our study illustrated that butyrate promoted the secretion of NGF from enteric glial cells (EGCs) and contributed to visceral hypersensitivity in rats. The results clarified the potential unignorable source of NGF from EGC and highlighted the important role of EGC in pathogenesis of irritable bowel syndrome (IBS).