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

BackgroundAltered 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. MethodsCRL-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 ResultsTranscriptome 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 & InferencesButyrate-EGC interplay may play a pivotal role in regulation of NGF expression and the development of colonic hypersensitivity in IBS-like animal model.