Increased colonic bile acid (BA) exposure, frequent in diarrhea‐predominant irritable bowel syndrome (IBS‐D), can affect gut function. Nerve growth factor (NGF) is implicated in the development of visceral hyper‐sensitivity (VH). In this study, we tested the hypothesis that BAs cause VH via mucosal mast cell (MMC)‐to‐nociceptor signaling, which involves the farnesoid X receptor (FXR)/NGF/transient receptor potential vanilloid (TRPV)1 axis. BAs were intracolonically administered to rats for 15 d. Visceral sensitivity to colorectal distention and colonic NGF expression were examined. BAs caused VH, an effect that involved MMC‐derived NGF and was accompanied by enhanced TRPV1 expression in the dorsal root ganglia. Anti‐NGF treatment and TRPV1 antagonism inhibited BA‐induced VH. BAs induced NGF mRNA and protein expression and release in cultured mast cells. Colonic supernatants from patients with IBS‐D with elevated colonic BA content transcriptionally induced NGF expression. In FXR−/− mice, visceral sensitivity and colonic NGF expression were unaltered after BA treatment. Pharmacological antagonism and FXR silencing suppressed BA‐induced NGF expression and release in mast cells. Mitogen‐activated protein kinase kinase (MKK) 3/6/p38 MAPK/NF‐κB signaling was mechanistically responsible for FXR‐mediated NGF expression and secretion. The findings show an MMC‐dependent and FXR‐mediated pronociceptive effect of BAs and identify the BA/FXR/NGF/TRPV1 axis as a key player in MMC‐to‐neuron communication during pain processing in IBS.—Li, W.‐T., Luo, Q.‐Q., Wang, B., Chen, X., Yan, X.‐J., Qiu, H.‐Y., Chen, S.‐L. Bile acids induce visceral hypersensitivity via mucosal mast cell–to–nociceptor signaling that involves the farnesoid X receptor/nerve growth factor/transient receptor potential vanilloid 1 axis. FASEB J. 33, 2435–2450 (2019). http://www.fasebj.org

This study was carried out to investigate the effects of tributyrin (TB) on the growth performance, pro-inflammatory cytokines, intestinal morphology, energy status, disaccharidase activity, and antioxidative capacity of broilers challenged with lipopolysaccharide (LPS). A total of 160 one-day-old Cobb broilers were allocated to 1 of 4 treatments, with 4 replicated pens per treatment and 10 birds per pen. The experiment consisted of a 2×2 factorial arrangements of treatments with TB supplementation (0 or 500 mg/kg) and LPS challenge (0 or 500 μg/kg body weight [BW]). On days 22, 24, and 26 of the trial, broilers received an intraperitoneal administration of 500 μg/kg BW LPS or saline. Dietary TB showed no effect on growth performance. However, LPS challenge decreased the average daily gain of broilers from day 22 to day 26 of the trial. Dietary TB supplementation inhibited the increase of interleukin-1β (in the jejunum and ileum), interleukin-6 (in the duodenum and jejunum), and prostaglandin E2 (in the duodenum) of LPS-challenged broilers. Similar inhibitory effects of TB in the activities of total nitric oxide synthase (in the ileum) and inducible nitric oxide synthase (in the jejunum) were also observed in birds challenged with LPS. Additionally, TB supplementation mitigated the decrease of ileal adenosine triphosphate, adenosine diphosphate and total adenine nucleotide and the reduction of jejunal catalase activity induced by LPS. Taken together, these results suggest that the TB supplementation was able to reduce the release of pro-inflammatory cytokines and improve the energy status and anti-oxidative capacity in the small intestine of LPS-challenged broilers.

Background Psychological factors contribute to the pathogenesis of functional dyspepsia (FD). Antidepressant agents are beneficial in treatment of refractory FD. However, their efficacy is greatly hindered by the poor treatment adherence. Stigma is present in patients with chronic diseases or mental disorders and could affect adherence. The present study was aimed to evaluate stigma prevalence in FD patients and to explore the impact of stigma on treatment adherence to antidepressants. Methods Functional dyspepsia patients unsatisfied with the regular first‐line treatment and received newly initiated antidepressant medicine were recruited and subjected to antidepressant treatment for 8 weeks. Stigma scales and symptom scores of dyspepsia, depression, and anxiety were analyzed before and after treatment. Associations between stigma and medication adherence were evaluated. Key results One hundred and ten of the enrolled 138 participants reported minimal disease‐related internalized stigma, and 28 reported mild stigma before antidepressant therapy. Male gender, lower education, and higher scores of dyspepsia, depression, and anxiety were predictors of stigma before treatment. The mean stigma scores increased after 8‐week antidepressant treatment. A proportion (36.4%‐89.9%) of patients showed stigma attached to antidepressant therapy in the 4‐question survey. Post‐treatment stigma scores negatively correlated with treatment adherence and efficacy. Patients with decreased post‐treatment stigma scores displayed better medication adherence and symptom improvement compared to those with elevated or unaltered post‐treatment stigma scores. Conclusions Patients with refractory FD report stigma attached to the disease and antidepressants. It is an obstacle to treatment adherence and efficacy of antidepressant medication in FD therapy.