Background and aimAwareness of eosinophilic esophagitis (EoE) has gradually increased in Japan, therefore the characteristics of this disease in the Japanese patient population need to be elucidated. This study aimed to investigate the features of EoE in the Japanese population.MethodsDuring a 2-year period, all gastrointestinal endoscopies were performed with maximum attention being paid to identify EoE through endoscopic findings. Clinical features and findings were analyzed among this population.ResultsAmong a total of 8589 patients (general gastrointestinal endoscopy, performed for evaluation of symptoms or disease follow-up: 3669; medical check-up endoscopy, routinely performed in asymptomatic patients: 4920), 17 patients (0.20%) were diagnosed with esophageal eosinophilia (mean age ± standard deviation: 44±11.9 years; 1 female). Only 6 patients with esophageal eosinophilia were diagnosed by general gastrointestinal endoscopy; among them, 3 patients had dysphagia and 3 were asymptomatic. The remaining 11 patients were diagnosed by medical check-up endoscopy. All patients were treated with a proton pump inhibitor (PPI); 5 were diagnosed with EoE and 12 with PPI responsive esophageal eosinophilia. Chronological endoscopy analysis showed that EoE findings could be observed for a mean of 6.1 years prior to diagnosis, and the disease did not significantly progress in severity.ConclusionsMost Japanese patients with EoE have mild and slowly progressing disease, which can be diagnosed when close attention is paid to the endoscopic findings. Medical check-up endoscopy in Japan could be a great opportunity for the early diagnosis of EoE.

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

Background The correlation of the growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) with non‐alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter‐organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH‐releasing hormone and IGF‐1, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD. Methods The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF‐1 were examined in NAFLD models of choline‐deficient defined l‐amino‐acid diet‐fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach. Key Results The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF‐1 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits. Conclusions Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF‐1 from the liver.

EoGE is a unique disorder with a variable clinical course. Although further studies are required to confirm our observations, the presence of other allergic disorders is associated with chronicity or multiple flares. Peripheral eosinophil level may be an effective biomarker for recurrence in patients with severe systemic disorders at diagnosis.