Journal of translational gastroenterology最新文献

Imbalanced autonomic function has been reported in gastrointestinal (GI) disorders. The vagus nerve is a major component in the regulation of upper GI motility. Vagal nerve stimulation (VNS) has been shown to improve symptoms of various GI disorders by enhancing parasympathetic activity. This review aims to summarize the clinical efficacy of transcutaneous VNS for GI disorders, focusing on abdominal pain, other GI symptoms, and GI motility, and to discuss the mechanisms of action of transcutaneous VNS. Randomized clinical trials investigating transcutaneous VNS in several major GI disorders, including functional dyspepsia, gastroparesis, constipation, irritable bowel syndrome, and inflammatory bowel disease, were reviewed and discussed. The forms of transcutaneous VNS covered in this review include transcutaneous auricular VNS, transcutaneous cervical VNS, and percutaneous electrical nerve field stimulation. Transcutaneous VNS has been shown to relieve abdominal pain, improve GI symptoms, and accelerate GI motility by enhancing vagal activity in patients with various GI disorders. Transcutaneous VNS is an innovative, effective, and safe therapy for patients with GI disorders; however, large-scale clinical trials are necessary to establish optimal treatment modalities and efficacy.

Background and objectives: Gastrointestinal dysmotility commonly follows thermal injuries, such as burns. This study aimed to investigate the effects and mechanisms of electroacupuncture (EA) on burn-induced gastric dysmotility in rats.

Methods: Sprague-Dawley rats were divided into sham and thermal injury groups subjected to a 60% scald burn. Antagonists, including β-blockade (propranolol), α-blockade (phentolamine), or a selective cyclooxygenase (COX)-2 inhibitor (nimsulide), were administered to verify the pathways involved. Six hours after the burn, the animals were evaluated for gastric emptying and heart rate variability. Blood and gastric tissues were collected for assays of cytokines, hormones, and COX-2 levels. EA was performed at bilateral ST36 (Zusanli) acupoints for 45 m.

Results: Burn injury delayed gastric emptying by 61% (P < 0.01), which was normalized by nimsulide or propranolol but not by phentolamine. EA improved gastric emptying by 87% (P = 0.03) in burned rats. Heart rate variability and plasma hormone (noradrenaline and pancreatic polypeptide) analyses indicated sympathetic hyperactivity in burned rats; EA improved burn-induced sympathovagal imbalance by enhancing vagal activity. Protein and mRNA expressions of COX-2 in the gastric fundus and antrum increased with burn but were normalized by propranolol. EA reduced the burn-induced increase in COX-2 expression in the gastric fundus but not in the antrum. EA also decreased burn-induced elevations in plasma interleukin (IL)-6 and IL-10. Negative correlations were found between gastric emptying and plasma IL-6 levels, as well as between gastric emptying and COX-2 mRNA levels.

Conclusions: These findings suggest that burn-induced gastric dysmotility is mediated via autonomic-COX-2 pathways. EA at acupoint ST36 improves burn-induced delays in gastric emptying by down-regulating COX-2 and pro-inflammatory cytokines through the autonomic nervous pathway.

The brain-gut axis represents a bidirectional communication network that integrates neural, hormonal, and immunological signaling between the central nervous system and the gastrointestinal tract. Adverse childhood experiences (ACEs) have increasingly been recognized for their profound impact on this axis, with implications for both mental and physical health outcomes. This mini-review explores the emerging field of epigenomics-specifically, how epigenetic modifications incurred by ACEs can influence the brain-gut axis and contribute to the pathophysiology of various disorders. We examine the evidence linking epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs to the modulation of gene expression involved in stress responses, neurodevelopment, and immune function-all of which intersect at the brain-gut axis. Additionally, we discuss the emerging potential of the gut microbiome as both a target and mediator of epigenetic changes, further influencing brain-gut communication in the context of ACEs. The methodological and therapeutic challenges posed by these insights are significant. The reversibility of epigenetic marks and the long-term consequences of early life stress require innovative and comprehensive approaches to intervention. This underscores the need for comprehensive strategies encompassing psychosocial, pharmacological, neuromodulation, and lifestyle interventions tailored to address ACEs' individualized and persistent effects. Future directions call for a multi-disciplinary approach and longitudinal studies to uncover the full extent of ACEs' impact on epigenetic regulation and the brain-gut axis, with the goal of developing targeted therapies to mitigate the long-lasting effects on health.

Background and objectives: In this systematic review, we assessed the efficacy, potential mechanisms, and safety of two neuromodulation therapies in patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. The first therapy is vagus nerve stimulation (VNS) utilizing implantable or transcutaneous electrodes, and the second is sacral nerve stimulation (SNS) using implantable or percutaneous electrodes.

Methods: We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed database was comprehensively searched, and studies were rigorously assessed for inclusion and exclusion criteria.

Results: Our analysis encompassed five clinical studies, three on VNS and two on SNS. Most investigated studies demonstrated significant beneficial effects on IBD symptoms, including disease activity, severity of intestinal lesions, and intestinal pain. When evaluating the impact on key IBD pathophysiologies, both VNS and SNS exhibited trends toward reducing biomarkers of intestinal mucosal inflammation and mitigating sympathetic dominance. Importantly, none of the evaluated neuromodulation methods resulted in long-term adverse effects.

Conclusions: Cumulative evidence from the evaluated studies indicates that VNS and SNS therapies effectively alleviate IBD symptoms and may hold promise in addressing the underlying pathophysiologies of IBD, including intestinal mucosal inflammation and sympathetic dominance. Consequently, they represent valuable options for individualized IBD treatment.

Background and objectives: In this systematic review, we evaluated the efficacy, mechanisms and safety of three neuromodulation therapies in patients with gastroesophageal reflux disease (GERD), including the effect of neuromodulation therapies on symptoms and key GERD pathophysiologies, lower esophageal sphincter (LES) pressure, esophageal motility, gastric motility, and parasympathetic activity. The first therapy is LES electrical stimulation using an implantable electrical stimulator, the second is transcutaneous electrical acustimulation, and the third is manual acupuncture.

Methods: A systematic review of literature according to the PRISMA guidelines was performed. Online databases searched include Medline (Ovid), Embase, and PubMed. Studies were assessed for inclusion and exclusion criteria with Covidence, a systematic review software.

Results: The analysis included thirteen clinical studies. Four papers included were registered under two open-label trials on ClinicalTrials.gov for LES electrical stimulation; Five randomized trials with sham-treated controls were analyzed for transcutaneous electrical acustimulation; Four studies, including three involving standard therapy controls and one involving shamtreated controls were included for manual acupuncture. All evaluated studies demonstrated significant beneficial effects on GERD symptoms, using patient-completed questionnaires, objective 24-h measurement of esophageal pH, and patient-reported use of proton pump inhibitors. In evaluating the effect on key GERD pathophysiologies, electrical stimulation significantly increased LES pressure, and transcutaneous electrical acustimulation significantly improved esophageal motility, gastric motility, and parasympathetic activity. None of the evaluated neuromodulation methods produced severe adverse effects.

Conclusions: Cumulative evidence from the evaluated studies indicates that neuromodulation therapies were effective in treating the GERD symptoms and key underlying GERD pathophysiologies. They are thus valuable options for individualized GERD treatment.