Visceral pain caused by inflammatory bowel disease (IBD) greatly diminishes the quality of life in affected patients. Yet, the mechanism of how IBD causes visceral pain is currently not fully understood. Previous studies have suggested that the central nervous system (CNS) and gut-brain axis (GBA) play an important role in IBD-inducing visceral pain. As one of the treatments for IBD, electroacupuncture (EA) has been used to treat various types of pain and gastrointestinal diseases in clinical practice. However, whether EA relieves the visceral pain of IBD through the gut-brain axis has not been confirmed. To verify the relationship between visceral pain and CNS, the following experiments were conducted. 1H-NMR analysis was performed on the prefrontal cortex (PFC) tissue obtained from IBD rat models to determine the link between the metabolites and their role in EA treatment against visceral pain. Western blot assay was employed for detecting the contents of glutamate transporter excitatory amino acid transporters 2 (EAAT2) and the glutamate receptor N-methyl-D-aspartate (NMDA) to verify whether EA treatment can alleviate neurotoxic symptoms induced by abnormal increases of glutamate. Study results showed that the glutamate content was significantly increased in the PFC of TNBS-induced IBD rats. This change was reversed after EA treatment. This process was associated with increased EAAT2 expression and decreased expression of NMDA receptors in the PFC. In addition, an increase in intestinal glutamic-metabolizing bacteria was observed. In conclusion, this study suggests that EA treatment can relieve visceral pain by reducing glutamine toxicity in the PFC, and serves an alternative clinical utility.

Background. The incidence of gastric ulcer (GU) remains high worldwide with limited prevention. While promising animal experiments have suggested a potential preventive role of folic acid (FA) in the development of gastric ulcers, the lack of robust clinical evidence has hindered its widespread implementation as a preventative measure. Therefore, this research aims to determine the relationship between FA supplementation and GU genetically by Mendelian randomization (MR) approach, in order to establish a foundation for developing more effective preventative strategies for this condition. Methods. Genome-wide association studies (GWAS) investigating the association between folic acid or folate supplementation and gastric ulcers were sourced from the UK Biobank. The primary methods for Mendelian randomization analysis were the inverse variance-weighted (IVW) methods, including fixed-effect and random-effect IVW models. Other methods used to test the robustness of the results included simple model and median, weighted model and median, as well as penalized weighted median. Results. MR analysis was performed to investigate the causal effect of FA adjuvant therapy on GU. Seven single nucleotide polymorphisms (SNPs) of genetic loci associated with FA adjuvant therapy were identified. The random-effect and fixed-effect IVW models revealed that genetically predicted FA complementary therapy was significantly related to the reduction of GU risk (OR, 0.870; 95% CI, 0.826–0.917, p < 0.001; OR, 0.870; 95% CI, 0.825–0.918, p < 0.001). Similar results were also observed using simple mode (OR, 0.826; 95% CI, 0.724–0.943, p = 0.030), Weighted mode (OR, 0.828; 95% CI, 0.728–0.941, p = 0.028), simple median method (OR, 0.835; 95% CI, 0.773–0.901, p < 0.001), weighted median (OR, 0.854; 95% CI, 0.794–0.919, p < 0.001) and penalised weighted median (OR, 0.849; 95% CI, 0.789–0.914, p < 0.001). The association between FA supplementary therapy and GU was not considerably driven by any individual SNP according to the leave-one-out sensitivity analysis. Conclusions. This MR study provides evidence from a genetic perspective that FA supplementation may decrease the risk of gastric ulcer. Clinicians should prioritize the role of FA in preventing gastric ulcers among patients.