Background and Aim: Curcumin may have promising application in the prevention and amelioration of inflammatory bowel disease (IBD). However, the underlying mechanisms underpinning the ability of curcumin to interact with the gut and liver in IBD remains to be defined, which is the exploration aim of this study. Methods: Mice with dextran sulfate sodium salt (DSS)-induced acute colitis were treated either with 100 mg/kg of curcumin or phosphate buffer saline (PBS). Hematoxylin-eosin (HE) staining, 16S rDNA Miseq sequencing, proton nuclear magnetic resonance ( 1 H NMR) spectroscopy, and liquid chromatography-tandem mass spectrometry (LC-MS/ MS) were applied for analysis. Spearman's correlation coefficient (SCC) was utilized to assess the correlation between the modification of intestinal bacteria and hepatic metabolite parameters. Results: Curcumin supplementation not only prevented further loss of body weight and colon length in IBD mice but also improved diseases activity index (DAI), colonic mucosal injury, and inflammatory infiltration. Meanwhile, curcumin restored the composition of the gut microbiota, significantly increased Akkermansia, Muribaculaceae_unclassified, and Muribaculum, and significantly elevated the concentration of propionate, butyrate, glycine, tryptophan, and betaine in the intestine. For hepatic metabolic disturbances, curcumin intervention altered 14 metabolites, including anthranilic acid and 8-amino-7oxononanoate while enriching pathways related to the metabolism of bile acids, glucagon, amino acids, biotin, and butanoate. Furthermore, SCC analysis revealed a potential correlation between the upregulation of intestinal probiotics and alterations in liver metabolites. Conclusion:The therapeutic mechanism of curcumin against IBD mice occurs by improving intestinal dysbiosis and liver metabolism disorders, thus contributing to the stabilization of the gut-liver axis.

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.

Anxiety and depression caused by inflammatory bowel diseases (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. This study unveiled promising evidence that choline dysfunction may be a cause of IBD induced mood disorders. Analysing Dextran Sulfate Sodium Salt (DSS)-induced IBD mice model with transcriptomics and metabolomics technology, it was discovered that mRNA responsible for acetylcholine synthesis and secretion were increased and the phosphatidylcholine (PC) content were decreased in prefrontal cortex (PFC) of IBD mice compared to the Control. Fecal Metagenomics showed that the microbiome and lipid metabolism were also abnormal in IBD mice. Since both acetylcholine and PC are choline metabolites, we inferred that the IBD mice may suffer from choline deficiency and choline metabolism disorder. Following supplementation of CDP-choline, experimental subjects showed improvements through decreased anxiety-like behaviors, reduced PC degradation and increased acetylcholine synthesis in the PFC. In addition, CDP-choline treatment was shown to restore the gut microbiome and lipid metabolism disorders characteristic of DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a key role in the development and treatment of mood disorders in IBD patients, and choline and its metabolites may play a key role in maintaining the stability of the gut-brain axis.