Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis.

Anxiety and depression caused by inflammatory bowel disease (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis (GBA) mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. Therefore, it's vital to conduct comprehensive research on the GBA in IBD. Multi-omics studies can provide an understanding of the pathological mechanisms of the GBA in the development of IBD, helping to uncover the mechanisms underlying the onset and progression of the disease. Thus, we analyzed the prefrontal cortex (PFC) of Dextran Sulfate Sodium Salt (DSS)-induced IBD mice using transcriptomics and metabolomics. We observed increased mRNA related to acetylcholine synthesis and secretion, along with decreased phosphatidylcholine (PC) levels in the PFC of DSS group compared to the control group. Fecal metagenomics also revealed abnormalities in the microbiome and lipid metabolism in the DSS group. Since both acetylcholine and PC are choline metabolites, we posited that the DSS group may experience choline deficiency and choline metabolism disorders. Subsequently, when we supplemented CDP-choline, IBD mice exhibited improvements, including decreased anxiety-like behaviors, reduced PC degradation, and increased acetylcholine synthesis in the PFC. In addition, administration of CDP-choline can restore imbalances in the gut microbiome and disruptions in lipid metabolism caused by DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a crucial role in the development and treatment of mood disorders in IBD. Choline and its metabolites appear to have a significant role in maintaining the stability of the GBA.

Age- and Sex-Specific MR-Feature Tracking Reference Values of Right Atrial Deformation in Healthy Adults.

BACKGROUND: Although right atrial (RA) myocardial deformation has important implications for patient diagnosis, prognosis, and risk stratification, its implementation in clinical practice has been hampered by limited normal reference values, especially in Asian populations. PURPOSE: To establish age- and sex-specific reference values for RA strain, strain rate (SR), and displacement based on a large sample of healthy Chinese adults using MR-feature tracking (MR-FT). STUDY TYPE: Retrospective. POPULATION: 524 healthy Chinese adults (287 male; mean age 43.7 ± 11.9 years). FIELD STRENGTH/SEQUENCE: 1.5T/balanced steady-state free precession. ASSESSMENT: RA deformation parameters, including reservoir, conduit, and booster strain (εs, εe, and εa), peak positive, early negative, and late negative SR (SRs, SRe, and SRa), and total, passive, and active displacement (Ds, De, and Da), were assessed using MR-FT. STATISTICAL TESTS: Student's t-test, one-way ANOVA, coefficients of determination (r2 ), intraclass correlation coefficients (ICC), and Bland-Altman plots. A P value <0.05 was considered significant. RESULTS: Women demonstrated significantly greater magnitudes of RA deformation parameters than men: εs (57.4% ± 15.1% vs. 44.3% ± 12.6%), εe (37.5% ± 13.4% vs. 27.4% ± 10.9%), εa (19.9% ± 5.7% vs. 16.9% ± 5.0%), SRs (2.62 ± 0.88 sec-1 vs. 2.00 ± 0.63 sec-1 ), SRe (-2.98 ± 1.26 sec-1 vs. -2.16 ± 0.92 sec-1 ), SRa (-2.28 ± 0.75 sec-1 vs. -1.84 ± 0.62 sec-1 ), Ds (-7.80 ± 1.90 mm vs. -7.46 ± 1.70 mm), and De (-4.84 ± 1.31 mm vs. -4.49 ± 1.21 mm). For both sexes, aging was significantly associated with decreased RA reservoir and conduit function (εs, SRs, Ds, εe, SRe, and De), and with increased εa and Da. RA deformation measurements had good to excellent intraobserver and interobserver reproducibility, with ICCs ranging from to 0.790 to 0.972. DATA CONCLUSION: This study provides age- and sex-specific reference values of RA strain, SR, and displacement based on a large cohort of healthy Chinese adults using MR-FT. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

The improvement of intestinal dysbiosis and hepatic metabolic dysfunction in dextran sulfate sodium-induced colitis mice: effects of curcumin.

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-7-oxononanoate 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.

Feasibility and reproducibility of cardiovascular magnetic resonance-feature tracking for quantitative right atrial function in dilated cardiomyopathy patients.

Background: The importance of right heart assessment in dilated cardiomyopathy (DCM) is increasingly recognized. The development of cardiovascular magnetic resonance-feature tracking (CMR-FT) has provided a novel approach to quantify myocardial deformation and evaluate cardiac function. In this study, we aimed to evaluate the feasibility and reproducibility of CMR-FT for the quantitative derivation of right atrial (RA) strain and strain rate (SR) in patients with DCM. Methods: A total of 68 DCM patients (84% male; aged 50.6±13.2 years) and 58 healthy controls (81% male; aged 48.4±11.2 years) were retrospectively enrolled from September 2018 to August 2022 at the First Affiliated Hospital of Zhejiang Chinese Medical University and Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine. RA reservoir, conduit, and booster strain (εs, εe, and εa) and peak positive, peak early negative, and peak late negative SR (SRs, SRe, and SRa) were measured using CMR-FT and compared between 2 groups using Student's t-test. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: Compared to healthy controls, DCM patients showed significantly lower RA strain (εs: 19.7%±9.0% vs. 44.4%±9.7%; εe: 7.9%±5.3% vs. 25.8%±8.6%; εa: 11.8%±6.2% vs. 18.6%±5.1%, all P<0.001) and SR (SRs: 1.17±0.48 vs. 1.92±0.62 s-1; SRe: -0.85±0.56 vs. -1.94±0.63 s-1; SRa: -1.39±0.71 vs. -2.01±0.65 s-1, all P<0.001). There was no significant difference in RA maximum volume index between the 2 groups. Simple linear regression analysis demonstrated a significant correlation between N-terminal B-type natriuretic peptide (NT-proBNP), RA emptying fraction passive (RAEF passive), and RA εe [(NT-proBNP and εe): r=-0.48, P<0.001, 95% confidence interval (CI): -0.64 to -0.26; and (RAEF passive and εe): r=0.41, P=0.001, 95% CI: 0.22 to 0.56, respectively] in DCM patients. Intra- and inter-observer reproducibility was excellent (all ICCs >0.85) for RA deformation measurements. Conclusions: CMR-FT is a promising, noninvasive approach for the quantitative assessment of RA phasic function in patients with DCM. DCM patients exhibit impaired RA reservoir, conduit, and booster pump function prior to visible RA enlargement.

CDP-choline modulates cholinergic signaling and gut microbiota to alleviate DSS-induced inflammatory bowel disease.

Inflammatory bowel diseases (IBD) represent chronic gastrointestinal inflammatory disorders characterized by a complex and underexplored pathogenic mechanism. Previous research has revealed that IBD patients often have a deficiency of choline and its metabolites, including acetylcholine (ACh) and phosphatidylcholine (PC), within the colon. However, a comprehensive study linking these three substances and their mechanistic implications in IBD remains lacking. This study aimed to investigate the efficacy and underlying mechanism of cytidine diphosphate (CDP)-choline (citicoline), an intermediate product of choline metabolism, in a mouse model of IBD induced by dextran sulfate sodium salt (DSS). The results demonstrated that CDP-choline effectively alleviated colonic inflammation and deficiencies in choline, ACh, and PC by increasing the raw material. Further detection showed that CDP-choline also increased the ACh content by altering the expression of high-affinity choline transporter (ChT1) and acetylcholinesterase (AChE) in DSS-induced mice colon. Moreover, CDP-choline increased the expression of alpha7 nicotinic acetylcholine receptor (α7 nAChR) and activated the cholinergic anti-inflammatory pathway (CAP), leading to reduced colon macrophage activation and proinflammatory M1 polarization in IBD mice, thus reducing the levels of TNF-α and IL-6. In addition, CDP-choline reduced intestinal ecological imbalance and increased the content of hexanoic acid in short-chain fatty acids (SCFAs) in mice. In conclusion, this study elucidates the ability of CDP-choline to mitigate DSS-induced colon inflammation by addressing choline and its metabolites deficiencies, activating the CAP, and regulating the composition of the intestinal microbiome and SCFAs content, providing a potential prophylactic and therapeutic approach for IBD.

Electroacupuncture Alleviates 46-Trinitrobenzene Sulfonic Acid-Induced Visceral Pain via the Glutamatergic Pathway in the Prefrontal Cortex.

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.