Morphological and regional spontaneous functional aberrations in the brain associated with Crohn's disease: a systematic review and coordinate-based meta-analyses.

Crohn's disease is an acknowledged "brain-gut" disorder with unclear physiopathology. This study aims to identify potential neuroimaging biomarkers of Crohn's disease. Gray matter volume, cortical thickness, amplitude of low-frequency fluctuations, and regional homogeneity were selected as indices of interest and subjected to analyses using both activation likelihood estimation and seed-based d mapping with permutation of subject images. In comparison to healthy controls, Crohn's disease patients in remission exhibited decreased gray matter volume in the medial frontal gyrus and concurrently increased regional homogeneity. Furthermore, gray matter volume reduction in the medial superior frontal gyrus and anterior cingulate/paracingulate gyri, decreased regional homogeneity in the median cingulate/paracingulate gyri, superior frontal gyrus, paracentral lobule, and insula were observed. The gray matter changes of medial frontal gyrus were confirmed through both methods: decreased gray matter volume of medial frontal gyrus and medial superior frontal gyrus were identified by activation likelihood estimation and seed-based d mapping with permutation of subject images, respectively. The meta-regression analyses showed a positive correlation between regional homogeneity alterations and patient age in the supplementary motor area and a negative correlation between gray matter volume changes and patients' anxiety scores in the medial superior frontal gyrus. These anomalies may be associated with clinical manifestations including abdominal pain, psychiatric disorders, and possibly reflective of compensatory mechanisms.

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.

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.

Decreased Gray Matter Volume in the Frontal Cortex of Migraine Patients with Associated Functional Connectivity Alterations: A VBM and rs-FC Study.

BACKGROUND: Resting-state functional MRI is widely used in migraine research. However, the pathophysiology and imaging markers specific for migraine pathologies are not well understood. In this study, we combined both structural and functional images to explore the concurrence and process of migraines. METHODS: Thirty-four patients with a history of migraine without aura presenting during the interictal period (MwoA-DI), 10 patients with migraine without aura presenting during the acute attack (MwoA-DA), and 32 healthy controls (HCs) were recruited in this study. All participants underwent scanning via MRI. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to detect the brain structural and associated brain functional connectivity. RESULTS: In VBM analysis, a decrease of gray matter volume (GMV) in the middle frontal cortex was found in MwoA patients compared with HCs. The GMV of the middle frontal cortex had a negative correction with the duration of disease. In rs-FC analysis, the left middle frontal cortex (lower, VBM result) in both the MwoA-DA and the HC groups showed significantly increased functional connectivity with the left middle frontal cortex (upper) and left superior frontal cortex compared with MwoA-DI. The left middle frontal cortex (lower) in the MwoA-DI group also showed decreased functional connectivity in the left posterior cingulate cortex (PCC) compared with the HC group. The left middle frontal cortex (lower) in the MwoA-DA group demonstrated significantly increased functional connectivity in the left cerebellum lobule VI compared with the HC group. CONCLUSIONS: Our results demonstrated that the middle frontal cortex may serve as an important target in the frequency and severity of migraines due to its role in pain regulation through the default mode network, especially in the PCC. In addition, the cerebellum may modulate the pathophysiology of migraines by serving as a communication point between the cortex and the brainstem.

Electroacupuncture Attenuated Anxiety and Depression-Like Behavior via Inhibition of Hippocampal Inflammatory Response and Metabolic Disorders in TNBS-Induced IBD Rats.

This study was designed to explore the potential mechanisms of electroacupuncture (EA) in treating inflammatory bowel disease- (IBD-) related anxiety and mood disorders. A colitis model was induced in rats with 2, 4, 6-trinitrohydrosulfonic acid (TNBS), followed by ST36 and SP6 targeted therapy by EA or sham EA treatment. The elevated plus maze (EPM) and open-field test (OFT) were performed to assess the state of anxiety and depression-like behavior. Tests were carried out by 16S rDNA amplification sequence, 1H nuclear magnetic resonance (1H NMR) spectroscopy, immunofluorescence staining, and enzyme-linked immunosorbent assay (ELISA). The analyses detailed metabolic alterations and the Toll-like receptor 4 (TLR4) signaling pathway/NOD-like receptor protein 3 (NLRP3) inflammasome in rats' hippocampal region. Furthermore, the activity of the hypothalamic-pituitary adrenal (HPA) axis and gut microbiome was assessed. As a result of treatment, EA significantly improved in the behavioral tests and altered the composition of the gut microbiome through a significant increase in the density of short chain fatty acids (SCFAs) producers mainly including Ruminococcaceae, Phascolarctobacterium, and Akkermansiaceae. EA upregulated the metabolites of the hippocampus mainly containing l-glutamine and gamma-aminobutyric acid (GABA), as well as ZO-1 expression. Whereas the treatment blocked the TLR4/nuclear factor- kappa B (NF-κB) signaling pathways and NLRP3 inflammasomes, along with downregulating the interleukin- (IL-) 1ß level. The hyperactivity of the HPA axis was also diminished. In conclusion, EA at ST36 and SP6 attenuated anxiety and depression-like behavior in colitis model rats through their effects on the gut microbiome by modulating the hippocampal inflammatory response and metabolic disorders, as well as the HPA axis. This study provides evidence for clinical application of EA to serve as an adjunctive treatment for IBD-related anxiety and depression.

1H NMR combined with chemometrics for the rapid detection of adulteration in camellia oils.

Proton nuclear magnetic resonance (1H NMR) and chemometrics were employed to detect the adulteration of camellia oil (CAO) with 3 different cheap vegetable oils. With the intensity of 15 selected 1H NMR signals as input variables, principal component analysis (PCA) showed good group clustering results for pure and nonpure CAO, but unsatisfied identification accuracy for the adulterated oil types, indicating relatively small difference among those oils. Whereas these difference could be revealed by orthogonal projection to latent structures discriminant analysis (OPLS-DA), with identification accuracy higher than 90%. Partial least squares (PLS) was further applied for the prediction of adulteration level in CAO. With less than 6 variables screened out by variable importance in the projection (VIP) scores as potential key markers, the developed PLS models showed better accuracy. The prediction results for 10 hold-out samples also confirmed that this method was accurate and fast for the detection of CAO adulteration.