Vaccination plays a crucial role in safeguarding individuals with inflammatory bowel disease (IBD) from potential epidemics. In light of the resurgence of COVID-19 in China, unvaccinated IBD patients are vulnerable to infection and potentially serious complications. The aim of this study is to assess the vaccination uptake and willingness among IBD patients, as well as to explore the factors influencing their decision to decline vaccination. An online questionnaire was distributed and analyzed. Bivariate analyses and logistic regression models were used to identify relevant factors. Two hundred and three patients from 243 non-vaccinated respondents were included in the analysis. A total of 167 (82.3%) respondents continued to decline vaccination, with individuals holding stable employment and higher family income displaying significantly lower intent (p < .05). The primary factors contributing to their hesitancy were misinformation and apprehension regarding potential side effects. Obtaining vaccine information from online sources, particularly text-based content, and apprehensions surrounding the adverse effects of COVID-19 vaccination were also found to significantly diminish willingness to receive the vaccine (p < .01). The present study revealed that unreliable information about vaccines is a key factor of hesitancy among non-vaccinated IBD patients. Making efforts to spread true information about the COVID-19 vaccine is of great importance.

Iron homeostasis is critical for multiple physiological and pathological processes. DMT1, a core iron transporter, is expressed in almost all cells and organs and altered in response to various conditions, whereas, there is few reviews focusing on DMT1 in diseases associated with aberrant iron metabolism. Based on available knowledge, this review described a full view of DMT1 and summarized the roles of DMT1 and DMT1-mediated iron metabolism in the onset and development of inflammatory and degenerative diseases. This review also provided an overview of DMT1-related treatment in these disorders, highlighting its therapeutic potential in chronic inflammatory and degenerative diseases.

Inflammatory bowel disease (IBD) is a serious chronic condition marked by persistent and recurrent intestinal ulcers. Although the exact cause of IBD remains unclear, it is generally accepted that a complex interaction among dietary factors, gut microbiota, and immune responses in genetically predisposed individuals contributes to its development. Pyroptosis, an inflammatory form of programmed cell death activated by inflammasomes, is marked by the rupture of cell membranes and the subsequent release of inflammatory mediators. Emerging evidence indicates that pyroptosis plays a crucial role in the pathogenesis of IBD. Moderate pyroptosis activation can enhance intestinal immune defenses, while excessive inflammasome activation can trigger an inflammatory cascade, resulting in increased damage to intestinal tissues. This article reviews the molecular mechanisms underlying pyroptosis and highlights its role in the onset and progression of IBD. Furthermore, We explore recent advancements in IBD treatment, focusing on small molecule compounds that specifically target and inhibit pyroptosis.

The probiotic Lactiplantibacillus plantarum (L. plantarum) could ameliorate colitis. Alterations in the composition of gut microbiota (GM) have been proved in cases of colitis. The exopolysaccharides from L. plantarum HMPM2111 (LPE) could be effective in colitis through altering the composition of the GM. These effects were linked to inhibiting intestinal inflammation, regulating the TXNIP/NLRP3 inflammasome axis, and attenuating colonic barrier dysfunction. The combination of fecal microbiota transplantation (FMT) and antibiotic inducement showed that gut bacteria susceptible to vancomycin were inversely associated with colitis features and were necessary for the anti-inflammatory effects of LPE. The elevated abundances of gut commensal Lachnospiraceae bacteria were associated with the restoration of colitis treated by LPE. Metabolomics analysis showed that colitis mice treated with LPE had higher levels of propionate and tryptophan metabolites generated from gut bacteria. The administration of these metabolites protected colitis and resulted in a reduction in inflammatory responses. The outcomes of our investigation emerge the significance of the GM in controlling the protective implications of LPE against colitis. Lachnospiraceae bacteria, together with downstream metabolites, contribute substantially to protection. This work elucidates the essential function of the GM-metabolite axis in producing comprehensive protection versus colitis and identifies prospective treatment targets.

Growing evidence highlights the crucial role of defense mechanisms in the context of chronic diseases. However, few studies have evaluated the impact of these implicit emotion regulation strategies on the adaptation processes related to inflammatory bowel diseases (IBD). This narrative review aimed to explore the role of defense mechanisms in patients with IBD and clarify their association with related psychological and physical symptoms. A literature search was conducted using PubMed and PsycINFO databases to select studies considering defense mechanisms in patients with IBD. Inclusion criteria were English language articles, diagnosis of Crohn's disease or ulcerative colitis, and use of validated assessment instruments specifically related to defense mechanisms. Six studies, including a total of 664 patients, were deemed eligible. Immature defense mechanisms were commonly detected in IBD patients, with significant effects on psychological and physical health. Significant associations were found between defense mechanisms, perceived health-related quality of life (HR-QoL), and psychological distress. Findings suggested that immature defense mechanisms may negatively impact the management of disease, leading to lower perceived HR-QoL, decreased treatment adherence, and increased risk of psychopathological symptoms. Considering these findings, we suggest that an integrated clinical evaluation, including an in-depth investigation of defense mechanisms, may promote more effective psychological treatments and improve psychological well-being in patients suffering from IBD.

Mental disorders are relatively common in individuals who undergo metabolic bariatric surgery (MBS). Prior research suggests that mental disorders may relate to increased healthcare use after MBS. We retrospectively explored the association between preoperative mental health disorders and healthcare use in the first postoperative year.

Patients who underwent primary MBS and had a structured preoperative psychological assessment report were included. Data on healthcare use was collected as the total number of non-routine healthcare appointments including inpatient, outpatient, and emergency department visits. Additionally, gastrointestinal (GI) healthcare use at the radiology, gastroenterology, and emergency departments was analyzed separately.

Of the 944 included patients, 261 (28%) had a preoperatively diagnosed mental disorder. Most prevalent were depressive disorders, anxiety disorders, and eating disorders. Patients with a preoperative mental disorder had a 15% (adjusted, CI 1.04-1.27, p = 0.005) higher rate of total healthcare use compared to those without. Among patients who had any GI-related healthcare, those with a mental disorder had a 61% higher rate of GI-related healthcare use (CI 1.02-2.55, p = 0.041). Patients with a mental disorder tended to have 20% lower odds of having no GI-related healthcare appointments (unadjusted, not statistically significant, CI 0.37-1.74, p = 0.568).

The presence of preoperative mental disorders was weakly related to higher total non-routine hospital healthcare use in the first year after MBS. Models explained only 5-13% of the variation in appointment frequency, meaning unmeasured and/or unknown factors play a role in healthcare use.

The gut-brain axis exemplifies the bidirectional connection between the intestines and the brain, as evidenced by the impact of severe stress on gastrointestinal symptoms including abdominal pain and diarrhea, and conversely, the influence of abdominal discomfort on mood. Clinical observations support the notion of the gut-brain connection, including an increased prevalence of inflammatory bowel disease (IBD) in patients with depression and anxiety, as well as the association of changes in the gut microbiota with neurological disorders such as multiple sclerosis, Parkinson's disease, stroke and Alzheimer's disease. The gut and brain communicate via complex mechanisms involving inflammatory cytokines, immune cells, autonomic nerves, and gut microbiota, which contribute to the pathogenesis in certain gut and brain diseases. Two primary pathways mediate the bidirectional information exchange between the intestinal tract and the brain: signal transduction through bloodstream factors, such as bacterial metabolites and inflammatory cytokines, and neural pathways, such as neurotransmitters and inflammatory cytokines within the autonomic nervous system through the interaction between the nerve cells and beyond. In recent years, the basic mechanisms of the pathophysiology of the gut-brain axis have been gradually elucidated. Beyond the gut-brain interaction, emerging evidence suggests the influence of the gut extends to other organs, such as the liver and lungs, through intricate inter-organ communication pathways. An increasing number of reports on this clinical and basic cross-organ interactions underscore the potential for better understanding and novel therapeutic strategies targeting inter-organs networks. Further clarification of interactions between multiorgans premises transformative insights into cross-organ therapeutic strategies.

Primary Care is the first point of contact for most patients after the onset of symptoms of inflammatory bowel disease (IBD). Establishing an initial diagnostic process based on compatible symptoms and agreed criteria and referral pathways, depending on the degree of suspicion and the patient's situation, can reduce diagnostic delays. Once the patient is referred to the Digestive specialist and the diagnosis of IBD is established, a treatment and follow-up plan is structured. The management of the patient must be shared with the participation of the family practitioners in the diagnosis and treatment of concomitant or intercurrent pathologies, the recognition of flare-ups or complications (of IBD or treatments), education tasks or adherence control. With the purpose of developing a comprehensive guide on the management of IBD aimed at Primary Care doctors, we have developed this positioning document collaboratively between the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU).

Psychological stress is widely recognized as a key factor that can initiate or aggravate symptoms in patients with inflammatory bowel disease (IBD). This research was aimed at examining the influence of stressors, coping mechanisms and psychological symptoms on disease activity in patients with Crohn's disease (CD) and ulcerative colitis (UC).

A retrospective case-control research was performed with 138 patients diagnosed with IBD (76 with CD and 62 with UC). The participants were categorized into case groups (active disease: 31 CD, 38 UC) and control groups (inactive disease: 31 CD, 38 UC), with matching on demographic and clinical characteristics. Each participant completed several assessments such as the Simple Clinical Colitis Activity Index (SCCAI), the Harvey-Bradshaw index (HBI), the Life Distress Inventory (LDI), the Symptom Checklist (SCL-25) and the Coping Inventory for Stressful Situations (CISS-21).

Participants experiencing active disease reported higher levels of life stress, with mean scores of 65.42 ± 8.88 in CD and 65.42 ± 8.88 in UC, in comparison with 45.97 ± 13.23 and 41.79 ± 13.49, respectively, in those with inactive disease. Additionally, psychological symptoms were more prevalent in both CD group (57.00 ± 12.71 vs. 47.39 ± 14.65) and the UC group (57.80 ± 9.82 vs. 40.05 ± 11.23) with active disease. Patients with active disease were more likely to employ coping strategies centered on avoidance, emotional responses and tasks than those without disease activity. Logistic regression analysis identified life stress (p < 0.001, 95% CI = [1.06-1.18], B = 1.24) and emotion-focused coping strategies (p < 0.001, 95% CI = [1.26-1.88], B = 1.54) as notable predictors of disease activity, whereas task-focused coping emerged as a protective factor (p < 0.029, 95% CI = [1.68-1.98], B = 1.81).

This research underscores the critical role of managing stress and adopting effective coping mechanisms in reducing the likelihood of disease flare-ups in IBD subjects. Healthcare providers should prioritize integrating these approaches into treatment protocols for IBD management.

Gut microbiota imbalance-induced inflammatory response and oxidative stress are two of the main reasons causing ulcerative colitis (UC). Probiotics show potent modulating effects on microbiota imbalance and have been considered as an optimal substitute of antibiotics for preventing UC. However, the harsh environment of the gastrointestinal tract is not conducive to the survival and persistence of probiotics. Herein, we developed an efficient surface coating strategy to overcome the delivery challenges of probiotics and also endow them with multiple functions through layer-by-layer coating with tannic acid (TA)-Mg2+ and casein phosphopeptide (CPP) complexes. Saccharomyces boulardii (SB), one of yeasts that have been widely applied in the food and pharmaceutical field, was used as a model probiotic for assessing the synergistic effects of this coating strategy on preventing UC. Multi-functionalized probiotic thus prepared (called SB@TA-Mg2+@CPP) had significantly enhanced stability under the simulated gastric and intestinal fluid conditions, and also displayed vigorous cell viability and potent antioxidant activity. In the mouse model of dextran sulfate sodium (DSS)-induced colitis, SB@TA-Mg2+@CPP exhibited strong antioxidant and anti-inflammatory effects, remarkably increased the abundance and diversity of gut microbiota, and maintained gut barrier integrity. Meanwhile, SB@TA-Mg2+@CPP notably improved the adsorption of Mg2+, which also contributed to enhance the preventive effect against DSS-induced colitis. In summary, this study provides an efficient coating strategy to develop multi-functionalized probiotics for preventing UC.

Inflammatory bowel disease (IBD), a chronic gastrointestinal disorder, often emerges during childhood and poses significant challenges due to its adverse effects on growth, development, and psychosocial well-being. Circular RNAs (circRNAs) have been implicated in the pathogenesis of diverse diseases. However, the specific biological role and mechanisms of circRNA OMA1 in children with IBD remain largely unexplored. This study investigates the functions and mechanistic pathways of circRNA OMA1 in the progression of IBD. Quantitative real-time PCR (qRT-PCR) was employed to quantify circRNA OMA1 and miR-654-3p expression levels in the serum of children with IBD and in HT-29 cells. Downstream miRNA and mRNA targets of circRNA OMA1 were predicted using StarBase and validated via luciferase reporter assays. An in vitro IBD model was established by treating the human colonic epithelial cell line (HT-29) with 2% dextran sulfate sodium (DSS). Cell viability and apoptosis were assessed using the MTT assay and flow cytometry, respectively. Expression of the apoptosis-related protein cleaved caspase-3 was analyzed via western blotting, and proinflammatory cytokine levels (TNF-α, IL-1β, and IL-6) were measured using ELISA. The expression of circRNA OMA1 was notably lower in the serum of children with IBD and in DSS-treated HT-29 cells than in healthy controls, whereas miR-654-3p expression was upregulated. Bioinformatics analyses revealed a direct interaction between circRNA OMA1 and miR-654-3p. Overexpression of circRNA OMA1 through plasmid transfection increased circRNA OMA1 levels and suppressed miR-654-3p expression in HT-29 cells under both basal and DSS-stimulated conditions. Conversely, transfection with a miR-654-3p mimic reversed these effects. Upregulation of circRNA OMA1 ameliorated DSS-induced injury in HT-29 cells by enhancing cell viability, reducing apoptosis, and downregulating cleaved caspase-3 expression. Moreover, circRNA OMA1 overexpression inhibited the secretion of inflammatory cytokines TNF-α, IL-1β, and IL-6. However, these protective effects were partially reversed by treatment with the miR-654-3p mimic. Additionally, miR-654-3p was shown to directly target RAF1, negatively regulating its expression. The proliferation-promoting and apoptosis-suppressing effects of miR-654-3p inhibitor treatment were mitigated by RAF1-siRNA. Conclusion: Upregulation of circRNA OMA1 alleviates DSS-induced colonic cell apoptosis and inflammation by modulating the miR-654-3p/RAF1 axis. These findings suggest that circRNA OMA1 could be a promising biomarker for the diagnosis and treatment of IBD.

The online version contains supplementary material available at 10.1007/s10616-025-00703-z.

SiniSan (SNS), a traditional formula from the Treatise on Typhoid Fever, has been shown in modern clinical practice to effectively treat both ulcerative colitis (UC) and depression, although the underlying mechanisms remain incompletely understood.

This study employed UPLC-Q-Orbitrap-MS, network pharmacology, molecular docking, and experimental validation to investigate SNS's mechanism in treating UC with comorbid depression.

UPLC-Q-Orbitrap-MS, in conjunction with network pharmacology and molecular docking, identified active constituents and potential targets of SNS. A UC model induced by a 3% dextran sulfate sodium (DSS) solution was used for experimental validation. Therapeutic efficacy was assessed through behavioral tests, ELISA, routine blood tests, histopathology, immunofluorescence, Western blot, and qRT-PCR.

SNS alleviated weight loss and inflammation in DSS-induced colitis in mice while exhibiting antidepressant effects in the open field test, forced swim test, and tail suspension test. Furthermore, SNS improved intestinal mucosal barrier function and restored hippocampal blood-brain barrier integrity. It inhibited microglial proliferation and neuroinflammation in the Hippocampus Cornu Ammonis 1 and dentate gyrus regions. Mechanistic analysis revealed that SNS mediates its effects on UC by modulating targets in the PI3K/AKT signaling pathway.

SNS ameliorates UC with comorbid depression by restoring the integrity of both the intestinal mucosal barrier and the blood-brain barrier, alleviating DSS-induced colitis and neuroinflammation.

Crohn's disease (CD) is a chronic inflammatory condition associated with psychological stress and anxiety. Functional magnetic resonance imaging (fMRI) studies have shown differences in brain function between patients with CD and healthy controls (HC). This study aimed to compare the neural correlates of anxiety inindividuals with CD relative to HC, using resting-state fMRI data.

Participants filled in the State-Trait Anxiety Inventory (STAI), a validated tool for measuring anxiety, and underwent an MRI acquisition, including both structural and functional sequences, to identify brain regions associated with anxiety scores.

Seventeen patients with CD and eighteen HC matched for age, education, and sex participated in the study. No significant group differences emerged in the STAI scores. However, resting-state fMRI analysis revealed distinct patterns of functional connectivity associated with anxiety scores for the two study groups. Among CD group, greater STAI scores correlated with increased functional connectivity, whereas, in HC, they correlated with decreased functional connectivity. Significant clusters were found in brain regions belonging to specific resting-state networks (RSNs): (a) Posterior Cingulate Cortex (PCC, within the Default Mode Network), (b) left Middle Frontal Gyrus (within the Left Fronto-Parietal Network), and (c) PCC and right Superior Temporal Gyrus (within the Dorsal Attention Network).

The differential association between functional connectivity and STAI scores observed for CD and HC participants was located in areas within self-referential (Default Mode Network) and cognitive (Left Fronto-Parietal Network and Dorsal Attention Network) RSNs. Our findings suggest that maladaptive/dysfunctional processing of negative emotions and visceral sensitivity may occur in patients with CD.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.

Background: Depression and anxiety are common in UC patients due to gut microbiota dysbiosis and increased proinflammatory markers. Butyrate, a short-chain fatty acid, participates in the regulation of gut microbiota and inflammation and has neuroprotective effects in neurodegenerative disease. Therefore, we assessed the effects of sodium butyrate supplementation on the disease severity, inflammation, and psychological factors in active UC patients. Methods: This study was a randomized, parallel, double-blind controlled trial. Participants in the intervention (n = 18) and control (n = 18) groups received 600 mg/kg of sodium butyrate or rice starch as a placebo with their main meal, respectively, for 12 weeks. The partial Mayo score was used to evaluate disease severity, while the Westergren method was employed to assess the erythrocyte sedimentation rate (ESR). NLR and PLR were determined using an automated analyzer (XS-500i, Sysmex). Moreover, the psychological factors were assessed by the hospital anxiety depression scale (HADS) and the general health questionnaire (GHQ). Results: In comparison with placebo, sodium-butyrate supplementation significantly decreased the ESR level (-6.66 ± 1.56 vs. 3.00 ± 2.11, p=0.01), NLR (-0.24 ± 0.1 vs. 0.33 ± 0.23, p=0.02), Mayo score (-2.33 ± 0.41 vs. 0.22 ± 0.40, p < 0.001), HADS anxiety score (-2.77 ± 0.64 vs. 0.94 ± 0.63, p=0.001), HADS depression score (-2.38 ± 0.47 vs. 0.61 ± 0.33, p < 0.001), and GHQ total score (-12.11 ± 1.48 vs. 3.55 ± 1.39, p < 0.001). Conclusion: Butyrate could serve as an effective adjuvant treatment for reducing disease severity and alleviating psychological symptoms. This trial was registered on the Research Ethics Committee of Shiraz University of Medical Sciences, with the reference number IR.SUMS.SCHEANUT.REC.1400.037. Trial Registration: Iranian Registry of Clinical Trials: IRCT20211214053401N1.

Ulcerative colitis (UC) is a recurrent intestinal disease caused by a complex of factors, and there are serious adverse effects and tolerance problems associated with the current long-term use of therapeutic drugs. The development of natural food sources and multi-targeted drugs for the treatment of UC is imminent. Portulaca oleracea L. (PO), as a vegetable, has been shown in studies to have an anti-UC effects. However, the relationship between the abundant active ingredients contained in Portulaca oleracea L. and the improvement of intestinal barrier, gut microbiota and metabolites is unclear. In the present study, Portulaca oleracea L. which was found to be rich in phenolic acid-based active ingredients, were effective in alleviating dextran sulfate sodium (DSS)-induced body weight loss, disease activity index (DAI) score and colon length in mice. It also decreased C-reactive protein (CRP) and myeloperoxidase (MPO) responses, reduced the permeation of fluorescein isothiocyanate (FITC)-dextran, lipopolysaccharide (LPS) and evans blue (EB), and improved histopathological scores. Meanwhile, in vitro and in vivo validation revealed the protective effects of purslane on the intestinal barrier indicators ZO-1, Occludin and Claudin-1, and inhibited the expression of inflammation-associated iNOS and NLRP3 proteins through the NF-κB signaling pathway. In addition, purslane increased the diversity of the intestinal flora, enhancing the proportion of the genera Butyricoccus, Dorea and Bifidobacterium and decreasing the percentage of Bacteroides, Turicibacter and Parabacteroides. Serum metabolomics analysis showed that the imbalance of 39 metabolites was significantly reversed after PO deployment. Enrichment analysis showed that Pentose phosphate pathway and Pyruvate metabolism pathway were the key pathways of PO against UC. Overall, purslane effectively improved the intestinal barrier disruption and intestinal inflammation by inhibiting the NF-κB signaling pathway, and adjusted the disorder of gut microbiota and metabolites to exert anti-UC effects.

To investigate the prospective association of frailty status, especially the early stage, with the long-term risk of Gastroesophageal reflux disease (GERD) in a large prospective cohort. We included participants who were free of GERD and cancer at baseline and use of aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) from the UK Biobank (UKB). Frailty status was assessed using Fried phenotype including five items (weight loss, exhaustion, low grip strength, low physical activity, slow walking pace) and classified as non-frail, pre-frail, and frail. The outcome was incident GERD. The frailty status was assessed using Cox proportional hazard model. Among 327,965 participants (mean age 56.6 years) at baseline, 151,689 (46.3%) were pre-frail and 14,288 (4.4%) were frail. During a median of 13.5-years of follow-up, 31,027 (9.5%) participants developed GERD. Compared with non-frail participants, pre-frail (hazard ratios [HR] = 1.21, 95% confidence interval [CI] 1.18-1.24) and frail (HR = 1.60, 95% CI 1.52-1.68) participants had significantly higher risks of GERD. Among the five indicators of frailty, exhaustion demonstrated the strongest association with the risk of GERD (HR = 1.42, 95% CI 1.38-1.47). Subgroup analysis showed strong associations among younger (< 60 years), female, high-educated, unemployed participants, and those who had BMI < 18.5 kg/m2 (all P for interaction < 0.05). Frailty, especially pre-frail, which is potentially reversible, was associated with higher risk of GERD in middle-aged and older individuals. The findings underscore the importance of integrating routine frailty assessments and interventions, especially at the early stage, to improve digestive health.

Ulcerative colitis (UC) is an inflammatory bowel disease influenced by genetic, immune, and environmental factors. This study investigates the link between ferroptosis, a cell death process related to oxidative stress and iron metabolism, and immune infiltration in UC.

We analyzed UC patient transcription data from the Gene Expression Omnibus (GEO) and identified ferroptosis-related genes using FerrDB. Using STRING and Cytoscape, we analyzed protein-protein interactions to identify hub UC Differentially Expressed Genes (UCDEGs) and performed functional enrichment with GO and KEGG pathways. Machine learning helped further identify key UC Differentially Expressed Ferroptosis-related genes (UCDE-FRGs), which were validated using additional GEO datasets and immunohistochemical staining.

A total of 11 hub UCDEGs (CCL2, ICAM1, TLR2, CXCL9, MMP9, CXCL10, IL1B, CXCL8, PTPRC, FCGR3A, and IL1A) and 3 key UCDE-FRGs (DUOX2, LCN2 and IDO1) were identified. GO and KEGG functional enrichment indicates that these genes play a role in immunity and ferroptosis. Analysis of immune cell infiltration showed that there were a large number of Plasma cells, Monocytes, M0/M1 Macrophages and Neutrophils in the UC. Correlation analysis revealed 3 key UCDE-FRGs associated with immune-infiltrated cells in UC. IHC results showed that the expression levels of 3 key UCDE-FRGs in UC were all higher than that in the healthy controls.

In summary, this study identified three key genes related to UC ferroptosis and immunity, namely DUOX2, IDO1 and LCN2. These findings suggest that immune infiltration plays an important role in UC caused by ferroptosis, and that there is mutual regulation between UC and immune-infiltrated cells. Our research revealed the potential application of immune and ferroptosis in the diagnosis, treatment and prognosis of UC, providing new strategies for clinical management.

We aimed to elucidate the function of the mechanosensitive ion channel PIEZO1 in intestinal fibrosis, which is invariably associated with Crohn's disease (CD) and often results in strictures and obstructions, requiring surgical intervention. Notably, PIEZO1 is strongly expressed in fibrotic tissues and linked with fibrotic progression.

Intestinal tissues were procured from 28 patients diagnosed with CD and 8 healthy control subjects. Histological and immunofluorescence assays verified that PIEZO1 is substantially overexpressed in fibrotic intestinal tissues and is involved in epithelial‒mesenchymal transition (EMT). Further gene knockout experiments and transcriptome sequencing elucidated the specific role of PIEZO1 in the pathogenesis of intestinal fibrosis in CD. We generated mice with Piezo1 deletion specifically in intestinal epithelial cells (Piezo1f/f  Vilcre) to validate in vivo that inhibiting Piezo1 function attenuates or reverses intestinal fibrosis associated with CD.

PIEZO1 expression was strongly increased in the fibrotic small intestine of CD patients, thereby promoting EMT and exacerbating intestinal fibrosis. In vivo investigations revealed that the conditional suppression of Piezo1 in intestinal epithelial cells significantly mitigated intestinal fibrosis in dextran sulphate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis model mice. In vitro examinations revealed that Piezo1 expression in intestinal epithelial cells preserved the stability of HIF-1α, induced EMT to stimulate the expression of fibrosis-associated molecules, and promoted fibrosis.

PIEZO1 plays a pivotal role in the regulation of intestinal fibrosis by maintaining the levels of HIF-1α, thereby promoting EMT. Therapeutic strategies targeting PIEZO1 could be used to prevent intestinal fibrosis in CD patients.

Inflammatory bowel disease (IBD) is a chronic condition associated with elevated rates of anxiety and depression and ultimately reduces the quality of life. Thus, preventive care addressing both physical and psychological health is essential. In this study we aimed to explore the protective effects of Indoleacrylic Acid (IA) against lipopolysaccharide (LPS)-induced inflammation using human colorectal adenocarcinoma cells (HT-29) and dextran sulfate sodium (DSS)-induced zebrafish to assess its potential as a novel therapeutic agent for IBD. IA exhibited substantial anti-inflammatory properties in HT-29 cells and zebrafish models. It significantly reduced the production of pro-inflammatory mediators, including PGE2, TNF-α, IL-6, and IL-8, while upregulating MUC2, AhR, and tight junction proteins (ZO-1, occludin, and claudin-1), thereby enhancing mucosal barrier integrity. In zebrafish larvae, IA improved survival rates, boosted mucin production, and reduced macrophage infiltration and heartbeat rate. Behavioral analyses of adult zebrafish revealed that IA alleviated anxiety-like behaviors, as shown by increased locomotion and improved performance in zone preference and light-dark transition tests. By targeting inflammation and anxiety-like symptoms, IA demonstrates a dual benefit by addressing both intestinal inflammation and the psychological burden of IBD. These findings highlight IA's potential as a novel therapeutic agent for managing IBD, offering a comprehensive approach to improving patient outcomes.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with an idiopathic origin, characterized by persistent mucosal inflammation. Anoikis is a programmed cell death mechanism activated during carcinogenesis to eliminate undetected isolated cells from the extracellular matrix. Although existing evidence indicates that anoikis contributes to the modulation of immune response, the involvement of anoikis-related genes (ARGs) in UC pathogenesis and their interaction with infiltrating immune cells has not been thoroughly explored. The GSE75214, GSE92415, and GSE16879 datasets were acquired and integrated from the GEO database. Additionally, 58 ARGs were identified through the GSEA database. Key anoikis-DEGs in UC were identified using three machine learning algorithms, including least absolute shrinkage and selection operator (LASSO) Cox regression, random forest (RF), and support vector machine (SVM). Receiver operating characteristic (ROC) analysis was utilized to evaluate the diagnostic accuracy of each gene. Subsequently, Single sample GSEA (ssGSEA) was executed to explore the relationships within immune cell infiltration, UC subtypes, and key anoikis-DEGs. Besides, unsupervised cluster analysis was conducted to categorize the UC samples into distinct subgroups, followed by comparing subtype differences. Finally, the upstream regulatory network was constructed and visualized. A comprehensive analysis of the involvement of ARGs in UC was performed, revealing their expression profile, correlation with infiltrating immune cells, and enrichment analyses. We identified five key anoikis-DEGs (PDK4, CEACAM6, CFB, CX3CL1, and HLA-DMA) and demonstrated their high diagnostic accuracy for UC. Moreover, CEACAM6, CFB, CX3CL1, and HLA-DMA exhibited positive associations with infiltrating immune cells in UC, whereas PDK4 displayed a negative correlation with all immune cells. Unsupervised cluster analysis enabled the classification of UC patients into two clusters, both of which exhibited distinct gene expression profiles and immune signaling pathways. Further, based upon the upstream regulatory network, TP53, RARB, RXRB, and CTCF potentially exerted regulatory functions. Our analysis identified five key anoikis-DEGs as characteristic biomarkers of UC. These genes were strongly associated with the infiltration of both innate and adaptive immune cells, as well as immune pathways. This study highlights the role of anoikis genes in UC pathophysiology and offers valuable insights for further elucidating UC pathogenesis and individualized therapy.

Primary Care is the first point of contact for most patients after the onset of symptoms of inflammatory bowel disease (IBD). Establishing an initial diagnostic process based on compatible symptoms and agreed criteria and referral pathways, depending on the degree of suspicion and the patient's situation, can reduce diagnostic delays. Once the patient is referred to the Digestive specialist and the diagnosis of IBD is established, a treatment and follow-up plan is structured. The management of the patient must be shared with the participation of the family practitioners in the diagnosis and treatment of concomitant or intercurrent pathologies, the recognition of flare-ups or complications (of IBD or treatments), education tasks or adherence control. With the purpose of developing a comprehensive guide on the management of IBD aimed at Primary Care doctors, we have developed this positioning document collaboratively between the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU).

Inflammatory bowel disease (IBD) is characterized by intestinal mucosal damage that exacerbates inflammation and promotes disease recurrence. Although hydrogel-based therapies have shown potential for mucosal repair, challenges remain due to inadequate targeting and low hydrogel density, leading to ongoing infiltration of harmful substances and delayed mucosal healing. In this study, an inflammation-targeting-triggered healing hydrogel (ITTH hydrogel) is developed, composed of polyvinyl alcohol-alginate microgels (PALMs) and a cyclodextrin polymer crosslinker (CPC). This hydrogel specifically targets inflamed colonic sites and crosslinks in situ to form a dense network. The results demonstrate that the ITTH hydrogel adheres effectively to inflamed colonic tissue in both IBD mouse models and human samples. The dense crosslinked network acts like the mucosal barrier, preventing the penetration of detrimental substances such as bacteria and small molecules, thereby protecting the underlying mucosal tissue. Furthermore, the ITTH hydrogel significantly improved therapeutic outcomes in mice with dextran sulfate sodium (DSS)-induced colitis. These findings suggest that the ITTH hydrogel is a promising candidate for in situ reconstruction of colonic mucosa and the treatment of IBD.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is characterized by symptoms such as fatigue, abdominal pain, and diarrhoea, which may persist even when inflammation is controlled. These symptoms are further exacerbated by psychological stress, which may complicate disease management that involves the gut-brain axis-a bidirectional communication pathway linking the gastrointestinal system and the central nervous system. While stress, anxiety, and depression are prevalent among patients with IBD, access to comprehensive mental health care is often limited, particularly in rural and underserved areas. Virtual reality (VR) has emerged as a promising tool in managing psychological comorbidities and enhancing the overall care of patients with IBD. The integration of VR in IBD care offers a novel, accessible approach to addressing both physical and mental health challenges, potentially improving the quality of life and clinical outcomes for IBD patients. Further research is warranted to evaluate the long-term benefits and broader applicability of VR-based interventions in diverse patient populations.

IBD-Disk is a simple, easy-to-use, and self-administered analogue visual tool for assessing disability in patients with Inflammatory Bowel Disease (IBD). However, it has not yet been validated in Italian. This study aims to validate IBD-Disk in an Italian cross-sectional multicentre study.

This study was conducted in eight IBD centres from February 2023 to October 2023. After forward-backwards translation of IBD-Disk into Italian, patients consecutively completed IBD-Disk (at baseline and after 7 days), IBD-Disability Index (IBD-DI) and IBDQ-32 for quality of life.

We enrolled 767 patients (377, 49,2% CD; 390, 50,8% UC) who completed the IBD-Disk [median score of 30 (IQR=11-52)]. Internal consistency was excellent, with Cronbach's α of 0.92 (95%CI=0.92-0.92). To evaluate the validity, the IBD-Disk was compared with the IBD-DI and IBDQ-32, revealing a significant positive correlation of 0.70 (95% CI=0.66-0.73; p<0.001) and 0.83 (r=0.83, 95% CI=0.80-0.85; p<0.001), respectively. The intraclass correlation coefficient (ICC) was 0.84 (95% CI=0.82-0.86) for test-retest. Female gender, clinically active IBD and the presence of extraintestinal manifestations led to higher IBD-Disk scores.

This study validated the IBD-Disk in a large cohort of Italian IBD patients, demonstrating that it is a valid, reliable and responsive tool for quantifying IBD-related disability. This validation facilitates its integration into the daily clinical management of IBD patients.

Inflammatory bowel disease is a risk factor for brain dysfunction; however, the underlying mechanisms remain largely unknown. In this study, we aimed to explore the potential molecular mechanisms through which intestinal inflammation affects brain function and to verify these mechanisms. Mice were treated with multiple cycles of 1% w/v dextran sulfate sodium (DSS) in drinking water to establish a chronic colitis model. Behavioral tests were conducted using the open field test (OFT), tail suspension test (TST), forced swimming test (FST), and Morris water maze test (MWM). Brain metabolomics, transcriptomics, and proteomics analyses were performed, and key target proteins were verified using qPCR and immunofluorescence. Four cycles of DSS administration induced colitis, anxiety, depression, and spatial memory impairment. The integrated multi-omics characterization of colitis revealed decreased brain chenodeoxycholic acid (CDCA) levels as well as reduced stearoyl-CoA desaturase (Scd1) gene and protein expression. Transplantation of the colitis microbiome resulted in anxiety, depression, impaired spatial memory, reduced CDCA content, decreased Scd1 gene and protein expression, and lower concentrations of monounsaturated fatty acids (MUFAs), palmitoleate (C16:1), and oleate (C18:1) in the brain. In addition, CDCA supplementation improved DSS-induced colitis, alleviated depression and spatial memory impairment, and increased Scd1 gene and protein expression as well as MUFA levels in the brain. The gut microbiome induced by colitis contributes to neurological dysfunction, possibly through the CDCA-Scd1 signaling axis. CDCA supplementation alleviates colitis and depressive behavior, likely by increasing Scd1 expression in the brain.

Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.

The study aims to explore the association between patients diagnosed with inflammatory bowel disease (IBD) in childhood or youth and mental health disorders.

The study is a register-based cohort study of patients with IBD-onset before 25 years of age and matched references. They were followed until 30 years of age. The incidence rate and incidence rate ratio (IRR) for a wide spectrum of mental health disorders were assessed based on diagnostic codes from the Danish National Patient Registry, reimbursed prescriptions for psychotropic medications, and composite measures combining diagnosis and medication. Furthermore, the relative excess risk due to interaction (RERI) for parental educational level and parental mental health disorders were estimated.

A total of 4904 patients with Crohn's disease (CD), 5794 with ulcerative colitis (UC), and 94,802 matched references were identified. Patients with CD-onset before age 18 had a higher risk of anxiety disorders (IRR 1.58 (CI95%: 1.33-1.86)), while patients with CD-onset between age 18 to 24 had a higher risk of both anxiety and mood disorders. Patients with UC-onset before age 18 had a higher risk of anxiety disorders (IRR: 1.39 (CI95%: 1.19-1.64)). In general, patients with IBD had a higher risk of receiving psychotropic medication. Parental education had a subadditive interaction with the risk of emotional disorders for both patients with CD and UC, while maternal mental health disorders had a subadditive interaction for patients with UC.

Patients with CD and UC have a higher risk of mental health disorders, primarily due to an elevated risk of emotional disorders and a higher use of psychotropic medication. Surprisingly, the study demonstrated subadditive effect of parental education and for patients with UC maternal mental health disorders on the risk of emotional disorders.

This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune and rheumatic immune diseases through randomized controlled trials (RCTs).

Two researchers conducted a comprehensive search of Chinese and English databases from their inception until Dec. 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software.

A total of 42 relevant RCTs, involving 2,183 participants, were ultimately included in this study. These RCTs encompassed four types of rheumatic immune and bone diseases, namely rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis, systemic sclerosis arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease, multiple sclerosis, primary Sjögren's syndrome (PSS). The systematic review indicates that MSC transplantation may improve spondyloarthritis, RA, PSS. The meta-analysis reveals that MSC transplantation significantly improved symptoms in patients with OA [VAS (visual analogue scale): bone marrow: SMD = - 0.95, 95% CI - 1.55 to - 0.36, P = 0.002; umbilical cord: SMD = - 1.25, 95% CI - 2.04 to - 0.46, P = 0.002; adipose tissue: SMD = -1.26, 95% CI -1.99 to - 0.52, P = 0.0009)], SLE [Systemic lupus erythematosus disease activity index (SLEDAI): SMD = - 2.32, 95% CI - 3.59 to - 1.06, P = 0.0003], inflammatory bowel disease [clinical efficacy: RR = 2.02, 95% CI 1.53 to 2.67, P < 0.00001]. However, MSC transplantation may not improve the symptoms of multiple sclerosis and systemic sclerosis (Ssc). Importantly, MSC transplantation did not increase the incidence of adverse events (OA: RR = 1.23, 95% CI 0.93 to 1.65, P = 0.15; SLE: RR = 0.83, 95% CI 0.28 to 2.51, P = 0.76; Inflammatory bowel disease: RR = 0.99, 95% CI 0.81 to 1.22, P = 0.96; Multiple sclerosis: RR = 1.12, 95% CI 0.81 to 1.53, P = 0.50), supporting its safety profile across the included studies. These findings suggest that MSC transplantation holds promise for several rheumatic and autoimmune diseases while highlighting areas where further research is warranted.

MSC transplantation may have the potential to treat autoimmune and rheumatic immune diseases. Moreover. MSC transplantation appears to be relatively safe and could be considered as a viable alternative treatment option for autoimmune and rheumatic immune diseases.

Understanding disease burden is imperative for improving inflammatory bowel disease (IBD) management. This real-world survey investigated residual disease burden and treatment satisfaction among European patients with moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD).

The Adelphi Real World IBD Disease Specific Programme was a multinational, cross-sectional survey with retrospective collection of patient- and physician-reported data on disease burden and management. Between October 2020 and March 2021, participating gastroenterologists recruited their next 7 (UC) and 8 (CD) eligible patients and reported demographics and clinical characteristics. Patients completed symptom, health-related quality of life (HRQoL), and treatment satisfaction questionnaires. Data were adjusted for confounding variables and compared between patients in remission (clinical remission, endoscopic remission, or both) and not in remission.

Overall, 1040 patients (UC, n = 502; CD, n = 538) were included. Although most patients were in remission (UC, 66.1%; CD, 69.5%), most still reported symptoms (UC, 63.7%; CD, 74.1%), including flatulence, fatigue/tiredness, and abdominal pain/distension. In UC, there were no significant differences in the likelihood of experiencing 7 of 23 symptoms between patients in remission and not in remission. In CD, there was no significant difference in 19 of 23 symptoms between patients in remission and not in remission. Several symptoms were significantly associated with reduced HRQoL. HRQoL was significantly better among patients in remission than not in remission.

Patients with IBD, both in remission and not in remission, experience residual symptoms that impair HRQoL. Comprehensive endpoints, incorporating HRQoL and patients' perspectives, and improved treatments are needed to address residual disease and patients' needs.

The bidirectional relationship between disease activity and mental health in inflammatory bowel disease (IBD) has prompted investigations into the efficacy of psychotherapies, such as mindfulness-based interventions (MBI), for improving biopsychosocial outcomes. Therefore, the aim is to examine the feasibility, acceptability, and preliminary efficacy of an online-delivered, self-directed MBI, adapted to individuals with IBD and psychological distress, in comparison to wait-list control (WLC).

50 adults with IBD were randomized to WLC (N = 25) or intervention (N = 25) groups. The intervention (MIND4IBD program) consisted of six, weekly, 15-min videos (with guided meditations). Feasibility was examined through recruitment and retention rates, while acceptability was examined through intervention satisfaction ratings and qualitative feedback. Preliminary efficacy was examined using linear mixed models for group differences in outcomes between baseline and post-intervention.

Primary Outcomes. The retention rate for the WLC group was 92 %, while the retention rate for the intervention group was 48 %. However, 16 % of participants allocated to the intervention group never began the intervention, therefore this resulted in a retention rate of 71 % of participants who began the intervention. Acceptability was high with an average intervention satisfaction rating of 83/100.

When compared with the WLC, the MIND4IBD program improved total mindfulness levels (b = 0.29, 95 %CI [0.11,0.47], p = 0.004) with a large effect size (β = 0.54, b = 0.19, 95 %CI [0.04,0.34], p = 0.014). Themes based on participants' intervention feedback included: 1) beginning of journey with mindfulness, 2) the beneficial impact of mindfulness, 3) why adapting the intervention to IBD is important, 4) views on program delivery, and 5) mixed reactions to AI generated presenters.

MIND4IBD is feasible and acceptable for individuals with IBD and psychological distress. Participants' total mindfulness levels increased significantly in the intervention group compared to WLC. Most participants provided positive intervention feedback. These findings warrant a full-scale RCT to determine MIND4IBD's efficacy for IBD.

In patients with inflammatory bowel diseases (IBD), functional complaints frequently persist after the clearing of inflammation and are clinically difficult to distinguish from symptoms of inflammation. In recent years, the influence of bidirectional communication between the gut and brain on gut physiology, emotions, and behavior has been demonstrated.

What mechanisms underlie the development of functional gastrointestinal complaints in patients with irritable bowel syndrome (IBS) and IBD? What therapeutic approaches arise from this?

Narrative review.

The pathogenesis of IBS involves interactions between psychosocial factors, genetics, and microbiota as well as the central and peripheral nervous systems. The interplay between stress and visceral hypersensitivity is of central importance. Therapeutically, lifestyle changes with stress reduction and exercise alongside dietary, pharmacological, and psychotherapeutic options are useful.

The treatment of functional gastrointestinal disorders remains challenging, as pharmacological therapies are often ineffective and gut-directed psychotherapies are rarely available.

Individuals with inflammatory bowel disease (IBD) are at a higher risk of developing mental disorders, such as anxiety and depression. The imbalance between the intestinal microbiota and its host, known as dysbiosis, is one of the factors, disrupting the balance of metabolite production and their signaling pathways, leading to disease progression. A metabolomics approach can help identify the role of gut microbiota in mental disorders associated with IBD by evaluating metabolites and their signaling comprehensively. This narrative review focuses on metabolomics studies that have comprehensively elucidated the altered gut microbial metabolites and their signaling pathways underlying mental disorders in IBD patients. The information was compiled by searching PubMed, Web of Science, Scopus, and Google Scholar from 2005 to 2023. The findings indicated that intestinal microbial dysbiosis in IBD patients leads to mental disorders such as anxiety and depression through disturbances in the metabolism of carbohydrates, sphingolipids, bile acids, neurotransmitters, neuroprotective, inflammatory factors, and amino acids. Furthermore, the reduction in the production of neuroprotective factors and the increase in inflammation observed in these patients can also contribute to the worsening of psychological symptoms. Analyzing the metabolite profile of the patients and comparing it with that of healthy individuals using advanced technologies like metabolomics, aids in the early diagnosis and prevention of mental disorders. This approach allows for the more precise identification of the microbes responsible for metabolite production, enabling the development of tailored dietary and pharmaceutical interventions or targeted manipulation of microbiota.

Aesculus indica is a remarkable species from Sapindaceae family, traditionally used for the treatment of various ailments due to the presence of a variety of bioactive compounds. The present study was planned to evaluate the chemical characterization, anti-inflammatory and antioxidant potential of hydroethanolic extract of A. indica using in vitro and in vivo approaches. A. indica fruit was extracted with a hydroethanolic (70% v/v) solution, filtered, concentrated on a rotary evaporator and crude extract was obtained. In vitro anti-inflammatory potential of A. indica was carried out against peripheral blood mononuclear cells (PBMCs) and a whole blood assay (WBA). Effects of A. indica extracts on proinflammatory cytokines (TNF-α, IFN-gamma, IL-6, IL-1β) and inflammatory mediators (NF-κB, NO and PGE2) concentration in the supernatant of PBMCs and WBA were evaluated using commercial ELISA kits. In vivo anti-inflammatory potential of A. indica hydroethanolic extract was evaluated with carrageenan-induced paw edema in rats. A total of 36 different compounds (mostly phenolics) were detected in A. indica extract with high performance liquid chromatography (HPLC) and UHPCL-QTOF-MS/MS. The extract showed very low cytotoxicity with an IC50 value of 483.68 μg/mL and significantly reduced the levels of proinflammatory cytokines and inflammatory mediators in both PBMCs and WBA models. Furthermore, the extract also effectively inhibited the paw edema by carrageenan in the 2nd hour at 400 mg/kg (73%). Histopathological analysis of rat paw tissue showed significant reduction of cellular infiltration and decrease in swelling of epidermis and dermis by A. indica extracts. The level of enzymatic antioxidants such as superoxide dismutase (SOD) and Catalase (CAT), lipid peroxidation like malondialdehyde (MDA), oxidative stress parameters including total antioxidant status (TAS) and total oxidant status (TOS) and myeloperoxidase (MPO) activity in rat paw tissues were significantly altered after treatment. The combined findings provide evidence that hydroethanolic extract of A. indica is a potential source of bioactive compounds with significant anti-inflammatory and antioxidant activities.

Inflammatory bowel diseases (IBD) are chronic, incurable pathologies with unknown causes, affecting millions of people. Pediatric-onset IBD, starting before the age of 18 years, are increasing, with more aggressive and extensive features than adult-onset IBD. These differences remain largely unexplained. Intestinal mucosal damage, cell death, DNA release from nuclear, mitochondrial, or microbiota sources, and DNA-sensing activating the cGAS-STING pathway may contribute to disease evolution. Increased colonic cGAS and STING are increasingly reported in experimental and human IBD. However, limited knowledge of the mechanisms involved hinders the development of new therapeutic options. Here, we discuss recent advances and unresolved questions regarding DNA release, DNA sensor activation, and the role and therapeutic potential of the cGAS-STING pathway in inflammatory colitis.

Inflammatory bowel disease (IBD) is often accompanied by psychiatric disorders. Emerging evidence suggests that neuroinflammation and oxidative stress contribute to the psychiatric symptoms associated with IBD. Umbelliprenin (UMB) possesses several pharmacological properties, including anti-inflammatory and antioxidant effects. This study aimed to investigate the protective effects of UMB on comorbid behavioral disorders in a mouse model of experimental colitis, focusing on its potential anti-neuroinflammatory and antioxidant activities. After inducing colitis with acetic acid, male NMRI mice were treated for 7 consecutive days with UMB, saline, or dexamethasone. Behavioral assessments included the forced swimming test (FST), splash test, open field test (OFT), and elevated plus maze (EPM). Histopathological changes in the colon were evaluated, and total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and the expression of inflammatory genes (TNFα, IL1β, and TLR4) were measured in the hippocampus. Colitis was associated with increased immobility time in the FST, reduced entries and time spent in the open arms of the EPM, decreased grooming behavior in the splash test, and reduced time spent in the central zone of the OFT. Colitis also resulted in a reduction in TAC and an increase in MDA levels and inflammatory gene expression in the hippocampus. UMB treatment mitigated the behavioral disorders associated with colitis, reduced neuroinflammation and oxidative stress in the hippocampus, and alleviated histopathological alterations in the colon. In conclusion, UMB may reduce behavioral disorders induced by colitis by decreasing oxidative stress and neuroinflammation in the hippocampus.

Scoparone (SCO), also known as 6,7-Dimethoxycoumarin, is a naturally occurring bioactive ingredient originally derived from Chinese herb Artemisiae Scopariae Herba (Yin-Chen-Hao). Previous studies have shown that it is effective in treating some of the liver diseases. Beyond its hepatoprotective effects, an expanding body of research has underscored the immunoregulatory properties of SCO, indicating its potential therapeutic benefits for autoimmune and other inflammatory diseases. Over the past decade, significant advances have been made in understanding the mechanistic insights into its effects on immune-mediated diseases as well as liver diseases. SCO has an impact on various immune cells, including mast cells, monocytes, macrophages, neutrophils and T cells, and affects a broad range of intracellular signaling pathways, including TLR4/Myd88/NFκB, TGFβR/Smad3 and JNK/Sab/SHP-1 etc. Therefore, this review not only summarizes the immunomodulatory and therapeutic effects of SCO on immune-based inflammatory diseases (IMIDs), such as inflammatory bowel disease, osteoarthritis, allergic rhinitis, acute lung injury, type 1 diabetes and neuroinflammatory diseases etc., but also provides a comprehensive summary of its therapeutic effects on hepatic diseases, including non-alcoholic steatohepatitis, fulminant hepatic failure and hepatic fibrosis. In this review, we also include the broad impacts of SCO on intracellular signaling pathways, such as TLR4/Myd88/NFκB, TGFβR/Smad3, Nrf2/P38, JAK2/STAT3 and JNK/Sab/SHP-1 etc. Further researches on SCO may help understand its in-depth mechanisms of action and pave the way for the development of novel drugs to prevent and treat various immune-mediated inflammatory disorders as well as hepatic diseases, thereby significantly advancing its innovations and pharmaceutical applications.

The brain-gut axis constitutes the basis for the bidirectional communication between the central nervous system and the gastrointestinal tract driven by neural, hormonal, metabolic, immunological, and microbial signals. Alterations in the gut microbiome composition as observed in inflammatory bowel diseases can modulate brain function and emerging empirical evidence has indicated that interactions among the brain-gut microbiome-axis seem to play a significant role in the pathogenesis of both inflammatory bowel diseases and psychiatric disorders and their comorbidity. Yet, the immunological and molecular mechanisms underlying the co-occurrence of inflammatory bowel diseases and psychological symptoms are still poorly understood. The aim of this narrative review is to highlight contemporary empirical findings supporting a pivotal role of the gut microbiome in the pathophysiology of highly prevalent neuropsychiatric symptoms in inflammatory bowel diseases such as fatigue, depression, and anxiety. Finally, we focus on microbiome modulation as potential treatment option for comorbid neuropsychiatric symptoms in immune-mediated diseases and especially in inflammatory bowel diseases. High-quality clinical trials are required to clarify how microbiome modulation through dietary interventions or probiotic, prebiotic or synbiotic treatment can be used clinically to improve mental health and thus quality of life of patients with inflammatory bowel diseases.