Vedolizumab is a gut-selective monoclonal anti-α4β7 integrin antibody treatment for Crohn's disease (CD). A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial (NCT03234907) assessed vedolizumab efficacy and safety in Chinese patients with moderate-to-severe CD and inadequate/loss of response/intolerance to previous conventional or anti-tumor necrosis factor-α therapy.

Eligible patients aged ≥18 to ≤80 years with moderate-to-severe CD (CD Activity Index [CDAI] total score 220-400) were randomized 2:1 to vedolizumab 300 mg intravenous infusion or placebo at Weeks 0, 2, 6 of induction, and every 4/8 weeks during Week 14-58 maintenance treatment. Primary and secondary endpoints at Week 10 were enhanced clinical response (≥100-point decrease from baseline CDAI score), and clinical remission (CDAI score ≤150), respectively. Additional Week 10 and/or Week 60 assessments included endoscopic and biomarker (C-reactive protein and fecal calprotectin) measurements.

The study was conducted at 30 centers (August 2017 through August 2020). Enrolled patients (n = 215) were randomized to vedolizumab (n =144) or placebo (n = 71). By Week 10, 19.4% vedolizumab-treated versus 24.3% placebo-treated patients achieved an enhanced clinical response. The Cui-Hung-Wang-adjusted p-value for the primary endpoint was 0.347. After maintenance treatment at Week 60, rates of enhanced clinical response, clinical remission, endoscopic response, mucosal healing, and biomarker improvements appeared greater for vedolizumab-treated than placebo-treated patients.

There were no new safety findings for vedolizumab treatment of Chinese patients with CD. Although the primary endpoint was not met, vedolizumab-treated patients showed improvements in other disease activity measures at Weeks 10 and 60.

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease characterized by progressive mucosal damage. The incidence rate of UC is rising rapidly, which makes the burden of medical resources aggravated. In UC, due to various pathogenic factors such as mucosal immune system disorders, gene mutations and environmental factors disrupting the mucosal barrier function, the midgut pathogenic bacteria and exogenous antigens translocate into the lamina propria, thereby aggravating the inflammatory response and further damages the mucosal barrier. During the progression of UC, Th17 populations that cause inflammation generally increase, while Tregs that suppress Th17 activity decrease. Among them, Th17 mediates immune response, Treg mediates immunosuppression, and the coordinated balance of the two plays a key role in the inflammation and immune process of UC. Natural plant components can regulate biological processes such as immune inflammation from multiple levels of proinflammatory cytokines and signaling pathways. These characteristics have unique advantages and broad prospects in the treatment of UC. In immunomodulation, there is substantial clinical and experimental evidence for the modulatory role of natural plant products in restoring balance between Th17/Treg disturbances in UC. This review summarizes the previous studies on the regulation of Th17/Treg balance in UC by natural plant active ingredients, extracts, and traditional Chinese medicine prescriptions, and provides new evidence for the development and design of lead compounds and natural new drugs for the regulation of Th17/Treg balance in the future, and then provides ideas and evidence for future clinical intervention in the treatment of UC immune disorders and clinical trials.

Inflammatory bowel disease (IBD) induces immunological and autonomic imbalances. Exercise is a beneficial strategy for controlling IBD symptoms. We investigated the role of exercise on gastrointestinal (GI) motility changes and autonomic parameters in rats with ileitis. Rats were divided into control, ileitis, and exercise+ileitis groups. Ileitis was induced by TNBS (40 mM, intraileally). The exercise was swimming (1 h/day/4 weeks, 5%/bw). We assessed eating behaviour and oxidative stress. Body composition was assessed by bioimpedance. Autonomic balance and ECG parameters were measured by an electrocardiogram (ECG). Gastrointestinal motility was evaluated using the phenol red technique. In terms of body composition, total body water (TBW), body mass index (BMI), and fat-free mass (FFM) were higher in the ileitis group (216.80 ± 11.44 mL; 24.09 ± 2.15 g/cm2; 287.1 ± 14.66 g) (p < 0.05) vs. control rats (130.06 ± 28.23 mL; 16.38 ± 2.50 g/cm2; 193 ± 42.21 g) and exercise prevented (91.33 ± 12.33 mL; 11.73 ± 0.47 g/cm2; 133.8 ± 16.82 g) (p < 0.05) these changes. The exercise+ileitis group induces a reduction (p < 0.05) in gastric retention vs. ileitis and control (11.22 ± 1.91% vs. 35.17 ± 1.01% and 33.96 ± 1.77%). Ileitis increased intestinal retention in the duodenum (46.3 ± 2.56% vs. 24.98 ± 1.78%) and jejunum (34.22 ± 2.33% and 34.72 ± 2.83% vs. 47.32 ± 1.48%) (p < 0.05) and decreased intestinal retention in the ileum (p < 0.05) vs. the control group. Exercise+ileitis prevented (p < 0.05) changes in the duodenum (24.96 ± 1.66% vs. 46.3 ± 2.56%) and ileum (40.32 ± 3.75% vs. 14.08 ± 0.88%). Ileitis induces high MDA levels (p < 0.05) vs. control rats (4.43 ± 0.69 vs. 2.15 ± 0.12 nmol/mg of the tissue). This effect was prevented (p < 0.05) in the exercise+ileitis group (2.75 ± 0.21 vs. 4.43 ± 0.69 nmol/mg of the tissue). We observed a reduction in the LF component (p < 0.05) in the ileitis group vs. control group (31.32 ± 3.99 vs. 43.43 ± 3.86). The correlation indicated a stronger interrelationship between the autonomic parameter and intestinal retention in the ileum (r: 0.68; p: 0.04). The current study suggests intestinal ileitis alters GI motility and autonomic balance, and physical exercise can represent an essential non-pharmacological approach to IBD treatment.

Ulcerative colitis is an idiopathic gastrointestinal disease described by chronic inflammation of the digestive system. Cytokines may be responsible for immunopathogenesis, mucosal and tissue damage, and even treatment response. In addition to its role in calcium and phosphorus homeostasis and bone health, vitamin D is an immunomodulatory and anti-inflammatory agent. Understanding the role of cytokines may lead to improving the pathogenesis and treatment of this disease, therefore we aimed to investigate the relative gene expression of pro- and anti-inflammatory cytokines in biopsy samples taken from the affected area in the colon of ulcerative colitis patients and its association with serum vitamin D levels. A total of 47 ulcerative colitis patients were enrolled in this case-control study. The case group consisted of 23 patients with treatment-resistant ulcerative colitis, and the control group consisted of 24 ulcerative colitis patients responding to routine treatment. Serum vitamin D levels were measured by ELISA method. Real-time PCR was employed to quantify the relative expression of pro- and anti-inflammatory cytokines in colon biopsy samples from case and control groups. The pro-inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-8, IL-17 A, and IL-33, while the anti-inflammatory cytokines were IL-10, IL-35, and TGF-β. Data are showed as mean ± standard deviation (SD), and p values < 0.05 were considered statistically significant. The mean age of the control group was 45.88 ± 18.51 years, while that of the case group was 41.30 ± 13.01 years. The relative gene expression of TNF-α, IFN-γ, IL-1β, IL-6, IL-8, IL-17 A, IL-33, TGF-β, IL-10, and IL-35, in the case and control groups did not exhibit statistically significant differences (p > 0.05). However, the gene expression levels of the principal pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, were elevated in treatment-resistant patients compared to patients who responded to treatments. No correlation was observed between serum vitamin D levels and the gene expression of pro- and anti-inflammatory cytokines (p > 0.05). The present study did not identify a statistically significant correlation between the expression of pro- or anti-inflammatory cytokines and treatment response. Therefore, routine treatments had no effect on the expression of these cytokines in treatment-resistant patients. Additionally, serum vitamin D levels were not related to the relative expression of pro- and anti-inflammatory cytokines in the affected area of the colon of these patients. Despite the need for further research on the protective and pathological roles of cytokines and vitamin D, regular screening and early and complementary treatment may be beneficial in reducing inflammatory symptoms in these patients.

Adverse childhood experiences (ACEs) are widely recognized as associated with stress-associated digestive disorders, yet their comprehensive relationship with gastro-esophageal diseases as well as the potential mechanisms of depression remains underexplored.

The prospective study included 133,638 participants aged 40-69 from UK Biobank with full information on ACEs, depression, and gastro-esophageal diseases. ACEs were retrospectively measured both as individual types (physical, emotional, and sexual abuse, and physical and emotional neglect) and cumulative scores of experienced types. Cox proportional hazards model was utilized to assess the association of ACEs with the overall and type-specific risks of diseases. Two-sample Mendelian randomization (TSMR) was conducted utilizing data from a genome-wide association study of ACEs (N = 185,414) to further examine the causal relationship. Mediation analysis was performed to quantify the role of depression.

During a median follow-up of 13.3 years, those who had a history of ACEs were observed with a 15 % higher overall risk of gastro-esophageal diseases (HR, 1.15; 95%CI, 1.12-1.19) and 10-25 % increased type-specific risks compared to unexposed participants. Among five individual types of ACEs, the association was more prominent for emotional abuse (1.22, 1.17-1.27) and sexual abuse (1.24, 1.18-1.30). TSMR analysis consistently reported positive associations between ACE and four subtypes of gastro-esophageal diseases. Depression was found to mediate 17.2 % (13.5 %, 24.0 %) of the aforementioned relationship.

Our findings highlight the importance of early screening and intervention on ACEs to reduce the long-term risk of gastro-esophageal diseases, and stress the potential of depression as a ponderable indirect intervention target.

Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disease belonging to the inherited bone marrow failure syndromes and characterized by hypocellular bone marrow, exocrine pancreatic insufficiency, and skeletal abnormalities. SDS is associated with increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). Although SDS is not primarily considered an inflammatory disorder, some of the associated conditions (e.g., neutropenia, pancreatitis and bone marrow dysfunction) may involve inflammation or immune system dysfunctions. We have already demonstrated that signal transducer and activator of transcription (STAT)-3 and mammalian target of rapamycin (mTOR) were hyperactivated and associated with elevated IL-6 levels in SDS leukocytes. In this study, we analyzed the level of phosphoproteins involved in STAT3 and mTOR pathways in SDS lymphoblastoid cells (LCLs) and the secretomic profile of soluble pro-inflammatory mediators in SDS plasma and LCLs in order to investigate the systemic inflammation in these patients and relative pathways.

Twenty-six SDS patients and seven healthy donors of comparable age were recruited during the programmed follow-up visits for clinical evaluation at the Verona Cystic Fibrosis Center Human. The obtained samples (plasma and/or LCLs) were analyzed for: phosphoproteins, cytokines, chemokines and growth factors levels by Bio-plex technology; microRNAs profiling by next generation sequencing (NGS) and microRNAs expression validation by Real Time-PCR (RT-PCR) and droplet digital PCR (ddPCR) .

We demonstrated dysregulation of ERK1/2 and AKT phosphoproteins in SDS, as their involvement in the hyperactivation of the STAT3 and mTOR pathways confirmed the interplay of these pathways in SDS pathophysiology. However, both these signaling pathways are strongly influenced by the inflammatory environment. Here, we reported that SDS is characterized by elevated plasma levels of several soluble proinflammatory mediators. In vitro experiments show that these pro-inflammatory genes are closely correlated with STAT3/mTOR pathway activation. In addition, we found that miR-181a-3p is down-regulated in SDS. Since this miRNA acts as a regulator of several pro-inflammatory pathways such as STAT3 and ERK1/2, its down-regulation may be a driver of the constitutive inflammation observed in SDS patients.

The results obtained in this study shed light on the complex pathogenetic mechanism underlying bone marrow failure and leukemogenesis in SDS, suggesting the need for anti-inflammatory therapies for SDS patients.

Crohn's disease (CD) involves immune system interactions with intestinal tissue, driven by pro-inflammatory cytokines like Tumor Necrosis Factor (TNF-α). Adalimumab, targeting TNF-α, regulates associated inflammatory responses. Despite being humanized, it may induce immunogenic processes, affecting treatment effectiveness. Thus, monitoring serum adalimumab and anti-drug antibody (ADA) levels can optimize therapy. Understanding genetic factors influencing adalimumab response can enhance personalized treatment and improve patient quality of life. We aimed to quantify adalimumab serum levels, assess test interchangeability, detect ADA, examine immune complex formation, and investigate genetic phenotypes related to immunogenicity in CD patients. Seventy CD patients in the maintenance phase with adalimumab were classified into active (CDA) and remission (CDR) groups. Adalimumab concentration was determined via enzyme-linked immunosorbent assay (ELISA-Promonitor) and lateral flow assay (Quantum Blue), with assay interchangeability assessed statistically. ADA and immune complex formation were quantified using ELISA assays. DNA was genotyped for the genes ATG16L1, CD96, and CD155. No significant differences in adalimumab serum concentrations were observed between groups, regardless of the assay. However, a statistical difference between the tests indicated measurement disparity (P = 0.003), with moderate agreement (Lin's correlation of 0.247). ADA was detected in 4 of 27 of the patients with infratherapeutic levels, 3 in the CDA group and 1 in the CDR group. Analysis of immune complexes revealed significantly higher concentrations in the CDA group (P = 0.0125). The genotypic evaluation revealed significant associations for the CD96 CC (wild-type) genotype with higher CRP levels, colonic involvement, and infratherapeutic levels of adalimumab. ATG16L1 CC genotype was associated with higher CDEIS and fecal calprotectin values, while the variant (TT) genotype had lower platelet counts. The effectiveness of treatment with adalimumab was not directly related to higher medication levels in this cohort. The disparity between tests indicates the need to use only one test in patient follow-up to ensure accuracy in therapeutic monitoring. Genotypic differences highlight the correlation between the wild genotype for CD96 and ATG16L1 with unfavorable laboratory and endoscopic response to adalimumab. Finally, the more significant levels of immune complexes in the CDA group indicate an association with a worse response to adalimumab.

Inflammatory bowel disorders (IBD) can lead to severe complications like perforation, bleeding, and colon cancer, posing life-threatening risks. Lycium ruthenicum Murray (L. ruthenicum Murr.), rich in polysaccharides, has been utilized in traditional diets for thousands of years. This study explores the protective effects of the polysaccharide of L. ruthenicum on mice with dextran sulfate sodium (DSS)-induced colitis. In the present study, a pectic polysaccharide (LRWP-Ap) containing arabinogalactan (AG) and homogalacturonic acid (HG) structural domains with a Mw of 4.34 kDa was obtained from L. ruthenicum Murr. Fruit. The gavage administration of LRWP-Ap significantly alleviated symptoms of DSS-induced colitis in mice. In this process, LRWP-Ap modulated the balance of Arg-1/iNOS to regulate the metabolism of arginine, and the levels of intestinal tight junction (TJ) (ZO-1, Occludin, and Claudin 1) were increased by LRWP-Ap treatment, which promoted intestinal barrier function. In addition, LRWP-Ap alleviated the inflammatory response while increasing the anti-inflammatory response by reducing the level of proinflammatory factors, enhancing the level of anti-inflammatory factors (IL-10) and improving the balance of Treg/Th17 cells. These effects resulted in the maintenance of intestinal immune homeostasis. Moreover, LRWP-Ap modulated the gut microbiota composition and short-chain fatty acid (SCFA) content, which may maintain relatively favorable intestinal homeostasis. In general, LRWP-Ap has the potential to alleviate IBD, and the use of L. ruthenicum Murr. As a natural functional food to improve gut health in the context of DSS-induced colitis.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with debilitating symptoms and multifactorial etiology. Nutritional factors during adult life have been implicated in IBD pathogenesis. In addition, there is growing evidence that maternal and early-life diet may be associated with intestinal inflammation and colitis severity. The aim of the current review was to detect and critically appraise all evidence regarding the role of maternal and early-life diet on intestinal inflammation.

We performed a thorough search of the literature across two databases (Pubmed, ScienceDirect) using a variety of relevant terms.

A total of 23 studies, 16 experimental and 7 clinical, met inclusion criteria and were included in this review. Experimental studies reveal that high-fat and high-protein diets during gestation and neonatal life induce gut dysbiosis, amplify intestinal inflammation, and exacerbate colitis. In addition, a variety of nutritional factors included in maternal diets may affect offspring's microbiota composition and intestinal health. Human studies concluded that maternal diet quality and the intake of fish and vegetables and of food fortified with vitamin D during gestation and early infancy significantly decreased IBD risk. However, human data are limited, and larger investigations are needed to further clarify the complex associations between specific nutritional compounds and intestinal inflammation.

Dietary factors during pregnancy and early-life are involved in IBD pathogenesis, exerting either an exacerbating or protective effect. Improving pregnant women's dietary habits could be a cost-effective strategy to reduce future IBD burden.

Ulcerative colitis (UC) is an idiopathic, chronic, relapsing inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. The pathophysiology of UC is complicated and involves several factors including immune, genetic, and environmental factors. Recently, a huge amount of research has concentrated on the role of interleukins including interleukin-6 (IL-6) in its pathophysiology. Thus, this study aims to examine the colo-protective and immunomodulatory effect of Tocilizumab (TCZ) in an experimental model of dextran sulfate sodium (DSS) induced UC. In the current study, we analyzed the inflammatory, immunomodulatory, apoptotic, autophagy, and endoplasmic reticulum (ER) stress markers and other clinical features including stool consistency, rectal bleeding, and edema markers in rats. Our results showed that induction of colitis caused bloody diarrhea and increased IL-6 levels. Treatment with TCZ significantly ameliorated DSS-induced injury via decreasing inflammatory markers of colon injury (IL-6), signal transducer and activator of transcription-3 (STAT-3), and C-reactive protein (CRP). Furthermore, TCZ attenuated the apoptotic marker (caspase-3), and down-regulated endoplasmic reticulum stress sensor proteins (inositol- requiring transmembrane kinase endonuclease-1 (IRE-1) and activated transcription factor-6 (ATF-6)) and autophagy proteins (autophagy-related 16-like protein 1 (ATG16L1) and nucleotide-binding oligomerization domain-containing protein-2 (NOD2)), as compared to DSS group. Altogether, the current data suggest TCZ to be a promising protective therapy against UC.

This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn's disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn's Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study's findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum's potential role in modulating gut-brain interactions.

Objective Gastrointestinal (GI) disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD) can exhibit overlapping GI symptoms, including abdominal pain and alterations in bowel habits. The symptoms of GI disorders are commonly considered to be triggered and exacerbated by fatty food intake. Therefore, this study aimed to compare the food preferences of patients with GI disorders. Methods Forty food images (including fatty and light foods) and 20 animal images were selected to evaluate food preferences. The preference score was assessed using a visual analog scale ranging from 1 to 100. GI symptoms were evaluated using the GI Symptom Rating Scale (GSRS), and correlations between the GSRS and preference scores were investigated. Results Overall, 22 healthy controls and 23, 29, 27, and 20 patients with FD, IBS, GERD, and IBD, respectively, were enrolled. The preference score for all foods in patients with FD was significantly lower than that in healthy controls and those with IBS, GERD, and IBD (52.9 vs. 66.5 vs. 68.5 vs. 69.1 vs. 70.7, p<0.01). The score of fatty foods was lower in patients with FD than in healthy controls and those with IBS, GERD, and IBD (43.8 vs. 72.3 vs. 77.5 vs. 77.4 vs. 80.7, p<0.01), whereas that of light foods and animal images was not different among the groups. No significant correlation was found between the preference score and symptom severity. Conclusion Patients with FD had a negative preference for foods, particularly fatty foods, independent of the severity of GI symptoms.

The prime function of the epithelium is to regulate the intestinal permeability; the latter is a quantitative parameter that refers to the measurement of the rate of passage of solutes through the epithelial monolayer. Function of epithelial monolayer depends on the expression of protein complexes known as tight junction proteins; whose function and expression can be disrupted under conditions of inflammation including irritable bowel disease (IBD), intestinal infections, and high-fat diets, among others. This manuscript is focused to outline the effects of bovine milk protein derivatives on the intestinal permeability addressed mostly in animal models in which the intestinal barrier is disrupted. At present, the properties of bovine milk protein derivatives on intestinal permeability have been scarcely documented in humans, but evidence raised from clinical trials provides promising findings of potential application of colostrum to control of the intestinal permeability in critically ill patients, users of non-steroid anti-inflammatory drugs, like athletes and militia members.

Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes and an unclear etiology. Given the limitations of current therapeutic options, which include suboptimal efficacy and significant side effects, there is a pressing need to explore novel treatments. Probiotics derived from diverse species have been identified as a promising approach for managing IBD, owing to their anti-inflammatory properties and their ability to regulate gut flora, among other beneficial effects.

In this study, three strains of lactic acid bacteria (LAB) were isolated from the feces of the scavenger spotted hyena (Crocuta crocuta), a scavenging mammal. Based on their capability to survive within and adhere to the gastrointestinal tract, along with their profile of antibiotic resistance, a high-quality strain of Lactobacillus acidophilus (LA) was selected and demonstrated to be safe for mice. Subsequently, the therapeutic efficacy of LA was evaluated using a dextran sulfate sodium (DSS)-induced model of ulcerative colitis in mice.

The results indicated that LA restored the disease activity index and improved histopathological lesions in the model group. It also reduced inflammation and oxidative stress and significantly restored the expression of mucins and intestinal tight junction (TJ) proteins (ZO-1, Occludin). Furthermore, LA corrected the DSS-induced disruption of the intestinal flora, leading to a significant decrease in the prevalence of potentially harmful bacterial genera, such as Bacteroides, and an increase in beneficial bacterial genera, including Lactobacillus. In conclusion, Lactobacillus acidophilus LA1, isolated from spotted hyena feces, has potential as a functional supplement for alleviating symptoms of IBD and regulating intestinal flora.

This study aims to assess whether the association between chronic pathologies and depressive and/or anxious disorders is high, resulting in a reduction in the patient's quality of life.

This is a prospective cross-sectional study with a descriptive and analytical design. Sociodemographic data and lifestyle habits were collected. Subsequently, the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Hospital Anxiety and Depression Scale (HADS) were applied.

A total of 141 patients participated in the study, with a mean age of 45.78 (SD 16.01) years, of which 60.3% were female (n=85) and 39.7% were male (n=56). 58.9% had ulcerative colitis (UC) (n=83), and 41.1% had Crohn's disease (CD) (n=58). 16.5% of patients had a previous diagnosis of generalized anxiety disorder (GAD) and/or major depression (MD) (n=23). Regarding IBDQ scores, participants with anxiety had significantly lower mean scores in all IBDQ items (p<0.001), while the depression diagnosis obtained significantly lower mean values for systemic (p=0.015), emotional (p=0.001), and intestinal symptoms (p=0.005).

The results indicate that anxiety and depression negatively impact the quality of life of patients with IBD independently of the disease activity.

The NOD2 signaling pathway, which plays an important role in the mechanisms of inflammatory bowel disease (IBD) development, has been closely associated with ubiquitination. It was revealed in this study that NOD2 receptor activation could obviously affect the expression of 19 ubiquitination-related genes, with N4BP3 being the most prominently expressed and upregulated. In addition, N4BP3 knockdown was found to reduce the mRNA levels of MDP-induced inflammatory factors, while N4BP3 overexpression elevated their mRNA levels as well as the levels of phospho-ERK1/2, phospho-JNK, phospho-P38 and phospho-NF-κB P65 proteins. Immunoprecipitation tests showed that N4BP3 could pull down RIPK2 and promote its K63-linked ubiquitination. In human tissue specimen assays and mouse experiments, we found that the expression of N4BP3 was significantly elevated in Crohn's disease (CD) patients and IBD mice, and N4BP3 knockdown reduced the dextran sulfate sodium-induced pathological score and the expression of inflammatory factors in the mouse colon tissue. In conclusion, N4BP3 is able to interact with RIPK2 and promote its K63-linked ubiquitination, to further promote the NOD2-MAPK/NF-κB pathway, thereby increasing promoting the release of inflammation factors and the degree of IBD inflammation.

Microbiome research has predominantly focused on the oral cavity and oropharynx's role in disease, while the upper airway, specifically the larynx and trachea, has been relatively overlooked. Examining the microbial communities in these regions can shed light on how dysbiosis influences diseases and their management. This review evaluates laryngotracheal microbial compositions in both healthy and diseased patients.

We conducted a systematic review in EMBASE, MEDLINE, and Cochrane Central databases, yielding 1383 studies in the initial search. Inclusion criteria involved participants aged over 18 years and the use of next-generation 16s ribosomal sequencing methods.

We included 10 studies-seven focused on larynx sequencing and four on trachea sequencing (one investigated both sites). In a healthy larynx, diverse species such as Streptococcus, Cloacibacterium, Prevotella, and Helicobacter were found. Benign laryngeal diseases exhibited reduced microbial diversity, mainly dominated by Streptococcus. Subglottic stenosis patients showed diminished diversity in both idiopathic and iatrogenic scars. Laryngeal squamous cell carcinoma displayed increased diversity, primarily featuring Fusobacterium. Among non-respiratory-compromised surgery patients, the tracheal microbiome was more diverse in diabetics and those later developing lower respiratory infections. Pneumonia patients exhibited an abundance of Prevotella and Streptococcus, linked to an increased 28-day survival rate, while Streptococcus and Haemophilus abundance correlated with successful extubation.

The laryngotracheal region hosts a unique microbial community influenced by both benign and malignant conditions. Many lesions remain unexplored, underscoring the need for future studies encompassing diverse laryngotracheal conditions. Clinical trials assessing microbiome modifications may unveil novel therapeutic avenues.

NA Laryngoscope, 134:4167-4175, 2024.

Recent reports have suggested a link between rosacea and several gastrointestinal diseases, although the evidence has largely been limited to European and Asian populations. This study seeks to confirm and expand upon the connection between rosacea and gastrointestinal conditions using the diverse All of Us database.

We identified 8,319 rosacea patients and selected 4:1 controls matched (n = 33,276) based on age, race, gender, smoking status, insurance status, annual income, education, and alcohol use. Conditional logistic regression was then performed on the matched cohort to assess the relationship between rosacea and Crohn's disease (CD), microscopic colitis, ulcerative colitis (UC), celiac disease (CED), irritable bowel syndrome (IBS), Helicobacter-associated disease, and gastroesophageal reflux disease (GERD).

On logistic regression, rosacea patients were significantly more likely than matched controls to be diagnosed with IBS (odds ratio [OR]: 2.35, 95% confidence interval [CI]: 2.18-2.53, p < 0.001), CD (OR: 1.82, 95% CI: 1.53-2.15, p < 0.001), UC (OR: 1.70, 95% CI: 1.44-2.02, p < 0.001), CED (OR: 1.93, 95% CI: 1.59-2.34, p < 0.001), Helicobacter-associated disease (OR: 1.79, 95% CI: 1.50-2.14, p < 0.001), and GERD (OR: 2.07, 95% CI: 1.97-2.18, p < 0.001). However, there was no statistically significant association between rosacea and microscopic colitis (OR: 1.47, 95% CI: 0.91-2.37, p = 0.12).

This study highlights the presence of notable gastrointestinal comorbidities among individuals with rosacea in a diverse cohort. Consequently, more targeted monitoring of gastrointestinal diseases in rosacea patients may be warranted, as well as potential further investigation into the gut-skin axis in terms of rosacea pathophysiology.

Inflammatory bowel disease (IBD) is characterized by persistent inflammation and is often associated with metabolic dysfunction-associated steatotic liver disease (MASLD). IBD patients are at risk of developing MASLD due to shared risk factors such as gut dysbiosis and systemic inflammation. The new MASLD nomenclature emphasizes the link between liver steatosis and cardiometabolic comorbidities. However, the prevalence of MASLD in IBD patients remains poorly explored. The main aim of this cross-sectional study is to assess the prevalence of ultrasound (US) and the clinical features of MASLD in patients with IBDs.

We conducted a retrospective study enrolling 272 Italian IBD patients attending Renato Dulbecco Teaching Hospital in a period between 1 January 2021 and 31 December 2023. MASLD was diagnosed based on the presence of liver steatosis with cardiometabolic risk factors, using established guidelines. Demographic, clinical, and laboratory data were collected and analyzed. Statistical significance was determined at a p-value < 0.05.

Of the 272 IBD patients, 6% had non-alcoholic fatty liver disease (NAFLD), while 18% had MASLD. Patients with IBD-MASLD were significantly older, had higher body mass index, waist circumference, and triglyceride levels, and were more likely to have type 2 diabetes mellitus and hypertension compared to those with IBD-NAFLD. IBD-MASLD patients also showed higher disease activity scores and required more frequent surgical interventions. Bivariate logistic regression revealed triglyceride levels as a significant predictor of MASLD in IBD patients.

MASLD is more prevalent in IBD patients, highlighting the importance of early detection of liver steatosis in this at-risk population. The association between MASLD and cardiometabolic risk factors underscores the need for a multidisciplinary approach to manage these patients effectively. Further studies in larger cohorts are necessary to confirm these findings and explore the pathophysiological mechanisms involved.

The two primary forms of inflammatory disorders of the small intestine andcolon that make up inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). While ulcerative colitis primarily affects the colon and the rectum, CD affects the small and large intestines, as well as the esophagus,mouth, anus, andstomach. Although the etiology of IBD is not completely clear, and there are many unknowns about it, the development, progression, and recurrence of IBD are significantly influenced by the activity of immune system cells, particularly lymphocytes, given that the disease is primarily caused by the immune system stimulation and activation against gastrointestinal (GI) tract components due to the inflammation caused by environmental factors such as viral or bacterial infections, etc. in genetically predisposed individuals. Maintaining homeostasis and the integrity of the mucosal barrier are critical in stopping the development of IBD. Specific immune system cells and the quantity of secretory mucus and microbiome are vital in maintaining this stability. Th22 cells are helper T lymphocyte subtypes that are particularly important for maintaining the integrity and equilibrium of the mucosal barrier. This review discusses the most recent research on these cells' biology, function, and evolution and their involvement in IBD.

Cannabis sativa L. has a long history of medicinal use, particularly for gastrointestinal diseases. Patients with inflammatory bowel disease (IBD) report using cannabis to manage their symptoms, despite little data to support the use of cannabis or cannabis products to treat the disease. In this study, we use the well-described dextran sodium sulfate (DSS) model of colitis in mice to assess the impact of commercially available, noneuphorigenic, high cannabigerol (CBG) hemp extract (20 mg/mL cannabigerol, 20.7 mg/mL cannabidiol, 1 mg/mL cannabichromene) on IBD activity and the colonic microbiome. Mice were given 2% DSS in drinking water for 5 days, followed by 2 days of regular drinking water. Over the 7 days, mice were dosed daily with either high CBG hemp extract or matched vehicle control. Daily treatment with high CBG hemp extract dramatically reduces the severity of disease at the histological and organismal levels as measured by decreased disease activity index, increased colon length, and decreases in percent colon tissue damage. 16S rRNA gene sequencing of the fecal microbiota reveals high CBG hemp extract treatment results in alterations in the microbiota that may be beneficial for colitis. Finally, using metabolomic analysis of fecal pellets, we find that mice treated with high CBG hemp extract have a normalization of several metabolic pathways, including those involved in inflammation. Taken together, these data suggest that high CBG hemp extracts may offer a novel treatment option for patients. SIGNIFICANCE STATEMENT: Using the dextran sodium sulfate model of colitis, the authors show that treatment with high cannabigerol hemp extract reduces the severity of symptoms associated with colitis. Additionally, they show that treatment modulates both the fecal microbiota and metabolome with potential functional significance.

Quality of life (QoL) in patients with inflammatory bowel disease (IBD) is influenced by several factors, many of which may also impact cognitive function. However, the extent of the interaction among these factors, QoL, and disease outcomes in IBD patients remains unknown. We thus aim to characterize the relationships among psychological disorders, coping mechanisms, cognitive function, and the overall impact on QoL and disease outcomes in patients with IBD. This cross-sectional observational study was conducted at an academic care center. QoL was evaluated using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and disease severity was evaluated using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and the Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). We also used the Hospital Anxiety and Depression scale (HADS). Regression models were used to test the associations among QoL, number of hospitalizations, disease severity, cognitive functioning (working memory [WM] and reaction time), and coping strategies while controlling for anxiety and depressive symptoms, age, and sex. This study included 41 patients (24 patients with CD and 17 with UC) whose mean age was 28.2 (±8.4) years (23 males) and mean SIBDQ score was 51.5 (±10.0). Patients with more WM errors had lower QoL scores (P = .041), whereas patients with higher anxiety levels had lower QoL and more active UC (P = .008 and P = .016, respectively). The use of avoidant coping mechanisms was associated with a significantly higher number of hospitalizations (P = .038), and patients who adopted more emotion-focused coping strategies had a longer illness duration (P = .021). Finally, patients with higher education levels were found to use more active coping mechanisms than others. These results confirm the impact of cognitive, psychological, and coping factors on QoL and disease outcomes in patients with IBD; however, the mechanisms by which these factors interrelate remain unclear. Therapies aimed at improving both cognitive functions and psychological conditions may thus be effective at improving QoL and disease outcomes in IBD patients, and education may play a positive role in promoting the adoption of more effective coping strategies among IBD patients.

The term "inflammatory bowel disease" (IBD) describes a class of relapse-remitting conditions that affect the gastrointestinal (GI) tract. Among these, Crohn's disease (CD) and ulcerative colitis (UC) are two of the most globally prevalent and debilitating conditions. Several articles have brought attention to the significant role that inflammation and oxidative stress cooperatively play in the development of IBD, offering a different viewpoint both on its etiopathogenesis and on strategies for the effective treatment of these conditions. Marine ecosystems may be a significant source of physiologically active substances, supporting the search for new potential clinical therapeutics. Based on this evidence, this review aims to comprehensively evaluate the activity of marine algae and deriving biomolecules in decreasing pathological features of CD and UC. To match this purpose, a deep search of the literature on PubMed (MEDLINE) and Google Scholar was performed to highlight primary biological mechanisms, the modulation of inflammatory and oxidative stress biochemical parameters, and potential clinical benefits deriving from marine species. From our findings, both macroalgae and microalgae have shown potential as therapeutic solutions for IBD due to their bioactive compounds and their anti-inflammatory and antioxidant activities which are capable of modulating markers such as cytokines, the NF-κB pathway, reactive oxidative and nitrosative species (ROS and RNS), trefoil factor 3 (TFF3), lactoferrin, SIRT1, etc. However, while we found promising preclinical evidence, more extensive and long-term clinical studies are necessary to establish the efficacy and safety of marine algae for IBD treatment.

Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the gastrointestinal tract (GI), characterized by recurrent episodes of inflammation and tissue destruction. It affects an increasing number of individuals worldwide who suffer from Crohn's disease (CD) or ulcerative colitis (UC). Despite substantial advances in understanding the underlying causes of IBD, the available treatments remain restricted and are sometimes accompanied by severe consequences. Consequently, there is an urgent need to study alternate therapeutic options. This review assesses the present drugs, identifies their limitations, and proposes the use of saffron, a natural plant with great therapeutic potential based on preclinical and clinical investigations. Saffron has gained attention for its potential therapeutic benefits in treating various ailments due to its established bioactive compounds possessing antioxidant and anti-inflammatory properties. This review covers how saffron impacts the levels of calprotectin, an inflammatory marker, for various inflammatory responses in multiple diseases including IBD. Data from clinical trials were assessed to determine the efficacy and safety of using saffron to counter inflammation in multiple diseases. Studies have shown that saffron may protect against inflammatory bowel disease (IBD) through several mechanisms by inhibiting pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), reducing oxidative stress through antioxidant effects, enhancing mucosal barrier function by upregulating tight junction proteins, and modulating the gut microbiota composition to promote beneficial bacteria while suppressing pathogenic ones; these combined actions contribute to its therapeutic potential in managing and alleviating the symptoms of IBD. This will enable future research endeavors and expedite the translation of saffron-based interventions into clinical practice as a valuable adjunctive therapy or a potential alternative to conventional treatments, thereby enhancing the quality of life for individuals suffering from inflammatory diseases including IBD.

The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.

The imbalance of gut microbiota is an important factor leading to inflammatory bowel disease (IBD). Diffusible signal factor (DSF) is a novel quorum-sensing signal that regulates bacterial growth, metabolism, pathogenicity, and host immune response. This study aimed to explore the therapeutic effect and underlying mechanisms of DSF in a zebrafish colitis model induced by sodium dextran sulfate (DSS). The results showed that intake of DSF can significantly improve intestinal symptoms in the zebrafish colitis model, including ameliorating the shortening of the intestine, reducing the increase in the goblet cell number, and restoring intestinal pathological damage. DSF inhibited the upregulation of inflammation-related genes and promoted the expression of claudin1 and occludin1 to protect the tightness of intestinal tissue. The gut microbiome analysis demonstrated that DSF treatment helped the gut microbiota of the zebrafish colitis model recover to normal at the phylum and genus levels, especially in terms of pathogenic bacteria; DSF treatment downregulated the relative abundance of Aeromonas hydrophila and Staphylococcus aureus, and it was confirmed in microbiological experiments that DSF could effectively inhibit the colonization and infection of these two pathogens in the intestine. This study suggests that DSF can alleviate colitis by inhibiting the proliferation of intestinal pathogens and inflammatory responses in the intestine. Therefore, DSF has the potential to become a dietary supplement that assists in the antibiotic and nutritional treatment of IBD.

Previous observational studies revealed the potential correlation between psychiatric disorders (PDs) and non-tumor gastrointestinal diseases (NTGDs). However, their causation remains unclear.

We explored the causal relationship between PDs and NTGDs through bidirectional two-sample Mendelian randomization (MR) study. Large-scale genome-wide association study (GWAS) summary statistics and bidirectional two-sample MR study were used to assess the causality between PDs and NTGDs. Multiple sensitivity analyses were used to identify the robustness of our results.

We found that major depression was causally associated with increased risk of gastric ulcer (OR: 1.812, 95% CI: 1.320-2.487, p < 0.001) and irritable bowel syndrome (OR: 1.645, 95% CI: 1.291-2.097, p < 0.001). Meanwhile, genetically predicted gastroesophageal reflux disease contributed to the increased risk of anxiety disorders (OR: 1.425, 95% CI: 1.295-1.568, p < 0.001), and ulcerative colitis was related to increased risk of attention deficit/hyperactivity disorder (OR: 1.042, 95% CI: 1.008-1.078, p = 0.0157).

Our study provided MR evidence to support the close causality and identify the specific direction between eight PDs and eight common NTGDs. Experimental studies to further examine the causality, underlying mechanism, and therapeutic potential of PDs and NTGDs are required.

Fucoidan is widely applied in food and pharmaceutical industry for the promising bioactivities. Low-molecular weight hydrolyzed fucoidan has gained attention for its beneficial health effects. Here, the modulation on microbiome and metabolome features of fucoidan and its acidolyzed derivatives (HMAF, 1.5-20 kDa; LMAF, <1.5 kDa) were investigated through human fecal cultures. Fucose is the main monosaccharide component in fucoidan and LMAF, while HMAF contains abundant glucuronic acid. LMAF fermentation resulted in the highest production of short-chain fatty acids, with acetate and propionate reaching maximum levels of 13.46 mmol/L and 11.57 mmol/L, respectively. Conversely, HMAF exhibited a maximum butyrate production of 9.28 mmol/L. Both fucoidan and acidolyzed derivatives decreased the abundance of Escherichia-Shigella and Klebsiella in human fecal cultures. Fucoidan and HMAF prefer to improve the abundance of Bacteroides. However, LMAF showed positive influence on Bifidobacterium, Lactobacillus, and Megamonas. Untargeted metabolome indicated that fucoidan and its derivatives mainly altered the metabolic level of lipids, indole, and their derivatives, with fucoidan and HMAF promoting higher level of indole-3-propionic acid and indole-3-carboxaldehyde compared to LMAF. Considering the chemical structural differences, this study suggested that hydrolyzed fucoidan can provide potential therapeutic applications for targeted regulation of microbial communities.

Psychological characterization of patients affected by Inflammatory Bowel Disease (IBD) focuses on comorbidity with psychiatric disorders, somatization or alexithymia. Whereas IBD patients had higher risk of stable anxiety and depression for many years after the diagnosis of the disease, there is a lack of studies reporting a comprehensive psychosomatic assessment addressing factors of disease vulnerability, also in the long-term. The objective of this investigation is to fill this gap in the current literature. The aims were thus to assess: a) changes between baseline and a 4-year follow-up in psychiatric diagnoses (SCID), psychosomatic syndromes (DCPR), psychological well-being (PWB-I), lifestyle, gastrointestinal symptoms related to IBD and Irritable Bowel Syndrome (IBS)-like symptoms b) stability of psychiatric and psychosomatic syndromes at 4-year follow-up. A total of 111 IBD outpatients were enrolled; 59.5% of them participated at the follow-up. A comprehensive assessment, including both interviews and self-report questionnaires, was provided at baseline and follow-up. Results showed increased psychiatric diagnoses, physical activity, consumption of vegetables and IBS-like symptoms at follow-up. Additionally, whereas psychiatric diagnoses were no longer present and new psychopathological pictures ensued at follow-up, more than half of the sample maintained psychosomatic syndromes (particularly allostatic overload, type A behavior, demoralization) from baseline to follow-up. Long-term presence/persistence of such psychosocial burden indicates the need for integrating a comprehensive psychosomatic evaluation beyond traditional psychiatric nosography in IBD patients. Moreover, since psychosomatic syndromes represent vulnerability factors of diseases, further studies should target subgroups of patients presenting with persistent psychosomatic syndromes and worse course of the disease.

Corticotropin-releasing factor family peptides (CRF peptides) comprise corticotropin releasing hormone (CRH), urocortin (UCN1), UCN2 and UCN3. CRH is first isolated in the brain and later with UCNs found in many peripheral cells/tissues including the colon. CRH and UCNs function via the two types of receptors, CRF1 and CRF2, with CRH mainly acting on CRF1, UCN1 on both CRF1 &CRF2 and UCN2-3 on CRF2. Compiling evidence shows that CRH participates in inflammation and cancers via both indirect central effects related to stress response and direct peripheral influence. CRH, as a stress-response mediator, plays a significant central role in promoting the development of colitis involving colon motility, immunity and gut flora, while a few anti-colitis results of central CRH are also reported. Moreover, CRH is found to directly influence the motility and immune/inflammatory cells in the colon. Likewise, CRH is believed to be greatly related to tumorigenesis of many kinds of cancers including colon cancer via the central action during chronic stress while the peripheral effects on colitis-associated-colon cancer (CAC) are also proved. We and others observe that CRH/CRF1 plays a significant peripheral role in the development of colitis and CAC in that CRF1 deficiency dramatically suppresses the colon inflammation and CAC. However, up to date, there still exist not many relevant experimental data on this topic, and there seems to be no absolute clearcut between the central and direct peripheral effects of CRH in colitis and colon cancer. Taken together, CRH, as a critical factor in stress and immunity, may participate in colitis and CAC as a centrally active molecule; meanwhile, CRH has direct peripheral effects regulating the development of colitis and CAC, both of which will be summarized in this review.

Abaecin is a natural antimicrobial peptide (AMP) rich in proline from bees. It is an important part of the innate humoral immunity of bees and has broad-spectrum antibacterial ability. This study aimed to determine the effect of Abaecin on dextran sulfate sodium (DSS) -induced ulcerative colitis (UC) in mice and to explore its related mechanisms. Twenty-four mice with similar body weight were randomly divided into 4 groups. 2.5% DSS was added to drinking water to induce colitis in mice. Abaecin and PBS were administered rectally on the third, fifth, and seventh days of the experimental period. The results showed that Abaecin significantly alleviated histological damage and intestinal mucosal barrier damage caused by colitis in mice, reduced the concentration of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ, and the phosphorylation of NF-κB / MAPK inflammatory signaling pathway proteins, and improved the composition of intestinal microorganisms. These findings suggest that Abaecin may have potential prospects for the treatment of UC.

Background: Inflammatory bowel diseases (IBDs) have seen an exponential increase in incidence, particularly among pediatric patients. Psychological stress is a significant risk factor influencing the disease course. This review assesses the interaction between stress and disease progression, focusing on articles that quantified inflammatory markers in IBD patients exposed to varying degrees of psychological stress. Methods: A systematic narrative literature review was conducted, focusing on the interaction between IBD and stress among adult and pediatric patients, as well as animal subjects. The research involved searching PubMed, Scopus, Medline, and Cochrane Library databases from 2000 to December 2023. Results: The interplay between the intestinal immunity response, the nervous system, and psychological disorders, known as the gut-brain axis, plays a major role in IBD pathophysiology. Various types of stressors alter gut mucosal integrity through different pathways, increasing gut mucosa permeability and promoting bacterial translocation. A denser microbial load in the gut wall emphasizes cytokine production, worsening the disease course. The risk of developing depression and anxiety is higher in IBD patients compared with the general population, and stress is a significant trigger for inducing acute flares of the disease. Conclusions: Further large studies should be conducted to assess the relationship between stressors, psychological disorders, and their impact on the course of IBD. Clinicians involved in the medical care of IBD patients should aim to implement stress reduction practices in addition to pharmacological therapies.

This review reveals details of the interaction between disorders of gut-brain interaction (DGBI) and inflammatory bowel disease (IBD) by providing an in-depth review of that relationship. The review provides a nuanced understanding of this multifaceted dynamic by spanning shared symptomatology, the impact of inflammation on functional aspects, and addressing diagnostic challenges, psychological influences, treatment strategies, and emerging research directions. By synthesizing current knowledge and identifying gaps in understanding, this article aims to contribute to the evolving discourse surrounding the interplay between IBD and DGBI, offering valuable insights for clinicians, researchers, and healthcare professionals navigating the complexities of gastrointestinal health.

The main cause of inflammatory bowel disease (IBD) is abnormal intestinal permeability due to the disruption of the tight junction of the intestinal barrier through a pathogen-mediated inflammatory mechanism and an imbalance of the gut microbiota. This study aimed to evaluate whether 2-ketoglutaric acid alleviated permeability dysfunction with tight junction localization, activated the transforming growth factor beta-activated kinase 1 (TAK1) inflammation pathway, and regulated the homeostasis of the intestinal microbiome in vitro and in vivo IBD model. Our findings revealed that 2-ketoglutaric acid significantly suppressed abnormal intestinal permeability, delocalization of tight junction proteins from the intestinal cell, expression of inflammatory cytokines, such as TNF-α, both in vitro and in vivo. 2-Ketoglutaric acid was found to directly bind to TAK1 and inhibit the TNF receptor-associated factor 6 (TRAF6)-TAK1 interaction, which is related to the activation of nuclear factor kappa B (NF-κB) pathways, thereby regulating the expression of mitogen-activated protein kinase. Dietary 2-ketoglutaric acid also alleviated gut microbiota dysbiosis and IBD symptoms, as demonstrated by improvements in the intestine length and the abundance of Ligilactobacillus, Coriobacteriaceae_UCG_002, and Ruminococcaceae_unclassified in mice with colitis. This study indicated that 2-ketoglutaric acid binds to TAK1 for activity inhibition which is related to the NF-κB pathway and alleviates abnormal permeability by regulating tight junction localization and gut microbiome homeostasis. Therefore, 2-ketoglutaric acid is an effective nutraceutical agent and prebiotic for the treatment of IBD.

Both ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases with unknown etiologies and are rare. However, the odds ratio in UC patients has been reported to range from 1.7 to 2.1, suggesting a potential etiology between sarcoidosis and UC. Furthermore, the underlying etiologies of UC and sarcoidosis remain unidentified. Sharing the experience of a UC patient with cardiac sarcoidosis could provide valuable insights to prevent sudden death in UC patients.

A 71-year-old Japanese woman was diagnosed with UC at 58-year-old and maintained remission on mesalazine treatment. She complained of just palpitation; therefore, she consulted a cardiologist.

The patient received a diagnosis of cardiac sarcoidosis with complicating ulcerative colitis based on the results of N-terminal prohormone of the brain natriuretic peptide (NT-proBNP), imaging examinations, and histology.

The patient was treated with prednisolone and methotrexate. The prednisolone was then tapered, and the methotrexate dose was adjusted based on her symptoms, imaging results, and laboratory findings.

She no longer had any symptoms, and the abnormal FDG uptake had disappeared after 2 years.

In UC patients, periodic or additional (in case of symptomatic) electrocardiography and NT-proBNP are recommended for the early detection of cardiac sarcoidosis, a life-threatening complication.