OBJECTIVES: The risk factors and role of mother‒child gut microbiota in pediatric inflammatory bowel disease (PIBD) remain unclear. We aimed to explore the clinical risk factors associated with PIBD, analyze the characteristics of gut microbiota of children and their mothers, and examine the correlation of the microbial composition in mother‒child pairs. METHODS: We conducted a case-control study including children with PIBD and their mothers as the case group, as well as healthy children and their mothers as the control group. Questionnaires were used to collect information such as family illness history and maternal and early-life events. Fecal samples were collected from the children and mothers for microbiota 16S ribosomal RNA (rRNA) sequencing to analyze the composition and its potential association with PIBD. RESULTS: A total of 54 pairs of cases and 122 pairs of controls were recruited. A family history of autoimmune disease and antibiotic use during pregnancy were associated with an increased risk of PIBD, and a higher education level of the father was associated with a decreased risk of PIBD. Children with PIBD and mothers exhibited different gut microbiota compared to healthy children and mothers. Similarities were observed in the gut microbiota of mothers and children in the same groups. Some bacterial biomarkers of mothers discovered in this study had the power to predict PIBD in their offspring. CONCLUSIONS PIBD is influenced by maternal risk factors and has unique gut microbiota characteristics. The mother‒child gut microbiota is closely related, suggesting the transmission and influence of the gut microbiota between mothers and children. This study highlights the potential pathogenesis of PIBD and provides a basis for developing targeted interventions.
Humans ; Gastrointestinal Microbiome ; Female ; Risk Factors ; Case-Control Studies ; Male ; Child ; Inflammatory Bowel Diseases/etiology* ; Adult ; RNA, Ribosomal, 16S/genetics* ; Feces/microbiology* ; Mothers ; Pregnancy ; Child, Preschool

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

In recent years, Janus kinase (JAK) inhibitors have been gradually approved for the treatment of immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis, giant cell arteritis, atopic dermatitis, alopecia areata, psoriasis, and inflammatory bowel disease. To standardize the application of JAK inhibitors in IMIDs, the expert group of this consensus has formulated the Chinese expert consensus on the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors, based on the latest research data, relevant guidelines, domestic and international literature, and clinical practice experience of the experts. This consensus provides a comprehensive introduction to treatment regimens, safety management, and medication use in specific populations, aiming to assist clinicians in making reasonable clinical decisions.
Humans ; Janus Kinase Inhibitors/therapeutic use* ; Consensus ; Inflammation/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; East Asian People

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Objective To investigate the impact of the triglyceride-glucose(TyG)index on the risk of inflammatory bowel disease(IBD).Methods Based on the data from UK Biobank,participants were allocated into three groups,TyG1(≤4.564),TyG2(4.564-4.808),and TyG3(≥4.808),according to tertiles of the TyG index.Kaplan-Meier curves were established to analyze the cumulative incidence of IBD.Further,Cox proportional hazard regression was employed to analyze the hazard ratio(HR)and its 95% confidential interval(95%CI)of each group.The same analysis was conducted for different subtypes(ulcerative colitis and Crohn's disease)of IBD.Sensitive analysis based on the competing risk model was performed after excluding participants who were diagnosed within one year.Results A total of 116 423 participants were included in this study,with the median follow-up time of 12.56 years.The incidence densities of IBD in the TyG1,TyG2,and TyG3 groups were 4.47,5.94,and 6.50 per 10 000 person-year,respectively.The cumulative incidence of IBD increased with the rise in TyG,and Log-rank test results showed differences in cumulative incidence between groups(P<0.001).After adjusting the confounding factors,the HR(95%CI)of IBD in the TyG2 and TyG3 groups was 1.50(1.21-1.85)and 1.71(1.36-2.16),respectively.The results of the subgroup analysis after adjusting the confounding factors revealed that the HR(95%CI)of ulcerative colitis and Crohn's disease in the TyG3 group was 1.48(1.16-1.74)and 2.27(1.51-3.42),respectively.The sensitive analysis yielded similar results after excluding participants who were diagnosed within one year.Conclusion A high TyG index indicates an increased risk of IBD and its subtypes.
Humans ; Inflammatory Bowel Diseases/blood* ; Triglycerides/blood* ; Incidence ; Blood Glucose/analysis* ; Male ; Female ; Risk Factors ; Proportional Hazards Models ; Adult ; Middle Aged ; Crohn Disease/epidemiology*

Objective To compare the diagnostic value of transabdominal intestinal ultrasound (IUS) and magnetic resonance enterography (MRE) for intestinal stenosis in inflammatory bowel disease (IBD). Methods A retrospective analysis was conducted on the imaging features of 51 IBD patients who underwent both IUS and MRE at Beijing Friendship Hospital,Capital Medical University,between January 2021 and February 2025.With endoscopy as the gold standard,the diagnostic performance of the two methods was compared. Results The sensitivity (84.2% vs. 52.6%,P=0.008) and accuracy (66.7% vs. 45.1%,P=0.035) of IUS for stenosis were higher than those of MRE.In the localization of stenosis,IUS demonstrated higher sensitivity than MRE for detecting stenosis in the terminal ileum (78.6% vs. 35.7%,P=0.070) and colorectum (86.7% vs. 53.3%,P=0.060).Furthermore,IUS showed higher diagnostic accuracy than MRE for terminal ileum stenosis (70.6% vs. 29.4%,P=0.039).The intestinal wall thickness[(8.2±2.7) mm vs. (10.3±3.8) mm;t=3.20,P=0.002)] and stenosis inner diameter[(3.0±1.6) mm vs. (4.3±1.8) mm;t=2.15,P=0.035] measured by IUS were lower than those measured by MRE,with a moderate level of consistency (ICC:0.19-0.53).In addition,IUS demonstrated a higher detection rate for mesenteric fat hypertrophy (70.6% vs. 27.5%,Kappa=0.27,P=0.005),whereas MRE was more sensitive in detecting lymphadenopathy (90.2% vs. 56.9%,Kappa=0.16,P=0.080). Conclusions IUS is superior to MRE in the diagnosis and localization sensitivity for intestinal stenosis in IBD.However,the two methods showcase poor consistency in detecting and quantitating some inflammatory signs.IUS can be used as a first-line screening method for diagnosing intestinal stenosis in IBD patients,while its clinical application should be combined with specific needs to optimize diagnosis.
Humans ; Retrospective Studies ; Constriction, Pathologic/diagnostic imaging* ; Ultrasonography/methods* ; Magnetic Resonance Imaging/methods* ; Inflammatory Bowel Diseases/diagnostic imaging* ; Male ; Female ; Adult ; Middle Aged ; Intestines/diagnostic imaging* ; Sensitivity and Specificity

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.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.
Humans ; Inflammatory Bowel Diseases/therapy*

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans ; Fibrosis/metabolism* ; Inflammatory Bowel Diseases/pathology* ; Animals ; Transforming Growth Factor beta/metabolism* ; Intestines/pathology*