Electroacupuncture at Zusanli regulates the pathological phenotype of inflammatory bowel disease by modulating the NLRP3 inflammasome pathway.

BACKGROUND: This study sought to explore the effect of electroacupuncture (EA) intervention at Zusanli (ST36) acupoint on modulating the NLRP3 inflammasome pathway for treating inflammatory bowel disease (IBD). METHODS: C57BL/6 mice were administrated with 3% dextran sulfate sodium (DSS) to construct the IBD model. DSS mice were then administrated with EA (10 Hz, 1.5 mA) at ST36 for 7 days or intragastric administration of sulfasalazine (SASP) each day during the entire course. The control group animals were administered with distilled water. Then, partial least squares discriminant analysis revealed differences in the relative content of metabolites. The pathological changes of colon and spleen tissues were observed by H&E and immunohistochemistry (IHC) staining. qPCR determined the mRNA expression levels, while ELISA and western blot analysis determined the protein expression. RESULTS: Compared with the control groups, DSS-induced decreases of body weight were reversed after EA stimulation at ST36 or SASP treatment. The DAI of DSS mice was significantly higher relative to the control groups, whereas the DAI of DSS mice were decreased after EA stimulation at ST36 or SASP treatment. The intestinal weight/length ratio increased significantly in DSS groups; however, EA at ST36 significantly improved the macroscopic/microscopic characteristics and the weight and length of the colon. EA reversed inflammation and leukocyte infiltration and normalized the elevated levels of IL-1ß, IL-18, and NLRP3. Furthermore, EA improved the expression levels of ZO-1, occludin, and claudin 1, exhibiting normalization of the colon's tight junctions. CONCLUSIONS: EA at Zusanli acupoint of colon tissue significantly improved the pathological phenotype, showing a therapeutic effect on IBD.

Utilizing a multisystemic model of resilience to synthesize research in youth with inflammatory bowel disease: a narrative review.

Background and Objective: The study of resilience in youth with inflammatory bowel disease (IBD) is in early stages. The current review aims to illustrate how the use of a multisystemic framework may serve as a developmental and disease-appropriate framework for conceptualizing and designing resilience research for youth with IBD. Methods: This is a narrative review; therefore, a comprehensive and systematic literature search was not conducted. Rather, the current paper aims to map selected existing literature to a multisystemic model as exemplars of how the model may be used in youth with IBD. Relevant literature was reviewed, synthesized, and mapped onto the proposed multi-systemic framework. Key Content and Findings: The current review considers existing literature across three proposed dimensions of resilience: contexts of risk exposure, protective and promotive factors/processes, and desired outcomes. Review of each dimension includes consideration of selected existing literature to explain what is known about each dimension currently, as well as to propose additional potential future areas to broaden understanding. Specific key takeaways include: (I) understanding risk exposure in young people with IBD requires consideration of disease-specific, demographic, and sociocultural factors; (II) protective and promotive factors and processes for these young people span individual, familial, peer, school, and community levels; and (III) desired outcomes encompass both the absence of negative and the presence of positive indicators. Conclusions: A multisystemic approach to the study of resilience in young people with IBD may not only clarify current gaps in the field, but also allow for additional future considerations to best understand how and for whom outcomes characterized as resilient may occur in this population.

The role of arousal in maintaining the relationship between insomnia and gastrointestinal conditions.

The relationship between gastrointestinal (GI) conditions and sleep disturbance has been well established. With a higher-than-average prevalence of sleep disturbance in individuals with GI conditions, it is imperative to better understand the maintaining factors driving this comorbidity. Although there are separate, ongoing investigations into both the biological mechanisms and interventions for the sleep and GI relationship, there is a considerable need to further specify common and mutually influential pathways. In our review, we highlight arousal as both a unifying feature of insomnia and various GI conditions as well as a possible mechanism for action for the bidirectional relationship. This review aims to summarize the relationship between arousal, insomnia, and GI conditions, specifically examining sources of arousal across four broad domains: psychosocial factors, physical health factors, daily living factors, and sociocultural factors. Online databases, including PubMed, PsychInfo, and Google Scholar, were searched for full-text English language articles focused on patients with insomnia and/or GI conditions and involving mental health, physical comorbidities, and social factors. Understanding the nature of this bidirectional relationship between sleep and GI through the lens of arousal as a common mechanism will lend itself to using a multidisciplinary approach to treatment and care.

Acceptance and commitment therapy for the treatment of irritable bowel syndrome and inflammatory bowel disease: a narrative review.

Background and Objective: Cognitive behavioral therapy (CBT) is a common treatment modality for patients with irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). CBT may not be a good fit for all patients and some may instead benefit from an acceptance and commitment therapy (ACT) approach. This narrative review presents evidence for the use of ACT in adult patients with IBS or IBD. The authors also suggest instances in which patients with IBS or IBD may benefit from ACT and discuss future directions of research. Methods: Between August 2023 and January 2024, databases such as Google Scholar, institutional libraries, and PubMed were used to review the literature on ACT in patients with IBS and IBD. A variety of search terms were included. Non-English, pediatric, and studies that did not employ a full ACT protocol were excluded. Key Content and Findings: ACT for IBS studies typically utilized a self-help book or a one-day workshop intervention, with results indicating reductions in IBS and mood symptoms and improvements in quality of life. Within IBD, three randomized controlled trials (RCTs) tested the impact of ACT, two of which found reductions in stress, depression, and anxiety symptoms. Conclusions: Despite the limited number of studies testing a full ACT protocol in patient populations with IBS or IBD, results indicate potential efficacy in managing not only symptoms, but also facets of quality of life. Future studies should utilize robust experimental designs and comprehensively test the effectiveness of ACT in IBS and IBD patient populations with both process and outcome measures.

Keratoconus and inflammatory bowel disease: mendelian randomization.

Background: Keratoconus is a diseased corneal dilation of unknown etiology. Studies have shown that inflammation may play a role in keratoconus. Inflammatory enteritis (IBD), including ulcerative colitis (UC), is a chronic, systemic inflammatory disease. We used Mendelian randomization to assess the causal relationship among IBD, UC and keratoconus. Methods: The instrumental variable of IBD and UC was selected, the information of the instrumental variable in keratoconus outcome was extracted, and the causal relationship was assessed by the inverse variance weighted method by primary analysis, and its relevant sensitivity analysis. Results: A causal relationship between IBD and keratoconus was observed significantly (P = 0.017, OR = 1.21, 95% CI = 1.03-1.41), and same as to UC and keratoconus (P = 0.038, OR = 1.25, 95% CI = 1.01-1.54). Conclusion: IBD may play a causal role in the development of keratoconus, but the mechanism needs to be further elucidated.

Predictors of improvement in disease activity in childhood and adolescent Crohn's disease: an analysis of age, localization, initial severity and drug therapy - data from the Saxon Registry for Inflammatory Bowel Disease in Children in Germany (2000-2014).

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants.Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.

Docosahexaenoic acid (DHA) alleviates inflammation and damage induced by experimental colitis.

PURPOSE: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic gastrointestinal disorders associated with significant morbidity and complications. This study investigates the therapeutic potential of docosahexaenoic acid (DHA) in a trinitrobenzene sulfonic acid (TNBS) induced colitis model, focusing on inflammation, oxidative stress, and intestinal membrane permeability. METHODS: Wistar albino rats were divided into Control, Colitis, and Colitis + DHA groups (n = 8-10/group). The Colitis and Colitis + DHA groups received TNBS intrarectally, while the Control group received saline. DHA (600 mg/kg/day) or saline was administered via gavage for six weeks. Macroscopic and microscopic evaluations of colon tissues were conducted. Parameters including occludin and ZO-1 expressions, myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels were measured in colon tissues. RESULTS: Colitis induction led to significantly higher macroscopic and microscopic damage scores, elevated TOS levels, reduced occludin and ZO-1 intensity, decreased mucosal thickness, and TAS levels compared to the Control group (p < 0.001). DHA administration significantly ameliorated these parameters (p < 0.001). MPO, MDA, TNF-α, and IL-6 levels were elevated in the Colitis group but significantly reduced in the DHA-treated group (p < 0.001 for MPO, MDA; p < 0.05 for TNF-α and IL-6). CONCLUSION: DHA demonstrated antioxidant and anti-inflammatory effects by reducing reactive oxygen species production, enhancing TAS capacity, preserving GSH content, decreasing proinflammatory cytokine levels, preventing neutrophil infiltration, reducing shedding in colon epithelium, and improving gland structure and mucosal membrane integrity. DHA also upregulated the expressions of occludin and ZO-1, critical for barrier function. Thus, DHA administration may offer a therapeutic strategy or supplement to mitigate colitis-induced adverse effects.

Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions.

Chronic pain is a debilitating symptom with a significant negative impact on the quality of life and socioeconomic status, particularly among adults and the elderly. Major Depressive Disorder (MDD) stands out as one of the most important comorbid disorders accompanying chronic pain. The kynurenine pathway serves as the primary route for tryptophan degradation and holds critical significance in various biological processes, including the regulation of neurotransmitters, immune responses, cancer development, metabolism, and inflammation. This review encompasses key research studies related to the kynurenine pathway in the context of headache, neuropathic pain, gastrointestinal disorders, fibromyalgia, chronic fatigue syndrome, and MDD. Various metabolites produced in the kynurenine pathway, such as kynurenic acid and quinolinic acid, exhibit neuroprotective and neurotoxic effects, respectively. Recent studies have highlighted the significant involvement of kynurenine and its metabolites in the pathophysiology of pain. Moreover, pharmacological interventions targeting the regulation of the kynurenine pathway have shown therapeutic promise in pain management. Understanding the underlying mechanisms of this pathway presents an opportunity for developing personalized, innovative, and non-opioid approaches to pain treatment. Therefore, this narrative review explores the role of the kynurenine pathway in various chronic pain disorders and its association with depression and chronic pain.

Multidisciplinary Perspectives on Medical Decision-Making for Ostomy Surgery in Pediatric IBD: Themes from Focus Groups.

Pediatric Inflammatory Bowel Disease (IBD) is a chronic illness where patients may undergo ostomy surgery. Medical decision-making (MDM) for ostomy surgery is complex for patients/families and multidisciplinary healthcare professionals (HCPs) alike, with current uncertainty about how multidisciplinary HCPs think about ostomy care to inform future interventions to facilitate equitable multidisciplinary care for patients. This study sought to understand pediatric IBD multidisciplinary HCPs' perceptions regarding ostomy-related MDM and education. Multidisciplinary HCPs (e.g., gastroenterology medical providers, social workers, surgeons, and ostomy nurses) participated in semi-structured focus groups. Focus group data underwent qualitative analysis to identify themes. Three multidisciplinary focus groups were conducted, with n = 12 participants across all groups. Qualitative analysis identified three main themes, including (1) HCP perceptions of ostomies, (2) Patient/family-related factors, and (3) Professional roles and collaboration challenges. Ostomy surgery in pediatric IBD requires complex multidisciplinary MDM and education. Perspectives of multidisciplinary HCPs identified patient, HCP, and systems factors that may impact MDM for ostomy surgery. This work highlights nuances in MDM and education in IBD, and the critical role of ongoing research and improved standardized processes to coordinate multidisciplinary ostomy-related MDM and education in this population.

Engineering a Novel Probiotic Toolkit in Escherichia coli Nissle 1917 for Sensing and Mitigating Gut Inflammatory Diseases.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation with no cure and limited treatment options that often have systemic side effects. In this study, we developed a target-specific system to potentially treat IBD by engineering the probiotic bacterium Escherichia coli Nissle 1917 (EcN). Our modular system comprises three components: a transcription factor-based sensor (NorR) capable of detecting the inflammation biomarker nitric oxide (NO), a type 1 hemolysin secretion system, and a therapeutic cargo consisting of a library of humanized anti-TNFα nanobodies. Despite a reduction in sensitivity, our system demonstrated a concentration-dependent response to NO, successfully secreting functional nanobodies with binding affinities comparable to the commonly used drug Adalimumab, as confirmed by enzyme-linked immunosorbent assay and in vitro assays. This newly validated nanobody library expands EcN therapeutic capabilities. The adopted secretion system, also characterized for the first time in EcN, can be further adapted as a platform for screening and purifying proteins of interest. Additionally, we provided a mathematical framework to assess critical parameters in engineering probiotic systems, including the production and diffusion of relevant molecules, bacterial colonization rates, and particle interactions. This integrated approach expands the synthetic biology toolbox for EcN-based therapies, providing novel parts, circuits, and a model for tunable responses at inflammatory hotspots.

Oat Beta-Glucan Dietary Intervention on Antioxidant Defense Parameters, Inflammatory Response and Angiotensin Signaling in the Testes of Rats with TNBS-Induced Colitis.

Male infertility represents a significant public health concern. There is a negative impact of inflammatory bowel diseases (IBDs) on the male reproductive system. The aim of this study was to investigate whether oat beta-glucan (OBG) with different molar mass can modulate parameters of antioxidant defense and inflammatory response in the testes of adult Sprague-Dawley rats with TNBS-induced colitis and whether the OBG intervention can modulate the inflammatory response in association with the RAS system. Results: higher testicular superoxide dismutase (SOD), glutathione reductase (GR) activities and glutathione (GSH) concentration, and lower testosterone (T) level and glutathione peroxidase (GPx) activity, were observed in rats with colitis than in healthy control ones. TNBS-induced colitis resulted in decreased the angiotensin 1-7 (ANG 1-7) level in the testes of rats fed with low-molar mass OBG compared to control animals. Conclusions: although colitis induced moderate pro-oxidant changes in the gonads, it seems plausible that dietary intervention with different fractions of oat beta-glucans mass may support the maintenance of reproductive homeostasis via the stimulation of the local antioxidant defense system.

Design, Synthesis, in Vitro and in Vivo Biological Evaluation of Pterostilbene Derivatives for the Treatment of Inflammatory Bowel Disease.

The aberrant activation of NLRP3 inflammasomes is intricately linked to various inflammatory diseases. In this study, we present the discovery and optimization of a series of NLRP3 inflammasome inhibitors based on the pterostilbene skeleton. All compounds underwent screening to evaluate their inhibitory effects on LPS/Nigericin-induced IL-1ß secretion and anti-cellular pyroptosis. Most compounds exhibit good biological activity and cellular safety, with compound D20 showing the most prominent activity. Preliminary mechanism studies suggest that compound D20 may affect the assembly of NLRP3 inflammasomes by targeting the NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasomes. The in vivo anti-inflammatory activity demonstrated significant therapeutic effect of compound D20 on DSS-induced acute colitis model in mice. This work has important reference significance for the development of drugs targeting NLRP3 inflammasomes.

Unraveling Cross-Organ Impacts of Airborne Pollutants: A Multiomics Study on Respiratory Exposure and Gastrointestinal Health.

Poor air quality is increasingly linked to gastrointestinal diseases, suggesting a potential correlation with human intestine health. However, this relationship remains largely unexplored due to limited research. This study used a controlled mouse model exposed to cooking oil fumes (COFs) and metagenomics, transcriptomics, and metabolomics to elucidate interactions between intestine microbiota and host metabolism under environmental stress. Our findings reveal that short-term COF inhalation induces pulmonary inflammation within 3 days and leads to gastrointestinal disturbances, elucidating a pathway connecting respiratory exposure to intestinal dysfunction. The exposure intensity significantly correlates with changes in intestinal tissue integrity, microbial composition, and metabolic function. Extended exposure of 7 days disrupts intestine microbiota and alters tryptophan metabolism, with further changes observed after 14 days, highlighting an adaptive response. These results highlight the vulnerability of intestinal health to airborne pollutants and suggest a pathway through which inhaled pollutants may affect distant organ systems.

Comparative Efficacy of Biologics and Small Molecule Therapies in Improving Patient-Reported Outcomes in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.

BACKGROUND: Ulcerative colitis (UC) is a chronic disorder with a considerable negative impact on health-related quality of life (HRQoL), which has been recently recognized as an important treatment target. The purpose of this study is to compare the efficacy of different biologics and small molecule therapies in achieving better patient-reported outcomes and HRQoL in patients with UC. METHODS: We performed a systematic review and network meta-analysis of the EMBASE, MEDLINE, and Cochrane Central databases from inception until February 1, 2024. The primary endpoint was clinical remission in the patient-reported outcome (PRO-2) score in UC patients who were treated with different biologics or small molecules during induction and maintenance phases. PRO-2 score is the sum of both stool frequency and rectal bleeding subscores. The secondary outcome was improvement of HRQoL defined as an increase in Inflammatory Bowel Disease Questionnaire score of ≥16 points from baseline or any change in total score from baseline. A random effects model was used, and outcomes were reported as odds ratio with 95% confidence interval. Interventions were ranked per the SUCRA (surface under the cumulative ranking curve) score. RESULTS: A total of 54 studies were included in the primary outcome analysis and 15 studies were included in the secondary outcome analysis. The primary analysis showed that during the induction phase all of included drugs were better than placebo in improving the PRO-2 score. Interestingly, upadacitinib was found to be superior to most medications in improving PRO-2 scores. The secondary analysis showed that guselkumab ranked first in the improvement of the Inflammatory Bowel Disease Questionnaire score, followed by upadacitinib during the induction phase. CONCLUSION: Upadacitinib ranked first in PRO-2 clinical remission during the induction and maintenance phases. Guselkumab, mirikizumab, tofacitinib, and upadacitinib were the only novel medications that were superior to placebo in improving HRQoL in UC, with guselkumab ranking the highest, followed by tofacitinib and upadacitinib. During maintenance of remission, tofacitinib ranked highest in improving HRQoL.

Patient-reported outcome (PRO-2) and disease impact on health-related quality of life (HRQoL) have been recognized as important treatment targets in ulcerative colitis. In this systematic review and network meta-analysis, we compared different biologics and small molecules in achieving these outcomes. We found that upadacitinib ranked first in PRO-2 clinical remission during induction and maintenance phases. Guselkumab, tofacitinib, and upadacitinib were the only novel medications that were superior to placebo in improving HRQoL during induction in ulcerative colitis, with guselkumab ranking the highest, followed by tofacitinib and upadacitinib. During maintenance of remission, tofacitinib ranked highest in improving HRQoL.

Development and Validation of a Mobile-Centered Digital Health Readiness Scale (mDiHERS): Health Literacy and Equity Scale.

BACKGROUND: There has been a rapid expansion of digital health care services, making the need for measuring and improving digital health readiness a priority. In response, our study team developed the Mobile-Centered Digital Health Readiness: Health Literacy and Equity Scale (mDiHERS) to measure digital health readiness. OBJECTIVE: We aim to develop and validate a scale that assesses digital health readiness, encompassing literacy and equity, and to ensure the effective use of mobile-centered digital health services. METHODS: This study was conducted from October 2021 to October 2022 to develop and validate the mDiHERS. Participants included patients with inflammatory bowel disease, which is a chronic condition requiring continuous management, and experts in medical and nursing informatics. The scale development involved a literature review, focus group interviews, and content validity evaluations. A total of 440 patients with inflammatory bowel disease were recruited for the validation phase, with 403 completing the survey. The scale's validity and reliability were assessed through exploratory factor analysis and Cronbach α. The scale was translated into English by translators and bilingual and native researchers, ensuring its applicability in diverse settings. RESULTS: The mDiHERS consists of 36 items across 6 domains, with a 5-point Likert scale for responses. The validation process confirmed the scale's construct validity, with 4 factors explaining 65.05% of the total variance. The scale's reliability was established with Cronbach α values ranging from 0.84 to 0.91. The scale's development considered the technical proficiency necessary for engaging with health mobile apps and devices, reflecting the importance of subjective confidence and objective skills in digital health literacy. CONCLUSIONS: The mDiHERS is a validated tool for measuring patients' readiness and ability to use digital health services. The mDiHERS assesses user characteristics, digital accessibility, literacy, and equity to contribute to the effective use of digital health services and improve accessibility. The development and validation of the mDiHERS emphasize the importance of confidence and competence in managing health digitally. Continuous improvements are necessary to ensure that all patients can benefit from digital health care.

WNT2B high­expressed fibroblasts induce the fibrosis of IBD by promoting NK cells secreting IL-33.

Fibrosis is an important pathological change in inflammatory bowel disease (IBD), but the mechanism has yet to be elucidated. WNT2B high­expressed fibroblasts are enriched in IBD intestinal tissues, although the precise function of this group of fibroblasts remains unclear. This study investigated whether WNT2B high­expressed fibroblasts aggravated intestinal tissue damage and fibrosis. Our study provides evidence that WNT2B high­expressed fibroblasts and NK cells were enriched in colitis tissue of patients with IBD. WNT2B high­expressed fibroblasts secreted wnt2b, which bound to FZD4 on NK cells and activated the NF-κB and STAT3 pathways to enhance IL-33 expression. TCF4, a downstream component of the WNT/ß-catenin pathway, bound to p65 and promoted binding to IL-33 promoter. Furthermore, Salinomycin, an inhibitor of the WNT/ß-catenin pathway, inhibited IL-33 secretion in colitis, thereby reducing intestinal inflammation.Knocking down WNT2B reduces NK cell infiltration and IL-33 secretion in colitis, and reduce intestinal inflammation and fibrosis. In conclusion, WNT2B high­expressed fibroblasts activate NK cells by secreting wnt2b, which activates the WNT/ß-catenin and NF-κB pathways to promote IL-33 expression and secretion, potentially culminating in the induction of colonic fibrosis in IBD. KEY MESSAGES: WNT2B high-expressed fibroblasts and NK cells are enriched in colitis tissue, promoting NK cells secreting IL-33. Wnt2b activates NF-κB and STAT3 pathways promotes IL-33 expression by activating p65 and not STAT3. syndrome TCF4 binds to p65 and upregulates the NF- κB pathway. Salinomycin reduces NK cell infiltration and IL-33 secretion in colitis. Knocking down WNT2B mitigates inflammation and fibrosis in chronic colitis.

Ultrasound of the bowel with a focus on IBD: the new best practice.

Inflammatory Bowel Disease (IBD) is a lifelong chronic disease affecting any part of the gastrointestinal tract with a predilection for the terminal ileum. IBD patients require repeat imaging throughout the course of their disease, necessitating a safe, noninvasive, available, and repeatable method. Imaging is required at diagnosis, routine surveillance, and acute exacerbation of disease. Ultrasound imaging meets these demands with a high degree of accuracy and wide patient acceptance. Ultrasound provides high-resolution imaging and is excellent for detailed evaluation of the bowel wall and surrounding soft tissues. Regular greyscale bowel evaluation and color Doppler imaging now have accepted standards for evaluating disease activity based on wall thickness, perienteric inflammatory fat, and blood flow, which is invaluable in staging and grading disease. High-resolution dynamic real-time imaging on ultrasound has the ability to show functional as well as morphologic detail, including dysfunctional peristalsis associated with bowel stricture and incomplete mechanical bowel obstruction. Fibrostenotic and penetrating complications of IBD may be associated with an acute or chronic presentation that is easily assessed using ultrasound. Newer software technologies for ultrasound, including Contrast-Enhanced ultrasound and Shear wave elastography, have transformed ultrasound from a basic preliminary imaging technique into a highly sophisticated modality that is now competitive with CT and MR enterography for managing IBD patients. Our long experience with ultrasound of the bowel suggests that the new best practice would include ultrasound as the first test for evaluation of the bowel at any stage of the disease.

Targeting microbial pathogenic mechanisms as a novel therapeutic strategy in IBD.

BACKGROUND: Current therapy for patients suffering from inflammatory bowel diseases (IBD) is focused on inflammatory mechanisms exclusively and not the dysbiotic microbiota, despite growing evidence implicating a role for intestinal microbes in disease. MAIN BODY: Ongoing research into the intestinal microbiota of IBD patients, using new technologies and/or deeper application of existing ones, has identified a number of microorganisms whose properties and behaviors warrant consideration as causative factors in disease. Such studies have implicated both bacteria and fungi in the pathogenesis of disease. Some of these organisms manifest mechanisms that should be amenable to therapeutic intervention via either conventional or novel drug discovery platforms. Of particular note is a deeper characterization of microbial derived proteases and their destructive potential. CONCLUSION: Given the steady progress on the mechanistic role of the microbiota in inflammatory diseases, it is reasonable to anticipate a future in which therapeutics targeting microbial derived pathogenic factors play an important role in improving the lives of IBD patients.

A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis.

Hepatic factors secreted by the liver promote homeostasis and are pivotal for maintaining the liver-gut axis. Bile acid metabolism is one such example wherein, bile acid synthesis occurs in the liver and its biotransformation happens in the intestine. Dysfunctional interactions between the liver and the intestine stimulate varied pathological outcomes through its bidirectional portal communication. Indeed, aberrant bile acid metabolism has been reported in inflammatory bowel disease (IBD). However, the molecular mechanisms underlying these crosstalks that perpetuate intestinal permeability and inflammation remain obscure. Here, we identify a novel hepatic gene program regulated by Rela and Stat3 that accentuates the inflammation in an acute experimental colitis model. Hepatocyte-specific ablation of Rela and Stat3 reduces the levels of primary bile acids in both the liver and the gut and shows a restricted colitogenic phenotype. On supplementation of chenodeoxycholic acid (CDCA), knock-out mice exhibit enhanced colitis-induced alterations. This study provides persuasive evidence for the development of multi-organ strategies for treating IBD and identifies a hepatocyte-specific Rela-Stat3 network as a promising therapeutic target.

The Challenge of IBD-Related Arthritis Screening Questionnaires in Early and Predominantly Entheseal Phenotypes.

INTRODUCTION: Inflammatory bowel disease (IBD)-related arthritis is recognized as the most prevalent extraintestinal manifestation (EIM) of IBD. The objective of this study was to determine the prevalence and characteristics of undiagnosed IBD-related arthritis and to compare two screening questionnaires, DETection of Arthritis in Inflammatory boweL diseases (DETAIL) and IBd Identification of Spondyloarthritis Questionnaire (IBIS-q), for early disease detection. METHODS: Between April and October 2023, both the DETAIL and IBIS-q questionnaires were administered to consecutive IBD outpatients visiting the University Hospital of Udine, Italy. During routine gastroenterology evaluations, patients aged > 18 years with Crohn's disease (CD) or ulcerative colitis (UC) were requested to complete both questionnaires. Subsequently, all patients who completed the questionnaires underwent a blinded rheumatological evaluation within 2 weeks. Patients with a previous diagnosis of IBD-related SpA were then excluded. RESULTS: Overall, 203 patients were enrolled, of whom 26 were excluded because of a prior diagnosis of inflammatory arthritis. Among the remaining 177 patients, 10/177 (5.6%) received a new diagnosis of IBD-related arthritis. The median duration of symptoms before diagnosis was 4 (IQR 1.8-10.5) months. Imaging-confirmed enthesitis was the predominant pattern in 8 out 10 cases (80%, with 8 out 8 lacking concomitant peripheral arthritis), axial involvement in 1 out 10 cases (10%), and peripheral arthritis in 1 out 10 cases (10%). The DETAIL questionnaire exhibited higher specificity, but lower sensitivity compared to the IBIS-q, with a sensitivity of 40.0% (12.2-73.8) and specificity of 84.4% (78.0-89.6) versus a sensitivity of 70.0% (34.8-93.3) and specificity of 74.3% (66.9-80.7). Both questionnaires performed less effectively than in other studies. CONCLUSION: This study highlights a significant proportion of undiagnosed IBD-related arthritis (5.6%). Enthesitis emerged as the predominant pattern of newly diagnosed arthritis in our cohort, likely due to the recent onset of symptoms. Our study underscores the importance of entheseal involvement in early IBD-related arthritis and the importance of incorporating entheseal involvement into screening questionnaires.