The Role of Viruses in the Pathogenesis of Immune-Mediated Gastro-Intestinal Diseases.

Immune-mediated gastrointestinal (GI) diseases, including achalasia, celiac disease, and inflammatory bowel diseases, pose significant challenges in diagnosis and management due to their complex etiology and diverse clinical manifestations. While genetic predispositions and environmental factors have been extensively studied in the context of these conditions, the role of viral infections and virome dysbiosis remains a subject of growing interest. This review aims to elucidate the involvement of viral infections in the pathogenesis of immune-mediated GI diseases, focusing on achalasia and celiac disease, as well as the virome dysbiosis in IBD. Recent evidence suggests that viral pathogens, ranging from common respiratory viruses to enteroviruses and herpesviruses, may trigger or exacerbate achalasia and celiac disease by disrupting immune homeostasis in the GI tract. Furthermore, alterations in the microbiota and, specifically, in the virome composition and viral-host interactions have been implicated in perpetuating chronic intestinal inflammation in IBD. By synthesizing current knowledge on viral contributions to immune-mediated GI diseases, this review aims to provide insights into the complex interplay between viral infections, host genetics, and virome dysbiosis, shedding light on novel therapeutic strategies aimed at mitigating the burden of these debilitating conditions on patients' health and quality of life.

Dysregulated serum concentrations of fat-soluble vitamins in dogs with chronic enteropathy.

BACKGROUND: In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat-soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat-soluble vitamins (FSVs) is lacking. OBJECTIVES: Determine the serum concentrations of retinol, vitamin D, and α-tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations. ANIMALS: Eighteen client-owned dogs with CE and 33 healthy dogs. METHODS: Serum 25-hydroxyvitamin D (25[OH]D), serum retinol and α-tocopherol concentrations were compared between groups. Correlations and multiple regression modeling were used to examine the relationship between serum 25(OH)D, retinol, and α-tocopherol concentrations and clinical and clinicopathological variables. RESULTS: Dogs with low serum albumin concentrations were more likely to have lower 25(OH)D concentrations than dogs with normal serum albumin concentration. Dogs with CE had higher serum concentrations of retinol, and variable α-tocopherol concentrations. The cause of these dysregulated vitamin concentrations is unclear and requires further study. CONCLUSION AND CLINICAL IMPORTANCE: Dogs with severe forms of CE should be monitored for decreased concentrations of 25(OH)D. Additional studies are needed to evaluate the clinical relevance and the possible benefit of vitamin D supplementation in these patients.

Thirty-day outcomes of non-emergent colectomy for inflammatory bowel disease in patients with chronic obstructive pulmonary disease.

BACKGROUND: Inflammatory bowel disease (IBD) can have significant colonic involvement and carries a long-term risk of surgical resection. Chronic obstructive pulmonary disease (COPD) and IBD share multiple inflammatory pathways, suggesting a bidirectional relationship through proposed pulmonary-intestinal cross-talk. This study aimed to examine the association between COPD and 30-day outcomes following non-emergent colectomies for IBD. METHODS: Patients with IBD as the primary indication for colectomy were selected from National Surgical Quality Improvement Program (NSQIP) colectomy database 2012-2022. Emergency colectomy cases were excluded. A 1:3 propensity-score matching was used to balance the preoperative characteristics of COPD and non-COPD patients. Thirty-day postoperative outcomes were compared. RESULTS: Among 25,285 patients who underwent colectomy for IBD, 365 (1.44 %) had COPD. Patients with COPD were older and had more comorbidities. After propensity-score matching, all COPD patients were matched to 1,095 patients without COPD. COPD and non-COPD patients had comparable 30-day mortality (3.29 % vs 2.19 %, p = 0.25). However, COPD patients had higher pulmonary complications (14.79 % vs 7.21 %, p < 0.01) attributed to pneumonia (10.14 % vs 4.02 %, p < 0.01), sepsis (12.88 % vs 8.68 %, p = 0.02), prolonged postoperative nothing by mouth (NPO) or nasogastric tube (NGT) use (28.22 % vs 22.10 %, p = 0.02), discharge not to home (40.28 % vs 34.02 %, p = 0.04), and longer length of stay (p = 0.01). CONCLUSION: Therefore, given their mortality rates, colectomy is an effective treatment for IBD patients with concurrent COPD, while their postoperative care should include close monitoring of pulmonary symptoms and timely interventions to prevent further complications. Future research should explore the long-term prognosis of COPD patients after colectomy for IBD.

Mirikizumab: A promising breakthrough in Crohn's disease treatment.

Introduction: Crohn's disease (CD) is a chronic, progressive inflammatory bowel disorder characterized by persistent inflammation and noncontiguous "skip lesions" throughout the gastrointestinal tract. With a prevalence of 100-300 cases per 100,000 individuals, CD is most common in Western Europe and North America. Symptoms include abdominal pain, diarrhea, fever, weight loss, and anemia, with severe cases leading to complications such as perianal abscesses and cutaneous fistulas. Treatment involves pharmaceutical interventions, bowel rest, and sometimes surgery, with biological therapies like ustekinumab and mirikizumab gaining prominence. Clinical Trials: The VIVID-1 trial assessed mirikizumab in patients with moderately to severely active CD. By Week 12, mirikizumab significantly outperformed placebo in clinical response (45.4% vs. 19.6%, p < 0.000001). By Week 52, it showed higher clinical remission rates (54.1% vs. 19.6%) and demonstrated non-inferiority to ustekinumab in clinical remission (p = 0.51). The SEQUENCE study compared risankizumab to ustekinumab, with risankizumab showing superior reductions in inflammatory markers and higher biologic remission rates at Weeks 8, 24, and 48. Both treatments had similar safety profiles, with common adverse events including COVID-19, anemia, and headache. Conclusion: Mirikizumab, based on the VIVID-1 trial outcomes, is a promising addition to CD therapy. It demonstrated significant clinical responses and remission rates, warranting further research on its long-term efficacy and safety. Updating professional guidelines and addressing affordability will ensure broader access and improved management of CD.

Obinutuzumab-Induced Inflammatory Bowel Disease-Like Pancolitis: A First Case Report.

Introduction: Obinutuzumab is a type II anti-CD20 monoclonal antibody associated with a higher rate of toxicity when compared to rituximab. Gastrointestinal side-effects have been reported but data is still sparse. Case Presentation: A 47-year-old female with medical history of stage IV follicular non-Hodgkin lymphoma under chemotherapy presented with chronic bloody diarrhea and iron deficiency anemia. Endoscopic and histologic features resembled inflammatory bowel disease (IBD), imposing a thorough differential diagnosis. The diagnosis of obinutuzumab-induced pancolitis was made and the drug was suspended with subsequent clinical improvement. Conclusion: This is the first case report of obinutuzumab-induced pancolitis. The challenging differential diagnosis of IBD required a multidisciplinary approach with subsequent outcome and management implications.

Introdução: Obinutuzumab é um anticorpo monoclonal anti-CD20 tipo II, com aparente maior taxa de toxicidade relativamente ao rituximab. Alguns efeitos adversos gastrointestinais têm sido reportados, no entanto, a evidência científica mantém-se escassa. Caso Clínico: Mulher de 47 anos, com antecedentes de linfoma não-Hodgkin folicular estádio IV sob quimioterapia, apresenta-se com diarreia crónica sanguinolenta e anemia ferropénica. Os achados endoscópicos e histológicos assemelham-se a uma doença inflamatória intestinal (DII), impondo um diagnóstico diferencial exaustivo. Foi diagnosticada com uma pancolite induzida por obinutuzumab, tendo este sido suspenso, com melhoria clínica subsequente. Conclusão: Este é o primeiro caso documentado de pancolite induzida por obinutuzumab. A apresentação com aspetos sugestivos de DII obrigou a uma abordagem holística e multidisciplinar com implicações na abordagem e seguimento da doente.

Anti-TNFα in inflammatory bowel disease: from originators to biosimilars.

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review.

EGCG drives gut microbial remodeling-induced epithelial GPR43 activation to lessen Th1 polarization in colitis.

Modulation of immune microenvironment is critical for inflammatory bowel disease (IBD) intervention. Epigallocatechin gallate (EGCG), as a natural low toxicity product, has shown promise in treating IBD. However, whether and how EGCG regulates the intestinal microenvironment is not fully understood. Here we report that EGCG lessens colitis by orchestrating Th1 polarization and self-amplification in a novel manner that required multilevel-regulated intestinal microecosystem. Mechanistically, EGCG activates GPR43 on IEC to inhibit Th1 polarization dependently of short chain fatty acid (SCFA)-producing gut microbiota. Inhibition of GPR43 activity weakens the protective effects of EGCG on colitis development. Moreover, we confirm that fecal SCFAs and/or intestinal GPR43 are limited in patients with colitis and are correlated with Th1 cell number. Taken together, our study reveals an intestinal microenvironment-dependent immunoregulatory effects of EGCG in treating IBD and provides insight into mechanisms of EGCG-based novel immunotherapeutic strategies for IBD.

Determination of codon pattern and evolutionary forces acting on genes linked to inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract. The present study attempted to understand the codon usage preferences in genes associated with IBD progression. Compositional analysis, codon usage bias (CUB), Relative synonymous codon usage (RSCU), RNA structure, and expression analysis were performed to obtain a comprehensive picture of codon usage in IBD genes. Compositional analysis of 62 IBD-associated genes revealed that G and T are the most and least abundant nucleotides, respectively. ApG, CpA, and TpG dinucleotides were overrepresented or randomly used, while ApC, CpG, GpT, and TpA dinucleotides were either underrepresented or randomly used in genes related to IBD. The codons influencing the codon usage the most in IBD genes were CGC and AGG. A comparison of codon usage between IBD, and pancreatitis (non-IBD inflammatory disease) indicated that only codon CTG codon usage was significantly different between IBD and pancreatitis. At the same time, there were codons ATA, ACA, CGT, CAA, GTA, CCT, ATT, GCT, CGG, TTG, and CAG for whom codon usage was significantly different for IBD and housekeeping gene sets. The results suggest similar codon usage in at least two inflammatory disorders, IBD and pancreatitis. The analysis helps understand the codon biology, factors affecting gene expression of IBD-associated genes, and the evolution of these genes. The study helps reveal the molecular patterns associated with IBD.

Modified montmorillonite armed probiotics with enhanced on-site mucus-depleted intestinal colonization and H2S scavenging for colitis treatment.

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H2S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H2S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases.

Matrix metalloproteinase -responsive hydrogels with tunable retention for on-demand therapy of inflammatory bowel disease.

Therapeutic options for addressing inflammatory bowel disease (IBD) include the administration of an enema to reduce intestinal inflammation and alleviate associated symptoms. However, uncontrollable retention of enemas in the intestinal tract has posed a long-term challenge for improving their therapeutic efficacy and safety. Herein we have developed a protease-labile hydrogel system as an on-demand enema vehicle with tunable degradation and drug release rates in response to varying matrix metalloproteinase-9 (MMP-9) expression. The system, composed of three tailored hydrogel networks, is crosslinked by poly (ethylene glycol) (PEG) with 2-, 4- and 8-arms through dynamic hydrazone bonds to confer injectability and generate varying network connectivity. The retention time of the hydrogels can be tuned from 12-36 hours in the intestine due to their different degradation behaviors induced by MMP-9. The drug-releasing rate of the hydrogels can be controlled from 0.0003mg/h to 0.278mg/h. In addition, injection of such hydrogels in vivo resulted in significant differences in therapeutic effects including MMP-9 consumption, colon tissue repair, reduced collagen deposition, and decreased macrophage cells, for treating a mouse model of acute colitis. Among them, GP-8/5-ASA exhibits the best performance. This study validates the effectiveness of the tailored design of hydrogel architecture in response to pathological microenvironment cues, representing a promising strategy for on-demand therapy of IBD. STATEMENT OF SIGNIFICANCE: The uncontrollable retention of enemas at the delivery site poses a long-term challenge for improving therapeutic efficacy in IBD patients. MMP-9 is highly expressed in IBD and correlates with disease severity. Therefore, an MMP-9-responsive GP hydrogel system was developed as an enema by linking multi-armed PEG and gelatin through hydrazone bonds. Thisforms a dynamic hydrogel characterized by in situ gelation, injectability, enhanced bio-adhesion, biocompatibility, controlled retention time, and regulated drug release. GP hydrogels encapsulating 5-ASA significantly improved the intestinal phenotype of acute IBD and demonstrated notable therapeutic differences with increasing PEG arms. This method represents a promising on-demand IBD therapy strategy and provides insights into treating diseases of varying severities using endogenous stimulus-responsive drug delivery systems.

Exploration of Therapeutic Strategies of Herbal Prescriptions for Carbuncle Treatment to Suggest Modern Approaches to Inflammatory Bowel Disease: Cluster and Network Analyses of the Book «Liu Juan Zi Gui Yi Fang¼.

Inflammatory bowel disease (IBD) treatments in East Asian traditional medicine (EATM) originate from principles for treating abscesses and carbuncles. Understanding the therapeutic principles of Liu Juan Zi Gui Yi Fang (GYF) is essential for optimizing EATM treatment strategies for IBD, but quantitative analysis is lacking. This study aims to extract quantitative information on therapeutic strategies from GYF and present the EATM conceptual framework for IBD treatment. Oral prescriptions for carbuncles were selected, and their constituent herbs and indications were standardized and tokenized for analysis. An EATM expert group classified prescriptions based on the similarity of herbs and indications. Hierarchical and k-means cluster analyses were performed based on herb similarity. The herb-indication (H-I) network for all prescriptions was constructed. Additionally, H-I subnetworks based on the expert group's classifications and the k-means clustering results were constructed and compared to identify treatment goals and the herbs used for each goal. The results showed that the treatment focused on abscess status, wound healing, and patient's recovery capacity, with 'fever' and 'deficiency' as the main indications addressed by tonifying and anti-inflammatory herbs. The therapeutic principles identified in this study can serve as a foundation for developing future herbal intervention units. Further preclinical and clinical research is needed to validate these findings.

Preoperative optimization: Review on nutritional assessment and strategies in IBD.

Inflammatory bowel diseases (IBD), encompassing conditions like Crohn's disease and ulcerative colitis, present multifaceted challenges requiring a comprehensive management approach. Patients often necessitate a combination of medical therapy, surgical interventions, and nutritional support. Despite advancements in medical and dietary therapies, the prevalence of surgery remains high among the IBD population, alongside the persistent risk of malnutrition. Preoperative nutritional optimization has thus become a critical element in the perioperative pathway, given its association with improved surgical outcomes. However, standardized protocols for preoperative optimization of IBD patients are lacking, and available data are mainly retrospective. This review provides an overview of the current knowledge on preoperative nutritional screening and optimization in IBD patients and identifies avenues for future research and clinical practice. Interdisciplinary collaboration among healthcare professionals, including gastroenterologists, surgeons, dietitians, physiotherapists, and psychologists, is crucial for comprehensive preoperative nutritional management in IBD patients. By addressing the interplay between inflammation, malnutrition, and surgical risk, clinicians can strive to enhance surgical care and postoperative outcomes. In conclusion, while recognizing the importance of preoperative nutritional optimization in improving surgical outcomes for IBD patients, challenges persist in standardizing management protocols. Prospective studies are needed to establish such protocols and evaluate the effectiveness of different nutritional strategies.

A real-world longitudinal study implementing digital screening and treatment for distress in inflammatory bowel disease (IBD): The COMPASS-IBD study protocol.

INTRODUCTION: Co-morbid anxiety and depression (distress) in inflammatory bowel disease (IBD) results in poorer outcomes and increased healthcare burden. IBD services require scalable treatment pathways for distress to meet this need. This real-world longitudinal study evaluates the implementation of a new integrated care pathway for distress including: 1) routine mental health screening and 2) therapist-guided, digital CBT tailored to the challenges of living with IBD (compass with adaptations for IBD: COMPASS-IBD) in a UK National Health Service (NHS) large gastroenterology service (~ 5000 patients). METHODS: We describe a mixed-methods, observational, real-world longitudinal study. Routine mental health screening in the IBD service will identify patients with distress (using pre-defined clinical cut-offs), who will be triaged to determine appropriate treatment pathways (including participation in the COMPASS-IBD study). Participants will receive COMPASS-IBD online for ~12 weeks (including 6 × 30-min therapist sessions). Key implementation outcomes will assess reach and adoption of the new pathway using aggregate data on uptake of mental health screening, eligibility, and consent rates for COMPASS-IBD, and number of COMPASS-IBD sessions completed. Interviews with patients and healthcare providers will primarily assess acceptability of the new pathway. Potential effectiveness will be assessed using participant questionnaires at pre-intervention, 12-weeks (post-intervention), and 6-month follow-up. The primary effectiveness outcome will be pre-post changes in distress (PHQ-ADS scores). Quantitative data will be summarised using descriptive statistics and qualitative data analysed using reflexive thematic analysis. CONCLUSION: Study findings will inform treatment pathways for co-morbid distress in IBD, and highlight adaptations required to increase future scalability and effectiveness. TRIAL REGISTRATION NUMBER: NCT05330299 (clinicaltrials.gov).

Iron Regulatory Protein 1 is Required for the Propagation of Inflammation in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD) are complex disorders. Iron accumulates in the inflamed tissue of IBD patients, yet neither a mechanism for the accumulation nor its implication on the course of inflammation are known. We hypothesized that the inflammation modifies iron homeostasis, affects tissue iron distribution and that this in turn perpetuates the inflammation. This study analyzed human biopsies, animal models and cellular systems to decipher the role of iron homeostasis in IBD. We found inflammation-mediated modifications of iron distribution, and iron-decoupled activation of the iron regulatory protein (IRP)1. To understand the role of IRP1 in the course of this inflammation-associated iron pattern, a novel cellular co-culture model was established, that replicated the iron-pattern observed in vivo, and supported involvement of nitric oxide in the activation of IRP1 and the typical iron pattern in inflammation. Importantly, deletion of IRP1 from an IBD mouse model completely abolished both, the misdistribution of iron and intestinal inflammation. These findings suggest that IRP1 plays a central role in the coordination of the inflammatory response in the intestinal mucosa and that it is a viable candidate for therapeutic intervention in IBD.

Age-related patterns of microbial dysbiosis in multiplex inflammatory bowel disease families.

OBJECTIVE: IBD is characterised by dysbiosis, but it remains unclear to what extent dysbiosis develops in unaffected at-risk individuals. To address this, we investigated age-related patterns of faecal and serum markers of dysbiosis in high-risk multiplex IBD families (two or more affected first-degree relatives). DESIGN: Faecal and serum samples were collected from multiplex IBD and control families (95 IBD, 292 unaffected, 51 controls). Findings were validated in independent cohorts of 616 and 1173 subjects including patients with IBD, infants born to mothers with IBD and controls. 16S rRNA gene sequencing and global untargeted metabolomics profiling of faeces and serum were performed. RESULTS: Microbial and metabolomic parameters of dysbiosis progressively decreased from infancy until age 8. This microbial maturation process was slower in infants born to mothers with IBD. After age 15, dysbiosis steadily increased in unaffected relatives throughout adulthood. Dysbiosis was accompanied by marked shifts in the faecal metabolome and, to a lesser extent, the serum metabolome. Faecal and serum metabolomics dysbiosis indices were validated in an independent cohort. Dysbiosis was associated with elevated antimicrobial serologies but not with faecal calprotectin. Dysbiosis metrics differentiated IBD from non-IBD comparably to serologies, with a model combining calprotectin, faecal metabolomics dysbiosis index and serology score demonstrating highest accuracy. CONCLUSION: These findings support that dysbiosis exists as a pre-disease state detectable by faecal and serum biomarkers for IBD risk prediction. Given the expansion of disease-modifying agents and non-invasive imaging, the indices developed here may facilitate earlier diagnoses and improved management in at-risk individuals.

The Contribution of Genetic and Epigenetic Factors: An Emerging Concept in the Assessment and Prognosis of Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) represents heterogeneous and relapsing intestinal conditions with a severe impact on the quality of life of individuals and a continuously increasing prevalence. In recent years, the development of sequencing technology has provided new means of exploring the complex pathogenesis of IBD. An ideal solution is represented by the approach of precision medicine that investigates multiple cellular and molecular interactions, which are tools that perform a holistic, systematic, and impartial analysis of the genomic, transcriptomic, proteomic, metabolomic, and microbiomics sets. Hence, it has led to the orientation of current research towards the identification of new biomarkers that could be successfully used in the management of IBD patients. Multi-omics explores the dimension of variation in the characteristics of these diseases, offering the advantage of understanding the cellular and molecular mechanisms that affect intestinal homeostasis for a much better prediction of disease development and choice of treatment. This review focuses on the progress made in the field of prognostic and predictive biomarkers, highlighting the limitations, challenges, and also the opportunities associated with the application of genomics and epigenomics technologies in clinical practice.

Eosinophilic Esophagitis and Inflammatory Bowel Disease: What Are the Differences?

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are chronic inflammatory disorders of the gastrointestinal tract, with EoE predominantly provoked by food and aeroallergens, whereas IBD is driven by a broader spectrum of immunopathological and environmental triggers. This review presents a comprehensive comparison of the pathophysiological and therapeutic strategies for EoE and IBD. We examine the current understanding of their underlying mechanisms, particularly the interplay between environmental factors and genetic susceptibility. A crucial element in both diseases is the integrity of the epithelial barrier, whose disruption plays a central role in their pathogenesis. The involvement of eosinophils, mast cells, B cells, T cells, dendritic cells, macrophages, and their associated cytokines is examined, highlighting the importance of targeting cytokine signaling pathways to modulate immune-epithelial interactions. We propose that advances in computation tools will uncover the significance of G-protein coupled receptors (GPCRs) in connecting immune and epithelial cells, leading to novel therapies for EoE and IBD.

Ulcerative colitis: the healing power of macrophages.

Ulcerative colitis (UC) is a chronic and debilitating disorder that falls under the broad category of inflammatory bowel disease (IBD). Therefore, affects the colon and rectum, resulting in inflammation and ulcers in the lining of these organs. Over the years, there has been a significant shift in the management of UC. The focus has moved from achieving symptom-free daily living to attaining mucosal healing. Mucosal healing means completely restoring the colon and rectum's lining, significantly reducing the risk of complications and relapse. Macrophages are a crucial component of the immune system that play a vital role in the regeneration and repair of colonic ulcers. These immune cells are responsible for production of a variety of cytokines and growth factors that facilitate tissue repair. Macrophages are responsible for maintaining a balance between inflammation and healing. When this balance is disrupted, it can lead to chronic inflammation and tissue damage, exacerbating UC symptoms. Thus, this review aims to investigate the contribution of macrophages to mucosal repair and remission maintenance in UC patients.

The costs of home monitoring by telemedicine versus standard care for inflammatory bowel diseases - a Danish register-based, five-year follow-up study.

BACKGROUND AND AIMS: There are few studies on the cost-effectiveness of telemedicine for inflammatory bowel diseases (IBD). We assessed the long-term cost-effectiveness of a telemedicine solution (eCare) compared to standard care (sCare), as well as its efficacy according to patient-reported outcomes (PRO). METHODS: Between 2015 and 2020 we conducted a retrospective, register-based study among patients with ulcerative colitis (UC) and Crohn's disease (CD). Direct and indirect healthcare costs over a five-year period were obtained from Danish registers and compared to a control group. Costs were estimated on a yearly basis from one year before, until five years after, inclusion in the trial. Patients were divided into cohorts of those not receiving (cohort 1), and those receiving (cohort 2), biologics. RESULTS: We recruited 574 IBD patients. In cohort 1 (61.5%), average total direct costs and total earnings per patient per year were €14,043 and €307,793 in eCare compared to €16,226 and €252,166 in sCare, respectively. In cohort 2 (38.5%), average total direct costs and total earnings were €73,916 and €215,833 in eCare compared to €41,748 and €203,667 in sCare, respectively. PRO showed increasing quality of life and was higher in cohort 1 than cohort 2. Disease activity among CD patients increased after years 3 and 4 in cohorts 1 and 2, respectively. CONCLUSION: Telemedicine is cost-effective for patients not receiving biologics. However, treatment with biologics is more expensive for patients enrolled in eCare. Careful attention to PRO in eCare improves quality of life and could prolong time to relapse.

A Family of Cyclic Lipopeptides Found in Human Isolates of Bacillus Ameliorates Acute Colitis via Direct Agonism of Toll-Like Receptor 2 in a Murine Model of Inflammatory Bowel Disease.

BACKGROUND: The Bacillus-derived cyclic lipopeptides (surfactin, iturin, and fengycin) form potent Heterogeneous Lipopeptide Micelle (HeLM) complexes. HeLM is a small molecule that has been shown to have immunomodulatory effects. However, how HeLM regulates inflammation is not clear, moreover its application to Inflammatory Bowel Disease (IBD), specifically Ulcerative Colitis (UC), has not been tested before. AIMS: To use a murine model of IBD and determine the effects of HeLM and related molecular mechanisms of action. METHODS: Colitis was induced in mice by administration of 4% Dextran Sodium Sulfate. Three preparations were tested against negative and positive controls: Purified HeLM, the wild-type strain that produces it, and an isogenic mutant that does not produce HeLM. Clinical, biochemical, and histological scoring systems were used to assess the severity of colitis. RT-qPCR and cell cultures were used to determine the levels of molecular signaling. Fecal samples were processed for metagenomic analysis. RESULTS: Purified HeLM, and the wild-type strain, significantly decreased the severity of colitis as determined by the disease activity index (DAI), mouse colitis histology index (MCHI), fecal calprotectin, and colonic length. This effect was not seen in the mutant. HeLM was found to be an agonist to TLR-2, seemingly activating the Toll-Like Receptor 2/IL-10 pathway, with subsequent downregulation of inflammatory cytokines (TNF-α, IL-1ß, and IL-6). At higher concentrations HeLM inhibited lipopolysaccharide ligands from activating TLR-4. The reduction in colitis was not due to microbiome modulation, as had previously been hypothesized. CONCLUSION: Our results indicate that HeLM ameliorates colitis by TLR-2-induced IL-10 production and possibly via the inhibition of lipopolysaccharide.