Idiopathic Inflammatory Bowel Disease Research Articles

Protective effect of soluble dietary fiber from Rosa roxburghii Tratt residue on dextran sulfate sodium-induced ulcerative colitis by regulating serum metabolism and NF-κB pathway in mice.

Ulcerative colitis (UC) refers to an idiopathic chronic inflammatory bowel disease that starts with inflammation of the intestinal mucosa. Dietary fiber plays a crucial role in maintaining the normal architecture of the intestinal mucosa. In this study, the protective effect and potential mechanism of soluble dietary fiber from Rosa roxburghii Tratt residue (SDFR) on dextran sulfate sodium (DSS)-induced UC mice were explored. The results revealed that SDFR could ameliorate body weight loss and pathological injury, improve the structure and crypt destruction in colon in DSS-induced mice. Moreover, the levels of NO, IL-1β, TNF-α, MPO and protein expression of iNOS and COX-2 were decreased after administration of SDFR. Notably, nontargeted metabolomics analysis indicated that there were significant differences in 51 potential metabolites in serum between the DSS and control groups. SDFR intervention could regulate aberrant alterations of these metabolites and mitigate UC via regulating metabolic pathways, including arachidonic acid and glycerophospholipid metabolism. This study provides novel evidence that SDFR could be used as a potential modulator to relieve UC. Also, the results provide a theoretical basis for the utilization of byproducts in Rosa roxburghii Tratt fruit processing. © 2024 Society of Chemical Industry.

Ayurvedic Management of Crohn’s Disease - A Single Case Study

Crohn’s disease is a chronic idiopathic inflammatory bowel disease condition characterized by skip lesions and transmural inflammation that can affect the entire gastrointestinal tract from the mouth to the anus. It is having variable presenting symptoms and may include diarrhoea, abdominal pain, weight loss, nausea, vomiting etc. The diagnosis is typically made with endoscopic and/or radiologic findings. A 16-year-old female patient diagnosed with Crohn’s disease having complaints of frequent loose stools, bleeding per rectum after evacuation of bowel, generalised weakness, reduced appetite and weight loss since more than 6 years approached the outpatient department of Kayachikitsa, SDM Ayurveda hospital, Kuthpady, Udupi, Karnataka, India. Patient was intervened with Vilwadi Gulika, Dadimashtaka Churna, Kutajarishta, Takra Kalpana, Parpati Kalpana, Picha Basti etc. strictly following Laja diet with Takra in 4 courses of admissions with a time gap of 2-3 months. There was marked improvement in the frequency of loose stools and rectal bleeding. Improvement in weight was noted by a gain of 12 kg and generalised weakness was completely relieved. The therapy gained confidence in the patient to stop all the steroid and immunosuppressant medications completely and continue with Ayurvedic medication. Thus, it can be concluded that Ayurvedic interventions are effective in the improvement of symptoms in Crohn’s disease.

Tacrolimus-Associated Terminal Ileitis After Kidney Transplantation, Mimicking Crohn Disease: A Case Report

The onset of gastroduodenal ulcers is a frequent complication after transplantation, whereas cases of intestinal ulcers are sporadic and poorly described in the literature. A patient on immunosuppressive therapy with tacrolimus and mycophenolate mofetil after kidney transplant for immunoglobulin A-related glomerulonephritis developed symptoms compatible with Crohn disease 7 months after the transplant. The patient was hospitalized for abdominal pain, diarrhea, fever, and weight loss. Imaging and a colonoscopy showed signs of idiopathic inflammatory bowel disease (IBD) affecting the terminal ileum. Behcet's disease, post-transplant lymphoma, cytomegalovirus, Epstein-Barr virus, or mycobacteria infection were excluded. Mycophenolate mofetil was suspended, and steroid therapy was increased without clinical improvement. Eleven units of blood were required for severe anemia. A further colonoscopy revealed ulcerations involving the cecal fundus, ileocecal valve, and distal ileum with bowel stenosis and suspected ischemia. The patient, therefore, underwent an emergency laparoscopic ileocolic resection. The histologic examination did not reveal clear signs of IBD, ischemia, or viral infection of the ileum. The findings seemed indicative of iatrogenic damage from immunosuppressive therapy. The postoperative course was regular, and after 12 months, the patient was asymptomatic, on low-dose tacrolimus and prednisone therapy. During immunosuppressive therapy, the onset of isolated ileal ulcers, which can mimic IBD, may be a sporadic complication.

A193 DECIPHERING THE INFLUENCE OF CROHN’S DISEASE-ASSOCIATED GENETIC RISK FACTOR, NOD2 IN INTESTINAL FIBRO-STENOSIS

Abstract Background Intestinal fibrosis (IF) is a common debilitating complication associated with Crohn’s disease (CD), an idiopathic inflammatory bowel disease (IBD). IF results in severe strictures that affect the entire gastrointestinal tract, often requiring surgery due to limited or no effective treatment. In general, IF is a consequence of chronic inflammation, excessive extracellular matrix (ECM) deposition, aberrant cellular functions and tissue remodeling involving the innate and adaptive immune system. At the cellular level, fibrosis has been proposed to involve the crosstalk between epithelial cells, mesenchymal stromal cells and immune cells. However, the cascade of events that establish IF is poorly understood as it comprises a dynamic interplay between host genetics, immunity, gut microbiome and aberrant environment insults. Notably, polymorphisms in nucleotide-binding oligomerization domain-containing protein 2 (NOD2; a bonafide cytosolic innate immune receptor), strong genetic risk factors for CD, also increase the incidence of IF. In this context, how NOD2 polymorphisms govern intestinal fibrostenosis in CD remains to be investigated. Aims To investigate how CD-associated risk gene, NOD2 contributes to intestinal fibrostenotic disease Methods We employed a single-cell RNA sequencing (scRNA-seq) approach to explore the cellular landscape in our CD-mouse model, where we challenged Nod2-deficient mice with a chronic inflammatory insult regime, using dextran sulfate sodium (cDSS) for 3 cycles. Subsequently, changes in inflammatory, metabolic and fibrotic markers in the gut were analyzed by quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC) or western blot analyses. Further, RNA-In-situ hybridization (RNA-ISH) and flow cytometric analyses were performed to validate cell populations contributing to, and the molecular signatures linked with intestinal fibrostenosis. Results We found that Nod2-deficient mice show increased expression of pro-inflammatory cytokines (TNF, IL6) and excessive ECM deposition (fibrosis) in the gut compared to wild-type littermate mice post-cDSS. Curiously, scRNA-seq analysis uncovered altered stromal-immune-cell crosstalk along with the identification of a novel subset of the Dpt+ interstitial stromal population with distinct gene signatures regulated by chronic inflammation. Further, we observed increased senescence (Cdkn2a) mediated trans-differentiation of stroma into fibroblast contributing to IF in Nod2-deficient mice. Conclusions The study outlined will deepen our understanding of cellular and molecular mediators as well as inter and intra-cellular networks that drive IF. This will be transformative in devising therapeutic strategies to prevent IF in progressive CD patients. Funding Agencies CCC, CIHRThe American Association of Immunologist (AAI)

MANAGEMENT OF INFLAMMATORY BOWEL DISEASE IN AYURVEDA PER-SPECTIVE – A CASE STUDY

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease with a relapsing nature. It is a very chal-lenging disease affecting a patient during the most active period of his life, i.e., 20 to 40 years of age. The main features are anorectal bleeding with increased frequency of bowel evacuation, general debility and abnormal structural pathology in the descending colon, particularly the sigmoid colon. Modern medical science has no permanent curative and safe treatment for this disease. Thus, the following article discusses the method of treat-ment of the disease using Ayurvedic treatment by shamana aushadhis (Guloochyadi kashayam, Hinguvachadi gulika, Dadimashtaka choorna, Dhanvantharam gulika etc). Based on the signs and symptoms observed in the patient, a treatment protocol was advised. It can become a new way to achieve effective and safe care treatment and significantly improve a patient’s condition. A patient aged 64 years. The Male complained of pain in the abdomen, very bad-smelling mucous discharge in the morning while defecating, loss of appetite, feeling of swelling in the anal region, and pain in HIP bilaterally. Based on the patient’s condition, prakruti and samprapti ghatak (pathological factors) a treatment protocol was designed with the shamana chikitsa. The combination of various powdered herbs like Guloochyadi kashayam, Hinguvachadi gulika, Dadimashtaka choorna, Dhanvantharam gulika etc were advised to the patients with prop-er dietary instructions and restrictions. The treatment protocol effectively reverses the main symptoms, and it could be extended in future cases by using different combinations of drugs based on other Ayurvedic parameters to obtain even better results. It showed marked improvement in the patient’s condition. According to one’s Pra-kriti and combinations of various potential ingredients, diets and lifestyle recommendations, it worked on overall disease management. The management strategy was efficacious in improving the patients’ main issues. The case was treated with compound ayurvedic medicines over 3 months with remarkable improvement, which is evident. The outcome of this clinical study will reveal further the effect of ayurvedic medicine on IBD.

MR Enterography in Ulcerative Colitis: Beyond Endoscopy.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) that progressively affects mucosa and submuccosa of the colon and rectum in a continual pattern. In comparison, Crohn disease (CD), the other type of IBD, is a chronic transmural inflammatory disorder that can involve any part of the gastrointestinal tract. MR enterography (MRE) has emerged as an important imaging modality for the diagnosis and detection of disease activity and complications in CD, with comparable results to those of endoscopy. But MRE has been underused for assessment of UC in recent years, and clinicians heavily rely on endoscopic findings for management of UC. Despite UC being considered an endoscopically assessable disease, MRE can provide useful information beyond that obtained with endoscopy about mural or extramural abnormalities, inaccessible parts of the colonic lumen, associated extraintestinal diseases, and superimposed pathologic conditions. Moreover, endoscopy might be contraindicated in some clinical settings due to the risk of colonic perforation. In addition to depicting the features of UC activity in different phases, MRE demonstrates findings of disease chronicity that cannot be achieved with endoscopy, particularly in a patient with colitis of unknown cause. The valuable diagnostic role of MRE to exclude undiagnosed CD in patients with UC who have refractory disease or those with postproctocolectomy complications is also emphasized. Radiologists can play a crucial role in the management of UC with MRE by addressing what is beyond endoscopy. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Bioinspired and biomimetic strategies for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease with high morbidity and an increased risk of cancer or death, resulting in a heavy societal medical burden. While current treatment modalities have been successful in achieving long-term remission and reducing the risk of complications, IBD remains incurable. Nanomedicine has the potential to address the high toxic side effects and low efficacy in IBD treatment. However, synthesized nanomedicines typically exhibit some degree of immune rejection, off-target effects, and a poor ability to cross biological barriers, limiting the development of clinical applications. The emergence of bionic materials and bionic technologies has reshaped the landscape in novel pharmaceutical fields. Biomimetic drug-delivery systems can effectively improve biocompatibility and reduce immunogenicity. Some bioinspired strategies can mimic specific components, targets or immune mechanisms in pathological processes to produce targeting effects for precise disease control. This article highlights recent research on bioinspired and biomimetic strategies for the treatment of IBD and discusses the challenges and future directions in the field to advance the treatment of IBD.

The unsuspected source of oxygen in Crohn´s Disease

Crohn disease is a chronic idiopathic inflammatory bowel disease condition characterized by skip lesions and transmural inflammation that can affect the entire gastrointestinal tract from the mouth to the anus. Presenting symptoms are often variable and may include diarrhea, abdominal pain, weight loss, nausea, vomiting, and in certain cases fevers or chills. in some cases, extraintestinal manifestations may develop. The diagnosis is typically made with endoscopic and/or radiologic findings. Disease management is usually with pharmacologic therapy; however, most patients will eventually require surgery for their disease. Crohn disease can affect any part of the gastrointestinal tract. About one-third of patients have small bowel involvement, especially the terminal ileum, another 20% have only colon involvement and about 50% be involved of both the colon and small bowel. So far, there is no cure, and most patients experience bouts of remissions and relapse at unpredictable times. This disease leads to very poor quality of life. Our observation that our body does not take oxygen from the air, but from intracellular water, like plants, implies rethinking the etiopathogenesis of the disease. Crohn's disease, because until now, the interpretation of clinical findings is because we take oxygen from the air, when the purpose of breathing is only to expel the CO2 that is continually formed inside our body.

Beneficial Effect of Faecal Microbiota Transplantation on Mild, Moderate and Severe Dextran Sodium Sulphate-Induced Ulcerative Colitis in a Pseudo Germ-Free Animal Model.

Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.

In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs?

PICO Question In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs or improving the canine inflammatory bowel disease (IBD) activity index (CIBDAI) or the canine chronic enteropathy clinical activity index (CCECAI)?   Clinical bottom line Category of research Treatment. Number and type of study designs reviewed One double-blinded randomised control trial. Strength of evidence Moderate. Outcomes reported The outcome of this study identified that no significant differences in remission rates (> 75% decrease in CIBDAI scores) were observed between the prednisone and budesonide groups. Frequency of adverse effects were also similar between the two groups. Conclusion A single study with moderate power of evidence alongside some significant limitations, particularly population size, cannot be used as the sole provider of an answer to the PICO question. As such, further studies with greater power would be required before a definitive assessment of comparative treatment efficacy can be made.   How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Reclassification of Inflammatory Bowel Disease Type Unclassified by Small Bowel Capsule Endoscopy.

Background and Objectives: Ulcerative colitis (UC) and Crohn's disease (CD) are idiopathic inflammatory bowel diseases (IBDs) without a unique, gold standard diagnostic test. UC and Crohn's colitis are impossible to distinguish in approximately 10% of cases. The term IBD type unclassified (IBD-U) is recommended for cases of chronic colitis showing overlapping endoscopic, radiological, and biopsy histological features between UC and CD, while indetermined colitis is reserved for colectomy specimens. Our aim was to assess the role of small-bowel capsule endoscopy (SBCE) in the diagnostic work-up of IBD-U. Materials and Methods: We retrospectively studied the cases of IBD-U explored by SBCE in a tertiary referral gastroenterology center. Patients were investigated using SBCE after contraindications were excluded. Diagnostic criteria for small bowel CD consisted in more than three ulcerations, irregular ulcers, or stenosis, and the Lewis score was used for the quantification of inflammation. The immediate impact of reclassification and outcome data was recorded over a follow-up period of more than one year. Results: Twenty-eight patients with IBD-U were examined using SBCE. Nine patients had small bowel lesions that met the diagnostic criteria for CD, resulting in a reclassification rate of 32.1%. In five of these cases, the treatment was subsequently changed. In the remaining nineteen examinations, no significant findings were observed. There were no complications associated with SBCE. Median follow-up time was 32.5 months (range 12-60). During follow-up, twelve patients were classified as having UC, and seven remained as having an unclassified type; one case of colectomy, for medically refractory UC, was recorded. Conclusions: SBCE is a useful safe tool in the work-up of IBD-U, allowing reclassification in about one third of cases, with subsequent treatment modifications. SBCE may provide a definite diagnosis, enhance the comprehension of the disease's progression, and optimize the short- and long-term management strategy.

S889 The Utility of ChatGPT in the Reporting of Idiopathic Inflammatory Bowel Disease

S889 The Utility of ChatGPT in the Reporting of Idiopathic Inflammatory Bowel Disease

3D Printed Personalized Colon-targeted Tablets: A Novel Approach in Ulcerative Colitis Management.

Ulcerative colitis (UC) and Crohn's disease (CD) are two types of idiopathic inflammatory bowel disease (IBD) that are increasing in frequency and incidence worldwide, particularly in highly industrialized countries. Conventional tablets struggle to effectively deliver anti-inflammatory drugs since the inflammation is localized in different areas of the colon in each patient. The goal of 3D printing technology in pharmaceutics is to create personalized drug delivery systems (DDS) that are tailored to each individual's specific needs. This review provides an overview of existing 3D printing processes, with a focus on extrusion-based technologies, which have received the most attention. Personalized pharmaceutical products offer numerous benefits to patients worldwide, and 3D printing technology is becoming more affordable every day. Custom manufacturing of 3D printed tablets provides innovative ideas for developing a tailored colon DDS. In the future, 3D printing could be used to manufacture personalized tablets for UC patients based on the location of inflammation in the colon, resulting in improved therapeutic outcomes and a better quality of life.

Genistein and/or sulfasalazine ameliorate acetic acid-induced ulcerative colitis in rats via modulating INF-γ/JAK1/STAT1/IRF-1, TLR-4/NF-κB/IL-6, and JAK2/STAT3/COX-2 crosstalk

Ulcerative Colitis (UC) is a chronic idiopathic inflammatory bowel disease in which the colon’s lining becomes inflamed. Exploring herbal remedies that can recover mucosal damage is becoming popular in UC. The study aims to investigate the probable colo-protective effect of a natural isoflavone, genistein (GEN), and/or a drug, sulfasalazine (SZ), against acetic acid (AA)-induced UC in rats, in addition to exploring the possible underlying mechanisms. UC was induced by the intrarectal installation of 1–2 ml of 5% diluted AA for 24 h. Ulcerated rats were allocated into the disease group and three treated groups, with SZ (100 mg/kg), GEN (100 mg/kg), and their combination for 14 days, besides the control groups. The anti-colitic efficacy of GEN and/or SZ was evidenced by hindering the AA-induced weight loss, colon edema, and macroscopic scores, besides reduced disease activity index and colon weight/length ratio. Furthermore, treatments attenuated the colon histopathological injury scores, increased the number of goblet cells, and lessened fibrosis. Both treatments reduced the up-regulation of INF-γ/JAK1/STAT1 and INF-γ /TLR-4/ NF-κB signaling pathways and modulated the IRF-1/iNOS/NO and IL-6/JAK2/STAT3/COX-2 pathways and consequently, reduced the levels of TNF-α and IL-1β. Moreover, both treatments diminished oxidative stress, which appeared by reducing the MPO level and elevating the SOD activity, and hindered apoptosis; proved by the decreased immunohistochemical expression of caspase-3. The current findings offer novel insights into the protective effects of GEN and suggest a superior benefit of combining GEN with SZ, over either drug alone, in the UC management.

Meningococcal ACWY conjugate vaccine immunogenicity and safety in adolescents with juvenile idiopathic arthritis and inflammatory bowel disease: A prospective observational cohort study.

Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs). We performed a prospective observational cohort study in JIA and IBD patients (14-18years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24months postvaccination and compared with data from HCs at baseline and 12months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12months postvaccination. We included 226 JIA and IBD patients (66% and 34% respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p<0·01) in patients compared to HCs at 12months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p<0·01). The proportion protected (SBA≥8) for MenW was reduced in anti-TNF users (76% versus 92% in non-anti-TNF and 100% in HCs, p<0.01). The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered.

Comparison of PUCAI Score in Mesalazine-Treated Children with Ulcerative Colitis

Background: Ulcerative colitis is a chronic idiopathic inflammatory bowel disease (IBD) characterized by intestinal inflammation confined to the superficial mucosal layer. Mesalazine, a 5-aminosalicylic acid (5-aminosalicylic, or 5-ASA) compound, is most often used as first-line therapy for mild to moderate ulcerative colitis. The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a non-invasive multi-item measure that has been shown to be valid, reliable, and responsive to short-term changes in several clinical trials and cohort studies. Therefore, this study aims to compare the PUCAI scores in children with ulcerative colitis who received mesalazine therapy to those who did not. Methods: We performed a retrospective database analysis of 12 patients, who were diagnosed with ulcerative colitis at Dr. Kariadi General Hospital, Semarang, Indonesia in a span of 1 year. We included all cases of pediatric patients with ulcerative colitis, then we divided them into 2 groups, the group receiving mesalazine therapy and the group who did not. We monitored the development of PUCAI scores before and after treatment. Results: The number of samples in this study was 12 samples. All sample data were taken based on data from pediatric gastroenterohepatology patients diagnosed with colitis ulcerative based on pathology anatomy results, who were treated in the pediatric ward of RSUP Dr. Kariadi Semarang. From the result of the paired t-test, there was a significant decrease in PUCAI score in patients who received Mesalazine, (p = 0.007), while those who did not receive mesalazine, did not show any significant decrease in PUCAI score. Conclusion: Ulcerative colitis (UC) is a chronic relapsing inflammatory condition. UC is often treated with mesalazine as the first-line treatment. The use of the PUCAI score is an appropriate tool to determine the progression of this disease. Based on the data obtained, the administration of mesalazine therapy in children with ulcerative colitis can improve PUCAI scores compared to children who do not receive mesalazine therapy.

Serum proteome of dogs with chronic enteropathy.

Chronic enteropathy (CE) is common in dogs and can occur with multiple etiologies including food-responsive enteropathy (FRE) and idiopathic inflammatory bowel disease (IBD). To study the protein profile and pathway differences among dogs with FRE, IBD, and healthy controls using serum proteome analysis. Nine CE dogs with signs of gastrointestinal disease and histologically confirmed chronic inflammatory enteropathy and 16 healthy controls. A cross-sectional study with cases recruited from 2 veterinary hospitals between May 2019 and November 2020 was performed. Serum samples were analyzed using mass spectrometry-based proteomic techniques. Proteomic profiles showed marked variation in relative protein abundances. Forty-five proteins were significantly (P ≤ .01) differentially expressed among the dogs with CE and controls with ≥2-fold change in abundance. The fold change of dogs with IBD normalized to controls was more pronounced for the majority of proteins than that seen in the dogs with FRE normalized to control dogs. Proteins involving reactive oxygen species, cytokine activation, acute phase response signaling, and lipid metabolism were altered in dogs with CE. Cytokine alterations, acute phase response signaling, and lipid metabolism are likely involved in pathogenesis of CE. Although there are insufficient current data to justify the use of proteomic biomarkers for assessment of CE in dogs, our study identifies potential candidates.

Diverse but desolate landscape of gut microbial azoreductases: A rationale for idiopathic IBD drug response

ABSTRACT Prodrugs reliant on microbial activation are widely used but exhibit a range of efficacies that remain poorly understood. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA), which is packaged in a variety of azo-linked prodrugs provided to most Ulcerative Colitis (UC) patients, shows confounding inter-individual variabilities in response. Such prodrugs must be activated by azo-bond reduction to form 5-ASA, a process that has been attributed to both enzymatic and non-enzymatic catalysis. Gut microbial azoreductases (AzoRs) are the first catalysts shown to activate azo-linked drugs and to metabolize toxic azo-chemicals. Here, we chart the scope of the structural and functional diversity of AzoRs in health and in patients with the inflammatory bowel diseases (IBDs) UC and Crohn’s Disease (CD). Using structural metagenomics, we define the landscape of gut microbial AzoRs in 413 healthy donor and 1059 IBD patient fecal samples. Firmicutes encode a significantly higher number of unique AzoRs compared to other phyla. However, structural and biochemical analyses of distinct AzoRs from the human microbiome reveal significant differences between prevalent orthologs in the processing of toxic azo-dyes, and their generally poor activation of IBD prodrugs. Furthermore, while individuals with IBD show higher abundances of AzoR-encoding gut microbial taxa than healthy controls, the overall abundance of AzoR-encoding microbes is markedly low in both disease and health. Together, these results establish that gut microbial AzoRs are functionally diverse but sparse in both health and disease, factors that may contribute to non-optimal processing of azo-linked prodrugs and idiopathic IBD drug responses.

Engineered procyanidin-Fe nanoparticle alleviates intestinal inflammation through scavenging ROS and altering gut microbiome in colitis mice.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease characterized by inflammation, intestinal barrier injury, and imbalance of gut microbiota. Excess accumulation of reactive oxygen species (ROS) is closely correlated with the development and reoccurrence of IBD. Previous researches demonstrate that procyanidin, as a natural antioxidant, exhibits strong ability of eliminating ROS, thus showing good therapeutic effects in the inflammation-related diseases. Non-etheless, its poor stability and solubility always limits the therapeutic outcomes. Here, we typically designed an antioxidant coordination polymer nanoparticle using the engineering of procyanidin (Pc) and free iron (Fe), named Pc-Fe nanozyme, for effectively scavenging ROS and further inhibiting inflammation while altering the gut microbiome for the treatment of colitis. Furthermore, in vitro experiments uncover that Pc-Fe nanoparticles exert strong multi biomimic activities, including peroxidase, and glutathione peroxidase, for the scavenging of ROS and protecting cells from oxidative injury. In addition, the colon accumulation of Pc-Fe nanozyme effectively protects the intestinal mucosa from oxidative damage while significantly downregulates pro-inflammatory factors, repairs the intestinal barriers and alternates gut microbiome after orally administrated in sodium dextran sulfate (DSS) induced colitis mice. The results collectively illustrate that the multienzyme mimicking Pc-Fe nanozyme owns high potential for treating IBD through scavenging ROS, inhibiting inflammation, repairing gut barriers and alternating gut microbiome, which further promising its clinical translation on IBD treatment and other ROS induced intestinal diseases.

Vaccination coverage in children with juvenile idiopathic arthritis, inflammatory bowel diseases, and healthy peers: Cross-sectional electronic survey data.

Patients with immune-mediated diseases, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are at increased risk of developing infections, due to disease-related immune dysfunction and applying of immunosuppressive drugs. To evaluate vaccine coverage in patients with IBD and JIA, and compare it with healthy children. In the cross-sectional study we included the data from a questionnaire survey of 190 Legal representatives of children with JIA (n = 81), IBD (n = 51), and healthy children (HC, n = 58). An electronic online questionnaire was created for the survey. There were female predominance in JIA patients and younger onset age. Parents of JIA had higher education levels. Employment level and family status were similar in the three studied groups. Patients with JIA and IBD had lower vaccine coverage, without parental rejection of vaccinations in IBD, compare to JIA and healthy controls. The main reason for incomplete vaccination was medical conditions in IBD and JIA. IBD patients had a lower rate of normal vaccine-associated reactions compared to JIA and HC. The encouraging role of physicians for vaccinations was the lowest in JIA patients. IBD patients had more possibilities to check antibodies before immune-suppressive therapy and had more supplementary vaccinations compared to JIA and HC. JIA and IBD patients had lower vaccine coverage compared to HC. Physicians' encouragement of vaccination and the impossibility of discus about future vaccinations and their outcomes seemed the main factors for patients with immune-mediated diseases, influencing vaccine coverage. Further investigations are required to understand the reasons for incomplete vaccinations and improve vaccine coverage in both groups, especially in rheumatic disease patients. The approaches that stimulate vaccination in healthy children are not always optimal in children with immune-mediated diseases. It is necessary to provide personalized vaccine-encouraging strategies for parents of chronically ill children with the following validation of these technics.