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Probiotics and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterised by a chronic dysregulation of the inflammatory response in the gastrointestinal tract. While the pathogenesis is unclear, studies have demonstrated that the gastrointestinal tracts of patients with IBD are populated with increased levels of adherent and pathogenic bacteria. This evidence, combined with growing data accumulated from genetic studies as well as animal models of IBD, indicates that an aberrant response to altered enteric flora plays a significant role in the disease process. Current therapies for IBD have been directed towards the development of anti-inflammatory agents and immunomodulators to attenuate the inflammatory response in the gastrointestinal tract. Antibiotics are also partially effective in the treatment of IBD, presumably by altering the bowel flora. However, it is clear from clinical trials that immunomodulators and antibiotics are not effective in a large proportion of patients with IBD and other therapeutic alternatives need to be pursued. Probiotics are microbial supplements capable of recolonising the bowel with non-pathogenic strains of bacteria or yeast. Probiotics have long been shown to be beneficial in both infectious and non-infectious digestive disorders. Growing evidence indicates that probiotics may be effective in the treatment of specific clinical IBD conditions. This article addresses the current evidence for the role of enteric flora in the pathogenesis of IBD and the clinical evidence supporting the use of probiotics in specific clinical IBD conditions.

Animals↗

Evaluation of assays for perinuclear antineutrophilic cytoplasmic antibodies and antibodies to Saccharomyces cerevisiae in dogs with inflammatory bowel disease.

OBJECTIVE: To evaluate the use of immunofluorescence asssays for perinuclear antineutrophilic cytoplasmic antibodies (pANCAs) and antibodies to Saccharomyces cerevisiae (ASCAs) in dogs with inflammatory bowel disease (IBD) and assess the clinical value of these serologic markers of the disease. ANIMALS: 39 dogs with IBD, 18 dogs with acute diarrhea, 19 dogs with chronic non-IBD-associated diarrhea, 26 healthy dogs of various breeds and age, and 22 healthy young working dogs. PROCEDURE: Sera obtained from the dogs in each group were added to canine granulocyte- and Saccharomyces cerevisiae-mounted slides for detection of pANCAs and ASCAs via immunofluorescence techniques. Sensitivity and specificity (with 95% confidence intervals [CIs]) were calculated for the group of dogs with IBD versus each of the 2 groups of healthy dogs, the group of dogs with acute diarrhea, and the group of dogs with chronic non-IBD-associated diarrhea. RESULTS: Among the 39 dogs with IBD, 20 yielded positive results via the pANCA assay (sensitivity, 0.51 [95% CI, 0.35 to 0.67]) and 17 yielded positive results via the ASCA assay (sensitivity, 0.44 [95% CI, 0.22 to 0.69]). The specificity of the pANCA assay in the 4 groups of non-IBD-affected dogs ranged from 0.83 (95% CI, 0.85 to 0.96) to 0.95 (95% CI, 0.72 to 1.00). CONCLUSIONS AND CLINICAL RELEVANCE: Immunofluorescence assays for pANCA and ASCA appear to be useful for the detection of IBD in dogs. The pANCA immunofluorescence assay had high specificity for canine IBD, and pANCAs appear to be accurate markers of intestinal inflammation.

Animals↗

The expression and regulation of class II antigens in normal and inflammatory bowel disease peripheral blood monocytes and intestinal epithelium.

Elevated constitutive expression of major histocompatibility (MHC) class II antigens occurs in the enterocytes of patients with IBD. It has been suggested that this aberrant expression of class II molecules may play a role in the pathogenesis of IBD. We examined two possible reasons for such a finding. 1) Heightened sensitivity of IBD enterocytes to endogenous gamma interferon (gamma IFN) and 2) enhanced endogenous secretion of gamma interferon by intestinal cells in close proximity to the enterocytes (lamina propria lymphocytes). Constitutive and gamma interferon stimulated HLA-DR and DP density on intestinal epithelial cells (IEC) and peripheral blood monocytes (PBM) from UC patients (IEC n = 13; PBM n = 20), CD patients (IEC n = 14; PBM n = 18) and non-IBD controls (IEC n = 12; PBM n = 20) were measured via flow cytometry (mean channel fluorescence). gamma IFN production by PHA stimulated and unstimulated lamina propria lymphocyte (LPL) cultures of UC patients (n = 11) CD patients (n = 8) and non-IBD controls (n = 11) was measured using a vesicular stomatitis virus/WISH cell bioassay. We found significantly greater gamma IFN secretion by IBD-derived PHA stimulated LPL than from non-IBD stimulated controls (CD = 39.4 +/- 12.4u; UC41.5 +/- 6.8u; NL = 22.4 +/- 8.3u, p less than 0.05) while gamma IFN induced HLA-DR and DP upregulation was no greater in IBD-derived IEC and PBM than in non-IBD controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗

Simultaneous application of live turkey herpesvirus and infectious bursal disease vaccines against Marek's disease and infectious bursal disease.

The efficacy of cell-associated (CA) and cell-free (CF) infectious bursal disease (IBD) vaccines in maternal antibody (MAb)-bearing broiler chickens was compared. Compatibility and potency of a mixed vaccine combining live CA turkey herpesvirus (HVT) and CA IBD vaccine viruses were also tested against gross lesions induced by Marek's disease (MD) or IBD in specific-pathogen-free chickens. Both CA and CF IBD vaccines provided significant protection against gross bursal lesions of IBD in the presence of MAb. Although chickens receiving the CA vaccine showed a slightly higher (60 to 86.7%) protective index (PX) than CF vaccine recipients (40 to 66.7%), there was no statistical difference in their PX between comparable CA and CF IBD vaccines. The HVT and IBD virus (IBDV) were compatible when they were combined as a live bivalent mixed HVT-IBDV vaccine. Based on the incidence of gross lesions induced by challenge exposure to MD or IBD, potency of the mixed vaccine was similar to that of the monovalent HVT or IBD vaccine. Antagonism did not occur between the two component vaccines when they were applied simultaneously.

Animals↗

IL1B-centered immune dysregulation involving IL7R, CCR7, ITGB2 and IRF1 across insomnia and inflammatory bowel disease.

BACKGROUND: Insomnia is a prevalent sleep disorder that strongly affects one's quality of life and physical well-being. Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestines, and a majority of IBD patients suffer from comorbid insomnia. However, the shared molecular features linking insomnia and IBD remain poorly characterized. METHODS: Common differentially expressed genes (DEGs) were identified in datasets of insomnia (GSE208668) and IBD (GSE179285) using the Limma package. Functional enrichment was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Protein-protein interaction (PPI) network construction and hub gene identification was subsequently performed. Furthermore, we validated the reliability of the hub genes using qRT-PCR and Enzyme-linked immunosorbent assay (ELISA). In addition, we constructed a TF-miRNA regulatory network of hub genes and assessed the abundance of immune cell infiltration in insomnia and IBD using CIBERSORT, EPIC, and xCell algorithms. Finally, we utilized the DsigDB to predict potential therapeutic candidates. RESULTS: The analysis revealed 75 upregulated and 32 downregulated common DEGs. Functional enrichment analysis revealed the inflammatory response and immune activation as pivotal drivers underlying the pathogenesis of both insomnia and IBD. Five hub DEGs, namely, IL1B, IL7R, CCR7, ITGB2, and IRF1, were subsequently screened and validated. The TF-miRNA-mRNA regulatory network consisted of 5 TFs, 14 miRNA nodes and 5 core mRNA nodes. Immune cell infiltration analysis revealed several patterns shared between insomnia and IBD. Additionally, 10 potential therapeutic drugs for insomnia and IBD were proposed. CONCLUSION: Integrative coexpression network analysis reveals convergent dysregulation of an IL1B-centered immune module (comprising IL7R, CCR7, ITGB2, and IRF1) across insomnia and IBD, a shared immune disturbance and candidate targets for simultaneous intervention upon further mechanistic validation.

Humans↗

Epidemiology of inflammatory bowel disease in Spain. A systematic review.

BACKGROUND AND OBJECTIVES: Incidence and prevalence of Inflammatory Bowel Disease (IBD) differ considerably depending on the geographical region studied. In Spain, both Ulcerative Colitis (UC) and Crohn's Disease (CD) seem to have experienced an important change in terms of incidence during the past decades. Our aim was to systematically review the experience in Spain regarding the epidemiology of IBD, in particular its incidence, its geographical differences and its evolution over time. METHODS: A bibliographical search till January 2000 was conducted in Internet using the PubMed search motor and the following descriptors or key words: "Crohn's disease", "Ulcerative colitis", "Inflammatory bowel disease", "Spain" and "Spanish". Only publications providing data on IBD incidence among Spanish patients were included. References from articles that fulfilled the selection criteria were also reviewed. The endpoints considered in the review were IBD incidence rate, its geographical differences, and its evolution over time. RESULTS: UC incidence reported by different studies performed in Spain ranges from 0.6 to 8 cases/10(5)/year, with a mean value of 3.8. CD incidence rates in Spain ranges from 0.4 to 5.5 cases/105/year, with a mean value of 1.9. Some studies have shown differences in IBD incidence between regions in our country. Many studies have reported an increase in IBD incidence in Spain over time, although such increase is more evident in the case of CD. CONCLUSIONS: UC incidence in Spain ranges from 0.6 to 8 cases/105/year, with a mean value of 3.8. CD figures range from 0.4 to 5.5 cases/105/year, with an average rate of 1.9. IBD incidence seems to be relatively different depending on the geographical region studied. Finally, several authors have demonstrated an increase in IBD incidence in Spain over time, although such increase seems to be more evident in the case of CD. Consequently, IBD in Spain is no longer considered a rare disease, but a relatively frequent one.

Humans↗

Evaluation of efficacy of enamel matrix derivative in the treatment of intrabony defects: a 24-month multicenter study.

The aim of this prospective multicenter controlled clinical study was to evaluate the efficacy of Emdogain (Biora), an enamel matrix derivative (EMD), when combined with surgical treatment of periodontal angular defects, as compared to surgery alone, for up to 24 months of follow-up. The study was performed at six Italian universities and 11 private practices. Patients with one-, two-, or three-wall angular defects were enrolled if intrabony defect depth (IBD) was 4 mm or more and probing pocket depth (PPD) was at least 6 mm. They were randomly allocated to either test or control groups. The test group was treated by the simplified papilla preservation (SPP) flap plus Emdogain after root conditioning with ethylenediaminetetraacetic acid. The control group was treated by SPP alone. Plaque Index, Gingival Index, PPD, and periodontal attachment level (PAL) at surgical sites were assessed at the presurgical examination (baseline). IBD was measured intraoperatively after debridement. IBD was also evaluated with a computer-aided technique, from periapical radiographs. Plaque Index, Gingival Index, PPD, PAL, and IBD were assessed at 12 and 24 months postsurgery. Data were further divided in two subgroups according to baseline IBD (6 mm or less and more than 6 mm). The differences between each follow-up and baseline, and between groups at each follow-up, for the above parameters were evaluated by standard statistical methods. One hundred fifty-three patients were recruited, accounting for 195 intrabony defects: 83 patients (108 defects) and 70 patients (87 defects) were allocated to the test and control groups, respectively. All parameters were improved at both 12 and 24 months, compared to baseline in both groups. In the test group, IBD, PPD, and PAL at 12 months were significantly better than these parameters in the control group. The test subgroup with IBD of more than 6 mm at baseline displayed a better outcome when compared to the 6 mm or less IBD subgroup. No significant adverse events related to the use of Emdogain were reported. The use of EMD as an adjunct to periodontal surgery in the treatment of angular defects significantly enhanced the rate and degree of periodontal regeneration. The control group also displayed significant tissue regeneration, but at a slower rate compared to the Emdogain group. The surgical procedure itself, with its goal of maximum preservation of the regenerative potential of periodontal tissues, proved to be effective in the treatment of periodontal angular defects. Pockets with IBD greater than 6 mm showed major improvement when treated with Emdogain.

Adult↗

[Intestinal complications and extraintestinal manifestations in children with inflammatory bowel disease].

UNLABELLED: In 15-20% of patients with inflammatory bowel disease (IBD) the disease starts during children period. The often observed consequences of the early start of the IBD are growth delay, undernutrition and pubertal delay. These problems are specific for pediatric population, in comparison with adults IBD patients. AIM: The assessment of the frequency and character of intestinal complications (IC) and extraintestinal manifestations (ElM) in children with IBD (ulcerative colitis - UC and Crohn disease - CD). MATERIAL AND METHODS: The frequency and character of IC and EIM in 184 children with IBD: 158 with UC (76 boys and 82 girls) aged from 2 to 18 years, and 26 with CD (14 boys and 12 girls) aged from 2 to 18 years were assessed. The frequency of IC and EIM in both groups of children Was compared statistically (chi-square test). RESULTS: Massive intestinal haemorrhage was observed in 11 children with UC. Perianal changes were present in 5 children with CD (significantly more often than in children with UC, p<0.05). External intestinal fistulae (p<0.0005), abdominal abscess, intestinal perforation and ileus (p<0.05) were characteristic complications of CD in comparison with UC. 50% of children with UC and 80% those with CD (statistically significant, p<0.005) had experienced, at least one ElM. Secondary anemia and growth delay were observed in 40,5% and 27,8% of children with UC and in 70% (p<0.05) and 80% (p<0.0001) of children with CD respectively. In children with IBD we observed also autoimmunologic hepatitis, primary sclerosing cholangitis, nephrolithiasis, pulmonary interstitial fibrosis, pancreatitis, neurological changes, skin manifestations and arthritis. Osteopenia was observed in 41% of children with CD and in 25% of children with UC. a CONCLUSIONS: A high prevalence of intestinal complications ane extraintestinal manifestations of IBD in pediatric population is observed. In children with IBD extraintestinal manifestations often occur before the onset of gastrointestinal symptoms. The presence of intestinal complications and extraintestinal manifestations in children with IBD should be considered during modification of therapeutic strategies.

Abdominal Abscess↗

[The significance of IL-13 gene +2044G/A mutation in patients with inflammatory bowel disease].

BACKGROUND: Inflammatory bowel disease (IBD) is caused by a combination of genetic, immunological and environmental factors. Despite recent advances in the study of IBD pathogenesis, including the discovery of the NOD2/CARD15 mutation in 40% of Crohn's Disease (CD) patients, in most IBD patients no known mutations have yet been discovered. The interleukin (IL)-13 gene is located near the IBD5 locus on chromosome 5q31, known to be in linkage disequilibrium with CD. IL-13 has a role in the pathogenesis of several chronic inflammatory diseases including IBD. The +2044G/A mutation, which encodes an IL-13 protein with glutamine instead of arginine, has been associated with various inflammatory conditions. However, its role in IBD has not been defined. AIM: This is a study of the role of the IL-13 gene +2044G/A mutation in the susceptibility to and phenotype of IBD. METHODS: Two hundred and eighty-five patients with CD and 111 cases of ulcerative colitis (UC) were enrolled in the study. Mutation frequency was determined using restriction fragment length polymorphism study in IBD patients and 178 healthy ethnically matched controls. The mutated allele frequency was determined in various clinical sub-groups of IBD patients. Statistical significance of the differences in allele frequency in CD and UC patients and healthy controls was determined. RESULTS: The +2044G/A allele frequency was similar in CD, UC and healthy controls (23.3%, 19.4%, 19.6%, respectively, p = 0.294). There was no significant association of +2044G/A mutation carriage with specific phenotypes of CD and UC. CONCLUSION: The IL-13 gene +2044G/A mutation has no significant role in susceptibility to and phenotype of IBD.

Colitis, Ulcerative↗

Alteration of natural killer cell subsets (two color analysis) and their activity in peripheral blood in inflammatory bowel disease.

The natural killer (NK) activity and NK cell subsets in peripheral blood were evaluated in patients with inflammatory bowel disease (IBD), by using 51Cr release cytotoxicity assay and two color flowcytometry analysis. The peripheral blood NK activity was significantly lower in IBD than that in normal controls. This decrease of the NK activity was independent on the disease activity of IBD but dependent on the steroid medication. The total population of NK cells (Leu 7+ or 11c+ cells) did not change in IBD as compared with those of normal controls. However, the proportions of Leu7+11c- cells and Leu7-11c+ cells in IBD were higher and lower, respectively as compared with those of normal controls. These findings suggest that the maturation step of NK cell lineages might be impaired in IBD. The decrease of NK activity in IBD was supported by the change in the proportion of NK cell subsets described above. It was thought that such a change in NK cell subsets might be a specific finding in IBD patients, because it was not observed in patients with non-IBD colitis.

Adult↗

Disease-related worries and concerns: a study on out-patients with inflammatory bowel disease.

OBJECTIVE: To investigate the relationship between inflammatory bowel disease (IBD) patients' disease-related worries and concerns and their disease-related data, sociodemographic variables and perceived information level with respect to IBD. STUDY DESIGN: Prospective evaluation of disease-related concerns. SETTING: Out-patient IBD clinic of a university hospital. STUDY POPULATION: The study included 105 patients with IBD (72 with Crohn's disease and 33 with ulcerative colitis). MEASUREMENTS: Worries and concerns were measured using the standardized 25-item rating form of IBD patient concerns; actual disease activity was assessed by physicians using the Crohn's disease and clinical activity indices. Sociodemographic and other disease-related data were collected using a structured questionnaire. Patients' perceived information level was measured using a visual analogue scale. RESULTS: The issues of greatest concern to our patients were, in descending order of importance, having an ostomy bag (mean score +/- SD 63.6 +/- 38), the effects of medication (53.1 +/- 34), having surgery (51.6 +/- 36), the uncertain nature of the disease (46.5 +/- 32) and energy level (41.5 +/- 34). Patients with ulcerative colitis scored higher with respect to concern about loss of bowel control (P < 0.03). Disease-related worries and concerns correlated poorly with disease-related data (actual disease activity, severity of the course of IBD, diagnosis, disease duration or location, medication) but showed a significant negative correlation with patients' perceived information level about IBD (t = 0.2, P < 0.004). Lower information-level scores were associated with greater concerns. CONCLUSION: We conclude that the patients' information level about IBD and disease-related concerns have to be considered in clinical practice. Better information about IBD and psychosomatic counselling for patients who show high levels of concern may improve their quality of life and clinical care.

Adolescent↗

A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease.

OBJECTIVES: We describe 14 patients who developed inflammatory bowel disease (IBD) after transplantation despite immunosuppression. METHODS: Using an electronic medical archival retrieval system, records of 6800 liver and kidney transplant patients were searched for evidence of IBD. The pathology was reviewed, and infectious etiologies were excluded. RESULTS: Fourteen patients developed IBD after transplantation. Twelve patients had undergone liver transplantation, and two kidney transplantation. Four had transplantation for autoimmune hepatitis; four for non-A, non-B, non-C hepatitis; two for primary sclerosing cholangitis; one for giant cell hepatitis; one for biliary atresia; one for polycystic kidney disease; and one for obstructive uropathy. Mean age at development of IBD was 38 yr. Mean time to development of IBD after transplantation was 4 yr. Endoscopically there were two cases limited to the left side, eight of pancolitis, of which one had terminal ileal disease, and four of patchy colitis. Histology was consistent with ulcerative colitis in nine patients and Crohn's disease in five. Patients with ulcerative colitis either responded and remained in remission on maintenance therapy (seven of nine) or were refractory and required a colectomy (two of nine). Patients with Crohn's disease continued to have flares despite treatment (five of five). CONCLUSION: 1) New onset IBD can develop after solid organ transplantation, despite use of immunosuppressive therapy. 2) A full spectrum of IBD can be seen after transplantation. 3) Study of these patients could shed light on why immunosuppression is not uniformly effective for IBD and provide clues to the inflammatory determinants of IBD.

Adolescent↗

Increased titer of anticardiolipin antibodies represents the risk for the development of ischemic brain disease in persons below 50.

The aim of this paper was to investigate the frequency of increased ACLA titer in patients with ischemic brain disease (IBD) and to define their clinical profile. The group consisted of 162 IBD patients of both sexes, aged 39-81 years, with 50 healthy volunteers and 23 patients with other neurological diseases as control. Increased ACLA titer (above 0.9 GPL U/l IgG and 0.5 MPL U/l IgM) was registered in 17.9% IBD patients, and more frequently in patients with transitory ischemic attacks (TIA)-32.6%; slightly increased titer predominated (0.9-20 GPL U/l IgG and 0.5-15 MPL U/l IgM) in 69% IBD patients, while moderately increased (20-80 GPL U/l and 15-50 MPL U/l IgM) was present in 21% IBD patients, while highly increased titer (above 80 GPL U/l IgG and above 50 MPL U/l IgM) was present in 10.3%; IgG class was most frequently increased (9.2%), than IgM-5%, while increase of both classes was present in 3.7%. All patients with increased ACLA titer were below 50 years of age, had history of previous IBD attacks, more often TIA, irregularity of at least one coagulation test and fewer risk factors for IBD. Hence, increased ACLA titer was present in IBD patients of both sexes, below 50 years of age with previous history of IBD attacks and fewer atherosclerosis risk factors.

Adult↗

The importance of the family context in inflammatory bowel disease.

BACKGROUND: This study examines psychological correlates of inflammatory bowel disease (IBD) to answer these questions: What is the association between individual and family stress levels and the patient's coping ability and severity of illness? How does the level of family functioning correlate with individual coping and illness severity? To what extent are patient and family beliefs about IBD related to symptomatology? METHODS: Seventeen patients and 44 of their family members were studied intensively in an exploration of the psychological response to IBD. They completed a comprehensive battery of self-report questionnaires assessing stressful life events, coping related to the illness, and beliefs regarding IBD. Ratings of family functioning were made from videotaped family discussions about IBD. Treating physicians made independent ratings of past and current disease severity. RESULTS: Surprisingly, recent disease activity was negatively correlated with family stress level (r = -0.794), but was not associated with patient stress level. However, impaired coping with IBD by affected individuals was directly correlated with both individual (r = 0.595) and family-wide (r = 0.724) reported stress levels. Disease severity was also found to be responsive to family communication style (r = 0.431) and to level of family agreement (r = 0.531) regarding the etiology and management of IBD. CONCLUSIONS: These findings suggest that individual stress affects coping with IBD, whereas family-wide stress, communication style, and agreement about disease etiology and management are related to disease activity. The interrelationship of family and patient as well as individual coping with IBD should be evaluated in future studies.

Adaptation, Psychological↗

Hidradenitis Suppurativa and Smoking, Obesity, Psoriasis, Inflammatory Bowel Disease, and Systemic Sclerosis: Results From A 2-Sample Mendelian Randomization Study.

IMPORTANCE: Smoking and obesity are associated with risk of hidradenitis suppurativa, and both are considered important environmental risk factors. However, a causal relationship remains unproven. OBJECTIVE: To primarily investigate the relationship between body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and smoking and HS, and secondarily to investigate potential relationships between 3 inflammatory diseases (psoriasis, inflammatory bowel disease [IBD], and systemic sclerosis [SSc]) and HS. DESIGN, SETTING, AND PARTICIPANTS: A mendelian randomization (MR) study conducted in 2024 on 5 exposure phenotypes (BMI, smoking, psoriasis, IBD, and SSc) on the outcome of phenotype HS was conducted. The MR analyses used large genetic White European cohorts from genome-wide association studies (GWAS) of each of the 6 phenotypes. Initial analyses were conducted May, 2024, and were updated in May, 2025. EXPOSURE: The 5 exposure phenotypes using predetermined genome-wide significant single-nucleotide variants as proxies for each particular exposure. RESULTS: The GWAS on HS included 4814 case patients and more than 1.2 million controls from Denmark, Iceland, Finland, the UK, and the US. The BMI GWAS involved 700&#x202f;000 individuals from the UK Biobank and GIANT consortium. Smoking data were obtained from 1.23 million participants in an international consortium. The psoriasis GWAS analyzed 39&#x202f;498 case patients and 286&#x202f;769 controls from White European populations and a DNA genetic testing company. The IBD GWAS meta-analysis included 38&#x202f;155 case patients and 48&#x202f;485 controls from the International Inflammatory Bowel Disease (IBD) Genetics Consortium. The SSc GWAS included 9095 case patients and 17&#x202f;584 controls from White European populations. Genetic correlations (rg) were found between HS and all exposure phenotypes except SSc (BMI: rg&#x2009;=&#x2009;0.36, P&#x2009;<&#x2009;.001; smoking: rg&#x2009;=&#x2009;0.33, P&#x2009;<&#x2009;.001; IBD: rg&#x2009;=&#x2009;0.25, P&#x2009;<&#x2009;.001; psoriasis: rg&#x2009;=&#x2009;0.34, P&#x2009;<&#x2009;.001; SSc: rg&#x2009;=&#x2009;0.33, P&#x2009;=&#x2009;.22). MR analyses supported an effect of BMI on HS (&#x3b2;&#x2009;=&#x2009;0.87; odds ratio [OR] per BMI unit, 1.20; 95% CI, 1.17-1.23; P&#x2009;<&#x2009;.001) without signs of pleiotropy (slope: &#x3b2;&#x2009;=&#x2009;0.91, P&#x2009;<&#x2009;.001, P for intercept&#x2009;=&#x2009;.76). Smoking showed a significant causal estimate (&#x3b2;&#x2009;=&#x2009;0.59, P&#x2009;<&#x2009;.001), but results became inconclusive in subsequent sensitivity analyses. Among IBD, psoriasis, and SSc, results supported a causal effect of IBD on HS (&#x3b2;&#x2009;=&#x2009;0.18, OR&#x2009;=&#x2009;1.20; 95% CI, 1.15-1.24; P&#x2009;<&#x2009;.001), without signs of pleiotropy. CONCLUSIONS AND RELEVANCE: These findings indicate causal effects of IBD and increased BMI on the risk of HS. This information may help physicians inform patients about disease risk contributed by modifiable lifestyle behaviors, which can be beneficial for planning lifestyle interventions.

Humans↗

Expression of nitric oxide synthases and formation of nitrotyrosine and reactive oxygen species in inflammatory bowel disease.

Nitric oxide (NO) and reactive oxygen species (ROS) are important mediators in the pathogenesis of inflammatory bowel disease (IBD). NO in IBD can be either harmful or protective. NO can react with superoxide anions (O2.-), yielding the toxic oxidizing agent peroxynitrite (ONOO-). Peroxynitrite induces nitration of tyrosine residues (nitrotyrosine), leading to changes of protein structure and function. The aim of this study was to identify the cellular source of inducible nitric oxide synthase (iNOS) and to localize superoxide anion-producing cells in mucosal biopsies from patients with active IBD. Additional studies were performed to look at nitrotyrosine formation as a measure of peroxynitrite-mediated tissue damage. For this, antibodies against iNOS, endothelial NOS (eNOS), and nitrotyrosine were used. ROS-producing cells were detected cytochemically. Inflamed mucosa of patients with active IBD showed intense iNOS staining in the epithelial cells. iNOS could not be detected in non-inflamed mucosa of IBD patients and control subjects. eNOS was present in blood vessels, without any difference in the staining intensity between IBD patients and control subjects. ROS-producing cells were increased in the lamina propria of IBD patients; a fraction of these cells were CD15-positive. Nitrotyrosine formation was found on ROS-positive cells. These results show that iNOS is induced in epithelial cells from patients with active ulcerative colitis or Crohn's disease. Nitration of proteins was detected only on the ROS-producing cells at some distance from the iNOS-producing epithelial cells. These findings indicate that tissue damage during active inflammation in IBD patients is probably more related to ROS-producing cells than to NO. One may speculate that NO has a protective role when during active inflammation other mucosal defence systems are impaired.

Adult↗

Calcium and 1 alpha,25-dihydroxyvitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease.

Vitamin D-deficient IL-10 knockout (KO) mice develop accelerated inflammatory bowel disease (IBD). Removing dietary calcium from the diets of vitamin D-deficient IL-10 KO mice increased the severity of IBD. The mice fed either calcium or active vitamin D (1 alpha,25-dihydroxyvitamin D3, 1,25D3), developed an intermediate form of IBD, while the mice fed both calcium and 1,25D3 had the mildest form of IBD. TNF-alpha secretion from Con A-stimulated splenocytes was reduced by dietary calcium or 1,25D3 treatment. The IL-10 KO mice that received both high calcium diets and 1,25D3 treatments had the lowest TNF-alpha production. In the colons, a TNF-alpha-inducing transcription factor, LPS-induced TNF-alpha factor (LITAF), was inhibited by 1,25D3, but not by calcium. The inhibition of several TNF-alpha-related genes was associated with the decreased colitis in 1,25D3-treated IL-10 KO mice. Furthermore, fulminating IBD in vitamin D receptor/IL-10 double-KO mice corresponded with the increased expression of TNF-alpha and LITAF in the colon. Our results suggest that dietary calcium has independent effects on IBD severity and that 1,25D3 and high calcium together result in the maximal suppression of experimental IBD. The data support a model where dietary calcium and 1,25D3 treatment directly and indirectly inhibit the TNF-alpha pathway and suppress IBD.

Animals↗

Relationship between ANCA and clinical activity in inflammatory bowel disease: variation in prevalence of ANCA and evidence of heterogeneity.

Antineutrophil cytoplasmic antibodes (ANCA) are markers of necrotizing vasculitis. ANCA have been recently detected in the two forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). To assess the possible role of ANCA in the diagnosis and management of IBD we studied the prevalence of ANCA at diagnosis and during follow-up in a group of 89 IBD patients. The relationship between ANCA and clinical features of IBD was investigated. ANCA assayed by indirect immunofluorescence were detected in 38/52 (73%) of the UC patients but only 6/37 (16.6%) of the CD patients (P<0.005) and in none of the controls. In the UC group, but not in the CD group, there was a positive correlation between ANCA and disease activity. The sensitivity and specificity of ANCA for the diagnosis of UC were 73 and 83.7% respectively. The most commonly observed pattern of ANCA in IBD patients was perinuclear: in 84% of the UC and 66.6% of the CD patients positive for ANCA, respectively. However, careful comparison of IFL patterns revealed some distinct features of IBD-associated ANCA when compared to vasculitis-associated ANCA. In addition, most ANCA positive sera from IBD patients were negative for antibodies to proteinase 3 and myeloperoxidase by ELISA. These results suggest that the autoantigens recognized by ANCA are different in patients with IBD from those with necrotising vasculitis.

Adolescent↗