Concept: Ulcerative colitis
The efficacy and safety of vedolizumab, a humanized immunoglobulin G1 monoclonal antibody against the integrin α4β7, was demonstrated in multicenter, phase 3, randomized, placebo-controlled trials in patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease. We analyzed data from 1 of these trials to determine the effects of vedolizumab therapy in patients with UC, based on past exposure to anti-tumor necrosis factor (TNF) agents.
The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD). Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states) on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled smoking cessation.
To assess whether the use of dipeptidyl peptidase-4 inhibitors is associated with the incidence of inflammatory bowel disease in patients with type 2 diabetes.
To determine the effect of the specific carbohydrate diet (SCD) on active inflammatory bowel disease (IBD).
Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T(H)1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.
Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.
fifteen percent of patients with Crohn’s disease (CD) are elderly; they are less likely to have complications and more likely to have colonic disease.
The role of the gut microbiome in human health and disease with a particular emphasis on therapeutic use of probiotics under specific medical conditions was mainly highlighted in 1st Annual conference of Probiotic Association of India (PAi) and International Symposium on “Probiotics for Human Health - New Innovations and Emerging Trends” held on 27th-28th August, 2012 at New Delhi, India. There is increasing recognition of the fact that dysbiosis or alteration of this gut microbiome may be implicated in gastro-intestinal disorders including diarrheal diseases, ulcerative colitis, inflammatory bowel diseases, life style diseases viz. Diabetes Mellitus-2 and obesity etc. This report summarizes the proceedings of the conference and the symposium comprehensively. Although, research on probiotics has been continuing for the past few decades, the subject has been currently the major focus of attention across the world due to recent advances and new developments in genomics, transcriptomics, proteomics, metabolomics and emergence of new generation of high through put sequencing technologies that have immensely helped in understanding the probiotic functionality and mode of action from nutritional and health perspectives. There is now sufficient evidence backed up with good quality scientific clinical data to suggest that probiotic interventions could indeed be effective in various types of diarrheal diseases, other chronic gastrointestinal inflammatory disorders like pouchitis, necrotizing entero-colitis, allergic responses and lactose intolerance etc. This report makes a modest attempt to give all the stake holders involved in development of probiotic based functional/health foods an overview of the current status of probiotics research at the Global and National level. The most crucial issues that emerged from the lead talks delivered by the eminent speakers from India and abroad were the major focus of discussions in different plenary and technical sessions. By discussing some of these issues from scientific perspectives, the conference could achieve its prime objective of disseminating the current knowledge on the prospects of probiotics as potential biotherapeutics in the management of human health and diseases.
BACKGROUND & AIMS: Little is known about the long-term outcomes of patients with Crohn’s disease (CD) who have a complete response to therapy with azathioprine. We assessed the long-term effects of azathioprine in responders. METHODS: We collected data from the MICISTA registry (a database from the Rothschild and Saint-Antoine Hospitals in Paris, France) on consecutive CD patients treated with azathioprine 1987-1999 who responded to therapy (steroid-free clinical remission at 1 year); they were followed until 2011 (n=220; 86 male; median age 32 years; median follow-up period, 12.6 years). Data were compared with those from 440 matched patients with CD who did not receive immunosuppressants during the same period of inclusion (controls). RESULTS: The cumulative rate of sustained remission 10 years after treatment with azathioprine was 3%. Among patients exposed to azathioprine during a prospective follow-up period (1995-2011, 1936 patient-years), the percent of patient-years with active disease (flare or complication during the calendar year) was 17.6%. Compared to the control group, at baseline, responders were more often active smokers with significantly more extensive disease, perianal lesions, and extra-digestive manifestations. During follow-up, responders had a significantly reduced risk of intestinal surgery (adjusted odds ratio [AOR], 0.69; 95% confidence interval [CI], 0.52-0.91) and of perianal surgery (AOR, 0.36; 95% CI, 0.27-0.46). A significantly higher percentage of responders developed cancers, including non-melanoma skin cancers, compared with controls (9.5% vs 4.1%;P <.01). Survival rates after 20 years were 92.8%±2.3% of responders vs 97.9%±0.8% of controls ( P =.01). CONCLUSION: Based on a study at a single center, patients with CD that responds to azathioprine have a smaller proportion of patient-years with active disease, and are less likely to be hospitalized or undergo intestinal surgery, than patients with CD who did not receive immunosuppressants. These benefits, however, could be offset by increased risk of malignancies.
BACKGROUND: Previous research has suggested an interaction between personality factors and inflammatory bowel disease (IBD) as well as irritable bowel syndrome (IBS). We therefore aimed to elucidate differences in psychological and coping functioning between patients with IBD and IBS, and to assess the relationship of disease activity with these functions. METHODS: Seventy-four patients with IBD (mean age 43±17years, range 18-82years) and 81 patients with IBS (mean age 37±12years, range 21-66years) completed the questionnaires; Rosenberg Self-Esteem Scale, Toronto Alexithymia, Experiences in Close Relationships, and Sense of Coherence. Disease activity was evaluated either by the Harvey-Bradshaw index, the Simple Clinical Colitis Activity Index, or the Visual Analogue Scale for Irritable Bowel Syndrome. RESULTS: The study revealed that patients with IBS had higher degree of anxiety in close relationships than patients with IBD (p=0.003), and lower self-esteem (p=0.001). No other statistical differences between the whole groups IBS and IBD or between subgroups were seen. CONCLUSIONS: The fact that patients with IBS seem to have higher levels of anxiety in relationships and lower self-esteem could influence the way the patient deal with the disease and how the communication with health care professionals works out. A higher awareness of the importance of past negative life events should be taken into consideration. Whether the disease or the personal traits are the primary event should be addressed in future research.