SciCombinator

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Concept: Gastroenterology

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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.

Concepts: Inflammation, Gut flora, Gastroenterology, Immune system, Nutrition, Ulcerative colitis, Inflammatory bowel disease, Bacteria

218

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.

Concepts: Cohort study, Demography, Gastroenterology, Diabetes mellitus type 2, Ulcerative colitis, Inflammation, Inflammatory bowel disease, Epidemiology

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We present bacterial biogeography as sampled from the human gastrointestinal tract of four healthy subjects. This study generated >32 million paired-end sequences of bacterial 16S rRNA genes (V3 region) representing >95,000 unique operational taxonomic units (OTUs; 97% similarity clusters), with >99% Good’s coverage for all samples. The highest OTU richness and phylogenetic diversity was found in the mouth samples. The microbial communities of multiple biopsy sites within the colon were highly similar within individuals and largely distinct from those in stool. Within an individual, OTU overlap among broad site definitions (mouth, stomach/duodenum, colon and stool) ranged from 32-110 OTUs, 25 of which were common to all individuals and included OTUs affiliated with Faecalibacterium prasnitzii and the TM7 phylum. This first comprehensive characterization of the abundant and rare microflora found along the healthy human digestive tract represents essential groundwork to investigate further how the human microbiome relates to health and disease.

Concepts: Ribosomal RNA, Archaea, 16S ribosomal RNA, Microbiology, Gastroenterology, Human gastrointestinal tract, Digestion, Digestive system

185

It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.

Concepts: Probiotic, Gut flora, Digestive system, Flatulence, Irritable bowel syndrome, Immune system, Gastroenterology, Bacteria

169

To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.

Concepts: Small intestine, Large intestine, Ileocecal valve, Small bowel bacterial overgrowth syndrome, Digestive system, Intestine, Gastroenterology, Bacteria

169

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.

Concepts: Normal distribution, Malabsorption, Gastroenterology, Epidemiology, Ulcerative colitis, Crohn's disease, Cancer, Hospital

168

Upper gastrointestinal (GI) bleeding is one of the most common, high risk emergency disorders in the western world. Almost nothing has been reported on longer term prognosis following upper GI bleeding. The aim of this study was to establish mortality up to three years following hospital admission with upper GI bleeding and its relationship with aetiology, co-morbidities and socio-demographic factors.

Concepts: Central Europe, Western Europe, Surgery, Western culture, Gastrointestinal bleeding, Western world, Gastroenterology, Upper gastrointestinal bleeding

168

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.

Concepts: Psychometrics, Health care provider, Patient, Gastroenterology, Ulcerative colitis, Inflammation, Inflammatory bowel disease, Irritable bowel syndrome

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Alagille syndrome (AS) is a multisystemic disease autosomal dominant, with variable expression. The major clinical manifestations are: chronic cholestasis, congenital heart disease, posterior embryotoxon in the eye, characteristic facial phenotype, and butterfy vertebrae. AS is caused by mutations in JAGGED1 (more than 90%) and in NOTCH2. Differential diagnosis include: infections, genetic-metabolic diseases, biliary atresia, idiopathic cholestasis. Cholestasis, pruritus and xanthomas have been successfully treated with choleretic agents (ursodeoxycholic acid) and other medications (cholestyramine, rifampin, naltrexone). In certain cases, partial external biliary diversion has also proved successful. Liver transplantation is indicated in children with cirrhosis and liver failure.

Concepts: Alagille syndrome, Medicine, Progressive familial intrahepatic cholestasis, Cancer, Medical terms, Gastroenterology, Liver, Hepatology