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Background & Aims: The inflammatory bowel diseases (IBDs) are chronic diseases that often require surgery. However, the risk of requirement of surgery over time has not been well characterized. We performed a systematic review and meta-analysis to establish the cumulative risk of surgery among patients with IBD and evaluated how this risk has changed over time. Methods: We searched Medline, EMBASE, PubMed, and conference proceedings (2009–2012) on May 8, 2013, for terms related to IBD and intestinal surgery. Two reviewers screened 8338 unique citations to identify 486 for full-text review. The analysis included population-based studies published as articles (n = 26) and abstracts (n = 4) that reported risks of surgery at 1, 5, or 10 years after a diagnosis of Crohn's disease and/or ulcerative colitis. The trend in risk of surgery over time was analyzed by meta-regression using mixed-effect models. Results: Based on all population-based studies, the risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease was 16.3% (95% confidence interval [CI], 11.4%–23.2%), 33.3% (95% CI, 26.3%–42.1%), and 46.6% (95% CI, 37.7%–57.7%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of ulcerative colitis was 4.9% (95% CI, 3.8%–6.3%), 11.6% (95% CI, 9.3%–14.4%), and 15.6% (95% CI, 12.5%–19.6%), respectively. The risk of surgery 1, 5, and 10 years after diagnosis of Crohn's disease and 1 and 10 years after diagnosis of ulcerative colitis has decreased significantly over the past 6 decades (P < .05). Conclusions: Based on systematic review and meta-analysis of population-based studies, the risk of intestinal surgery among patients with IBD has decreased over the past 6 decades. [Copyright &y& Elsevier]

The Human Genome Project was completed a decade ago, leaving a legacy of process, tools, and infrastructure now being turned to the study of the microbes that reside in and on the human body as determinants of health and disease, and has been branded “The Human Microbiome Project.” Of the various niches under investigation, the human gut houses the most complex and abundant microbial community and is an arena for important host–microbial interactions that have both local and systemic impact. Initial studies of the human microbiome have been largely descriptive, a testing ground for innovative molecular techniques and new hypotheses. Methods for studying the microbiome have quickly evolved from low-resolution surveys of microbial community structure to high-definition description of composition, function, and ecology. Next-generation sequencing technologies combined with advanced bioinformatics place us at the doorstep of revolutionary insight into the composition, capability, and activity of the human intestinal microbiome. Renewed efforts to cultivate previously “uncultivable” microbes will be important to the overall understanding of gut ecology. There remain numerous methodological challenges to the effective study and understanding of the gut microbiome, largely relating to study design, sample collection, and the number of predictor variables. Strategic collaboration of clinicians, microbiologists, molecular biologists, computational scientists, and bioinformaticians is the ideal paradigm for success in this field. Meaningful interpretation of the gut microbiome requires that host genetic and environmental influences be controlled or accounted for. Understanding the gut microbiome in healthy humans is a foundation for discovering its influence in various important gastrointestinal and nutritional diseases (eg, inflammatory bowel disease, diabetes, and obesity), and for rational translation to human health gains. [ABSTRACT FROM AUTHOR]

Background & Aims: The histopathology of nonalcoholic fatty liver disease (NAFLD) is similar to that of alcoholic liver disease. Colonic bacteria are a source of many metabolic products, including ethanol and other volatile organic compounds (VOC) that may have toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. Recent data suggest that the composition of the gut microbiota in obese human beings is different from that of healthy-weight individuals. The aim of this study was to compare the colonic microbiome and VOC metabolome of obese NAFLD patients (n = 30) with healthy controls (n = 30). Methods: Multitag pyrosequencing was used to characterize the fecal microbiota. Fecal VOC profiles were measured by gas chromatography–mass spectrometry. Results: There were statistically significant differences in liver biochemistry and metabolic parameters in NAFLD. Deep sequencing of the fecal microbiome revealed over-representation of Lactobacillus species and selected members of phylum Firmicutes (Lachnospiraceae; genera, Dorea, Robinsoniella, and Roseburia) in NAFLD patients, which was statistically significant. One member of phylum Firmicutes was under-represented significantly in the fecal microbiome of NAFLD patients (Ruminococcaceae; genus, Oscillibacter). Fecal VOC profiles of the 2 patient groups were different, with a significant increase in fecal ester compounds observed in NAFLD patients. Conclusions: A significant increase in fecal ester VOC is associated with compositional shifts in the microbiome of obese NAFLD patients. These novel bacterial metabolomic and metagenomic factors are implicated in the etiology and complications of obesity. [Copyright &y& Elsevier]

BACKGROUND Mycophenolate mofetil (MMF) is commonly prescribed after transplantation and has major advantages over other immunosuppressive drugs, but frequent gastrointestinal (GI) side-effects limit its use. The mechanism(s) underlying MMF-related GI toxicity have yet to be elucidated. METHODS To investigate MMF-related GI toxicity, experimental mice were fed chow containing MMF (0.563%) and multiple indices of toxicity, including weight loss and colonic inflammation, were measured. Changes in intestinal microbial composition were detected using 16S rRNA Illumina sequencing, and downstream PICRUSt analysis was used to predict metagenomic pathways involved. Germ-free (GF) mice and mice treated with orally administered broad-spectrum antibiotics (ABX) were utilized to interrogate the importance of the microbiota in MMF-induced GI toxicity. RESULTS Mice treated with MMF exhibited significant weight loss, related to loss of body fat and muscle, and marked colonic inflammation. MMF exposure was associated with changes in gut microbial composition, as demonstrated by a loss of overall diversity, expansion of Proteobacteria (specifically Escherichia/Shigella ), and enrichment of genes involved in lipopolysaccharide (LPS) biosynthesis, which paralleled increased levels of LPS in the feces and serum. MMF-related GI toxicity was dependent on the intestinal microbiota, as MMF did not induce weight loss or colonic inflammation in GF mice. Furthermore, ABX prevented and reversed MMF-induced weight loss and colonic inflammation. CONCLUSIONS An intact intestinal microbiota is required to initiate and sustain the GI toxicity of MMF. MMF treatment causes dynamic changes in the composition of the intestinal microbiota that may be a targetable driver of the GI side-effects of MMF. [ABSTRACT FROM AUTHOR]

Giardia duodenalis is a prevalent cause of acute diarrheal disease worldwide. However, recent outbreaks in Italy and Norway have revealed a link between giardiasis and the subsequent development of chronic post-infectious irritable bowel syndrome. While the mechanisms underlying the causation of post-infectious irritable bowel syndrome remain obscure, recent findings suggest that alterations in gut microbiota communities are linked to the pathophysiology of irritable bowel syndrome. In the present study, we use a laboratory biofilm system to culture and enrich mucosal microbiota from human intestinal biopsies. Subsequently, we show that co-culture with Giardia induces disturbances in biofilm species composition and biofilm structure resulting in microbiota communities that are intrinsically dysbiotic – even after the clearance of Giardia . These microbiota abnormalities were mediated in part by secretory-excretory Giardia cysteine proteases. Using in vitro cell culture and germ-free murine infection models, we show that Giardia -induced disruptions of microbiota promote bacterial invasion, resulting in epithelial apoptosis, tight junctional disruption, and bacterial translocation across an intestinal epithelial barrier. Additionally, these dysbiotic microbiota communities resulted in increased activation of the Toll-like receptor 4 signalling pathway, and overproduction of the pro-inflammatory cytokine IL-1beta in humanized germ-free mice. Previous studies that have sought explanations and risk factors for the development of post-infectious irritable bowel syndrome have focused on features of enteropathogens and attributes of the infected host. We propose that polymicrobial interactions involving Giardia and gut microbiota may cause persistent dysbiosis, offering a new interpretation of the reasons why those afflicted with giardiasis are predisposed to gastrointestinal disorders post-infection. [ABSTRACT FROM AUTHOR]

Background Malabsorptive etiologies of chronic diarrhea are important to identify. The 72-h stool for fecal fat test (FFT), the gold standard for diagnosing fat malabsorption, is fraught with limitations that impact its reliability. Vitamin A, a fat-soluble vitamin, parallels the absorption of lipids. We assessed the feasibility and validate a novel clinical test, retinyl palmitate (RP), for the diagnosis of fat malabsorption, and to compare the results to the FFT. Methods Using a case-control study design, patients with chronic diarrhea secondary to suspected malabsorption, and healthy control subjects were identified. A Dietitian taught subjects to consume a 100 g fat diet for the FFT with measurements of stool fat after 72-h. Serum levels of Vitamin A (retinol) and RP were measured by reversed-phase high pressure liquid chomatography. Two-way comparisons were made between the groups using 2 sample Wilcoxon rank-sum tests. Results Sixteen patients completed this study (8 cases and 8 control subjects). Fecal fat results were available for 15/16 patients. The sensitivity of the FFT was 100% (identified all cases), but the FFT specificity was 42%, as 4/7 control patients were identified as malabsorbers. Cases with short bowel syndrome had the lowest RP levels but this did not meet statistical significance. There was no significant difference for serum RP levels when comparing cases and control patients' AUC. Conclusions Serum RP is useful to identify malabsorption, albeit in severe cases. Furthermore, we have shown that the 72-hour FFT has poor performance characteristics, highlighting the need for more useful diagnostics in identifying malabsorption. [ABSTRACT FROM AUTHOR]

Abstract Objectives: Administering proton pump inhibitors (PPI) intravenously (iv) after endoscopic treatment of bleeding peptic ulcers reduces the incidence of rebleeding, the need for operative procedures, and hospitalizations. We assessed the cost implications of iv PPI initiated in all patients presenting to the emergency department (ED) with signs of upper gastrointestinal (UGI) bleeding. Methods: From a third-party payer perspective with a time horizon of 60 days, we built a decision analytic model comparing standard endoscopic therapy to a strategy in which all patients presenting to the ED with UGI bleeding would start iv PPI before endoscopy. After endoscopy, only those with peptic ulcers would be kept on iv PPI added to standard therapy. Probabilities of health events were extracted from published literature. Resource utilization profiles and costs (iv PPI, hospital stay for medical and operative procedures, and professional fees) were based on Medicare reimbursement data from a large hospital in Alabama. All costs were expressed in 2000 US dollars. Uncertainty was investigated through one-way sensitivity analyses and probabilistic analyses using Monte Carlo simulations. Results: In a hypothetical group of 1000 individuals, routine use of iv PPI prevented 40 rebleeds, 9 surgical procedures, and 223 hospital days, and led to incremental savings of $920 per subject. Probabilistic sensitivity analyses indicated that the strategy of using iv PPI was likely to be dominant even when accounting for uncertainty. Conclusions: Based on available evidence, routine administration of iv PPI to all persons presenting with UGI bleeding represents good value for money and merits consideration as standard hospital policy. [ABSTRACT FROM AUTHOR]