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Background Fecal calprotectin (fCAL) is a noninvasive biomarker used to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Methods A multicenter prospective case–control study evaluating the BÜHLMANN fCAL enzyme-linked immunosorbent assay (ELISA) was conducted in 478 subjects. Sensitivity, specificity, predictive values, and area under the receiver operator characteristic (AuROC) curve are reported and compared to another device. Results In differentiating IBD from IBS, the BÜHLMANN fCAL ELISA is very sensitive (93.3%) at a cutoff 160 μg/g (AuROC 0.933). Conclusions The BÜHLMANN fCAL ELISA demonstrates excellent discriminating between IBD and IBS.

Currently, standard protocols for microbial DNA extraction from intestinal tissues do not exist. We assessed the efficiency of a commercial kit with and without mechanical disruption. Better quality DNA was obtained without mechanical disruption. Thus, it appears that bead-beating is not required for efficient microbial DNA extraction from intestinal biopsies.

This study used 16S rRNA-based pyrosequencing to examine the microbial community that is closely associated with the colonic mucosa of five healthy individuals. Spatial heterogeneity in microbiota was measured at right colon, left colon and rectum, and between biopsy duplicates spaced 1 cm apart. The data demonstrate that mucosal-associated microbiota is comprised of Firmicutes (50.9% ± 21.3%), Bacteroidetes (40.2% ± 23.8%) and Proteobacteria (8.6%± 4.7%), and that interindividual differences were apparent. Among the genera, Bacteroides, Leuconostoc and Weissella were present at high abundance (4.6% to 41.2%) in more than 90% of the studied biopsy samples. Lactococcus, Streptococcus, Acidovorax, Acinetobacter, Blautia, Faecalibacterium, Veillonella, and several unclassified bacterial groups were also ubiquitously present at an abundance

Hydrogenotrophic microbiota have a significant impact on colonic health; however, little is known about their diversity and ecology in situ. Here, molecular-based methods and multivariate analyses were used to examine the abundance and diversity of mucosa-associated hydrogenotrophic microbes in 90 biopsies collected from right colon, left colon and rectum of 25 healthy subjects. Functional genes of all three hydrogenotrophic groups were detected in at least one colonic region of all subjects. Methanogenic archaea (MA) constituted approximately one half of the hydrogenotrophic microbiota in each colonic region. Sulfate-reducing bacteria (SRB) were more abundant than acetogens in right colon, while acetogens were more abundant than SRB in left colon and rectum. MA genotypes exhibited low diversity, whereas SRB genotypes were diverse and generally similar across the three regions within subject but significantly variable among subjects. Multivariate cluster analysis defined subject-specific patterns for the diversity of SRB genotypes; however, neither subject- nor region-specific clusters were observed for the abundance of hydrogenotrophic functional genes. Sequence analyses of functional gene clones revealed that mucosa-associated SRB were phylogenetically related to Desulfovibrio piger, Desulfovibrio desulfuricans and Bilophila wadsworthia; whereas MA were related to Methanobrevibacter spp., Mb. smithii and the order Methanomicrobiales. Together these data demonstrate for the first time that the human colonic mucosa is persistently colonized by all three groups of hydrogenotrophic microbes, which exhibit segmental and interindividual variation in abundance and diversity.

The colonic mucus layer is comprised primarily of acidomucins, which provide viscous properties and can be broadly classified into sialomucins or sulfomucins based on the presence of terminating sialic acid or sulfate groups. Differences in acidomucin chemotypes have been observed in diseases such as colorectal cancer and inflammatory bowel disease, and variation in sialo- and sulfomucin content may influence microbial colonization. For example, sulfate derived from sulfomucin degradation may promote the colonization of sulfate-reducing bacteria (SRB), which through sulfate respiration generate the genotoxic gas hydrogen sulfide. Here, paired biopsies from right colon, left colon, and rectum of 20 subjects undergoing routine screening colonoscopies were collected to enable parallel histochemical and microbiological studies. Goblet cell sialo- and sulfomucins in each biopsy were distinguished histochemically and quantified. Quantitative PCR and multivariate analyses were used to examine the abundance of hydrogenotrophic microbial groups and SRB genera relative to acidomucin profiles. Regional variation was observed in sialomucins and sulfomucins with the greatest abundance of each found in the rectum. Mucin composition did not appear to influence the abundance of SRB or other hydrogenotrophic microbiota but correlated with the composition of different SRB genera. A higher sulfomucin proportion correlated with higher quantities of Desulfobacter, Desulfobulbus and Desulfotomaculum, relative to the predominant Desulfovibrio genus. Thus, acidomucin composition may influence bacterial sulfate respiration in the human colon, which may in turn impact mucosal homeostasis. These results stress the need to consider mucus characteristics in the context of studies of the microbiome that target intestinal diseases.

A 52-year-old woman was referred to the gastroenterology clinic for evaluation of abdominal pain and a change in her bowel habits. The patient reported an eight-week history of colicky postprandial pain in her right lower quadrant that did not radiate and episodic vomiting in association with the

Intraductal papillary mucinous tumors (IPMT) are known to occur in the pancreas but rarely can occur in the bile ducts. These tumors secrete mucin that may form mucous plugs resulting in biliary stasis, biliary duct obstruction and dilation. We report a case of IPMT of the biliary tract that presented with fatigue and a persistent cholestatic pattern of liver enzyme elevation and required a high index of suspicion to make the final diagnosis. The early recognition and treatment of these tumors is important, as unlike other bile duct tumors, these have a good prognosis.

Background & Aims: This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas. Methods: The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg · kg −1 · day −1 or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of ≥50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks. Results: Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients ( P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients ( P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction. Conclusions: Oral tacrolimus 0.2 mg · kg −1 · day −1 is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated.

Background: Inflammatory bowel diseases (IBD) include Crohn disease and ulcerative colitis, which have become highly prevalent in developed countries around the world. The peak incidence of the disorders is in young adulthood. While the etiology of IBD is not known, an environmentally triggered exaggerated immune response against the intestinal microbiome is thought to mediate the diseases. The rapid emergence of IBD in the past decades has directed attention towards the potential dietary origins of the disease group. We examined how prenatal nutritional programming may impact predilection towards IBD in a murine model. Methods: C57Bl/6J mice were used. Dams were on control or methyl donor micronutrient (MD) supplemented diets. Offspring were cross-fostered between these dams and subsequently weaned to a control diet. At 90 days of life (young adulthood) chemical colitis was induced by dextran sulfate sodium (DSS). Colonic mucosal Ppar-alpha (Ppara) expression was examined with real time RT-PCR in DSS Naive cross-fostered mice. Colonic mucosal and cecal content microbiomes were interrogated with 454 based pyrosequencing of the 16S rRNA gene. The microbiome changes were tested functionally by colonizing germ free Swiss-Webster mice and exposing those to DSS colitis. Results: Prenatal MD supplementation was sufficient to modulate mucosal Ppara expression and worsen acute colitis in young adulthood. The prenatal dietary intervention induced the postnatal nurturing of a colitogenic microbiome. Conclusions: This is the first study to conclusively show that prenatal nutritional programming can modulate the mammalian host to harbor a colitogenic microbiome. These findings may be relevant for the nutritional developmental origins of IBD

Excerpt In 1960 Naish and coworkers reported on a patient with recurrent episodes of intestinal obstruction associated with steatorrhea in whom no organic cause for the obstruction was found. The m...