Anti-inflammatory effects of a casein hydrolysate and its peptide-enriched fractions on TNFα-challenged Caco-2 cells and LPS-challenged porcine colonic explants

Bioactive milk peptides are reported to illicit a range of physiological benefits and have been proposed as potential functional food ingredients. The objective of this study was to characterize the anti-inflammatory properties of sodium caseinate (NaCAS), its enzyme hydrolysate (EH) and peptide-enriched fractions (5 kDa retentate [R], 1 kDaR and 1 kDa permeate [P]), both in vitro using a Caco-2 cell line, and also ex vivo using a porcine colonic tissue explant system. Caco-2 cells were stimulated with tumour necrosis factor alpha (TNFα) and co-treated with casein hydrolysates for 24 h. Following this, interleukin (IL)-8 concentrations in the supernatant were measured using enzyme-linked immunosorbent assay. Porcine colonic tissue was stimulated with lipopolysaccharide and co-treated with casein hydrolysates for 3 h. The expression of a panel of inflammatory cytokines was measured using qPCR. While dexamethasone reduced the IL-8 concentration by 41.6%, the 1 kDaR and 1 kDaP fractions reduced IL-8 by 68.7% and 66.1%, respectively, relative to TNFα-stimulated Caco-2 cells (P < 0.05). In the ex vivo system, only the 1 kDaR fraction elicited a decrease in IL1-α, IL1-β, IL-8, TGF-β and IL-10 expression (P < 0.05). This study provides evidence that the bioactive peptides present in the 1 kDaR fraction of the NaCAS hydrolysate possess anti-inflammatory properties in vitro and ex vivo. Further in vivo analysis of the anti-inflammatory properties of the 1 kDaR is proposed

A comprehensive evaluation of colonic mucosal isolates of Sutterella wadsworthensis from inflammatory bowel disease

Peer reviewedPublisher PD

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

&lt;p&gt;Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.&lt;/p&gt; &lt;p&gt;Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.&lt;/p&gt; &lt;p&gt;Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).&lt;/p&gt; &lt;p&gt;Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.&lt;/p&gt

Investigation of a hepatitis A outbreak in children in an urban slum in Vellore,Tamil Nadu, using geographic information systems

Background &amp; objectives: An outbreak of symptomatic viral hepatitis in children less than 10 yr of age in Vellore, south India, was investigated and the disease pattern studied using serological and epidemiological methods, supplemented by geographic information systems (GIS) mapping. Methods: Three cases of hepatitis A were identified during routine surveillance in a birth cohort House-to-house visits were undertaken to identify other symptomatic cases and samples collected for anti- HAV IgM, ELISA testing. All cases and controls were mapped and geo-referenced using Arc View GIS 3.3. Spatial clustering was investigated using SaTScan 7.0.1 software. Drinking water sources were tested for coliform counts with the most probable number technique. Results: Of the 965 children surveyed, 26 (2.78%) had jaundice between February to July 2006. From the 26 patients, 11 (42.3%) blood samples were obtained and tested for anti-HAV IgM; 10 (90.9%) were found to be positive. Water analysis showed high coliform counts in all samples. No spatial clustering of cases could be detected. Interpretation &amp; conclusions: The outbreak was identified because of the symptomatic presentation of the cases. Our study highlighted the increasing detection of symptomatic children with hepatitis A virus infection. Water sources in the area were contaminated and may have served as the source of infection. The lack of clustering in GIS analysis could be due to the common water source

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

Sensitivity analysis for joint inversion of ground-penetratingradar and thermal-hydrological data from a large-scale underground heatertest

We describe a joint inversion approach that combinesgeophysical and thermal-hydrological data for the estimation of (1)thermal-hydrological parameters (such as permeability, porosity, thermalconductivity, and parameters of the capillary pressure and relativepermeability functions) that are necessary for predicting the flow offluids and heat in fractured porous media, and (2) parameters of thepetrophysical function that relates water saturation, porosity andtemperature to the dielectric constant. The approach incorporates thecoupled simulation of nonisothermal multiphase fluid flow andground-penetrating radar (GPR) travel times within an optimizationframework. We discuss application of the approach to a large-scale insitu heater test which was conducted at Yucca Mountain, Nevada, to betterunderstand the coupled thermal, hydrological, mechanical, and chemicalprocesses that may occur in the fractured rock mass around a geologicrepository for high-level radioactive waste. We provide a description ofthe time-lapse geophysical data (i.e., cross-borehole ground-penetratingradar) and thermal-hydrological data (i.e., temperature and water contentdata) collected before and during the four-year heating phase of thetest, and analyze the sensitivity of the most relevantthermal-hydrological and petrophysical parameters to the available data.To demonstrate feasibility of the approach, and as a first step towardcomprehensive inversion of the heater test data, we apply the approach toestimate one parameter, the permeability of the rock matrix

Investigation of the Enteric Pathogenic Potential of Oral Campylobacter concisus Strains Isolated from Patients with Inflammatory Bowel Disease

BACKGROUND: Campylobacter concisus, a bacterium colonizing the human oral cavity, has been shown to be associated with inflammatory bowel disease (IBD). This study investigated if patients with IBD are colonized with specific oral C. concisus strains that have potential to cause enteric diseases. METHODOLOGY: Seventy oral and enteric C. concisus isolates obtained from eight patients with IBD and six controls were examined for housekeeping genes by multilocus sequence typing (MLST), Caco2 cell invasion by gentamicin-protection-assay, protein analysis by mass spectrometry and SDS-PAGE, and morphology by scanning electron microscopy. The whole genome sequenced C. concisus strain 13826 which was isolated from an individual with bloody diarrhea was included in MLST analysis. PRINCIPAL FINDINGS: MLST analysis showed that 87.5% of individuals whose C. concisus belonged to Cluster I had inflammatory enteric diseases (six IBD and one with bloody diarrhea), which was significantly higher than that in the remaining individuals (28.6%) (P<0.05). Enteric invasive C. concisus (EICC) oral strain was detected in 50% of patients with IBD and none of the controls. All EICC strains were in Cluster 1. The C. concisus strain colonizing intestinal tissues of patient No. 1 was closely related to the oral C. concisus strain from patient No. 6 and had gene recombination with the patient's own oral C. concisus. The oral and intestinal C. concisus strains of patient No. 3 were the same strain. Some individuals were colonized with multiple oral C. concisus strains that have undergone natural recombination. CONCLUSIONS: This study provides the first evidence that patients with IBD are colonized with specific oral C. concisus strains, with some being EICC strains. C. concisus colonizing intestinal tissues of patients with IBD at least in some instances results from an endogenous colonization of the patient's oral C. concisus and that C. concisus strains undergo natural recombination

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n1⁄42,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n1⁄43,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombinedo5108) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist