Gut microbiome in primary sclerosing cholangitis:A review

Primary sclerosing cholangitis(PSC)is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing.Exploration of the pathogenesis of PSC in light of its association with inflammatory bowel disease(IBD)and the“gut-liver”axis is an emerging area of interest.A growing number of studies have begun to elucidate the role of the gut microbiota,its metabolites and its influence on host immune responses in the development of PSC and PSCIBD.Studies of the fecal microbiota have highlighted enriched levels of certain species,including Veillonella,Streptococcus and Enterococcus,among others.A heightened immune response to enteric dysbiosis and bacterial translocation have also been implicated.For example,Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 responses.Gut microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites,including bile acids(BAs),which function as signaling molecules with important gut and hepatic effects.An expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions,such as antibiotics,nutritional interventions and fecal microbial transplantation.Some of these have already shown some preliminary evidence of benefit.Despite exciting progress in the field,much work remains to be done;areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric populations.In this review,we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms,including the potential role of metabolites,such as BAs.We then briefly review the evidence for interventions with microbe-altering properties for treating PSC.

Assessing disease activity using the pediatric Crohn’s disease activity index:Can we use subjective or objective parameters alone?

BACKGROUND The pediatric Crohn’s disease activity index(PCDAI)is used as a standard tool to assess disease activity in clinical trials for pediatric Crohn’s disease.AIM To examine which items on the PCDAI drive assessment of disease activity,and how subgroups of subjective and objective items reflect change in disease state over time.METHODS Selective raw data from three prospectively collected datasets were combined,including 703 children with full PCDAI data at baseline,at 3-mo(Q1,n=670),and 1-year(Q4,n=474).Change in individual PCDAI scores from baseline to Q1 and to Q4 were examined using the non-weighted PCDAI.RESULTS Abdominal pain,well-being,weight,and stooling had the highest change scores over time.Objective indicators including albumin,abdominal exam,and height velocity followed.Change scores for well-being and abdominal exam did not explain significant variance at Q1 but were significant predictors at Q4(P<0.001 and P<0.05).Subjective and objective subgroups of items predicted less variance(18%and 22%)on total PCDAI scores at Q1 and Q4 compared to the full PCDAI,or a composite scale(both 32%)containing significant predictors.CONCLUSION Although subjective items on the PCDAI change the most over time,the full PCDAI or a smaller composite of items including a combination of subjective and objective components classifies disease activity better than a subgroup of either subjective or objective items alone.Reliance on subjective or objective items as stand-alone proxies for disease activity measurement could result in misclassification of disease state.