To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis(PSC)and ulcerative colitis(UC).METHODSStool samples were collected and relevant clinical data obtained from 106 study partic...To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis(PSC)and ulcerative colitis(UC).METHODSStool samples were collected and relevant clinical data obtained from 106 study participants,43 PSC patients with(n=32)or without(n=11)concomitant inflammatory bowel disease,32 UC patients,and 31 healthy controls.The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels.Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data.RESULTSMicrobial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition.Rothia,Enterococcus,Streptococcus,Veillonella,and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease(IBD).Rothia,Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa,Streptococcus infantus,S.alactolyticus,and S.equi along with Veillonella parvula and V.dispar.PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri.Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype.Akkermansia muciniphila,Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia.Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales.CONCLUSIONPSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes(PSC-IBD and UC).展开更多
AIM:To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis(UC) and primary sclerosing cholangitis(PSC) before and after transplantation.METHODS:Eigh...AIM:To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis(UC) and primary sclerosing cholangitis(PSC) before and after transplantation.METHODS:Eight patients with UC and PSC prior to liver transplantation(PSC-UC),22 patients with UC after liver transplantation for PSC(OLT),9 patients with active ulcerative colitis without PSC(UCA),7 patients withUC in remission(UCR) and 10 controls(N) underwent colonoscopy with multiple biopsies.Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53,Bcl-2 and cyclooxygenase-2(COX-2) markers.Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests.RESULTS:PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT,UCA,UCR and N(P < 0.05).We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53(P < 0.001).UCA had a higher p53 expression as compared to UCR.OLT had a significantly lower expression of p53 as compared with PSC-UC(P < 0.001).Bcl-2 had a significant higher bcl-2 expression as compared with controls.No difference in COX-2 expression between PSC-UC,UCR and UCA was found.UCA had higher COX-2 expression as compared to UCR.We also found a statistically significant positive correlation between the expression of COX-2 and p53.Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSCUC(P < 0.001).PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score.CONCLUSION:Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53,suggesting a higher susceptibility of cancer.This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.展开更多
BACKGROUND Ulcerative colitis(UC)with concomitant primary sclerosing cholangitis(PSC)represents a distinct disease entity(PSC-UC).Mayo endoscopic subscore(MES)is a standard tool for assessing disease activity in UC bu...BACKGROUND Ulcerative colitis(UC)with concomitant primary sclerosing cholangitis(PSC)represents a distinct disease entity(PSC-UC).Mayo endoscopic subscore(MES)is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.AIM To assess the accuracy of MES in UC and PSC-UC patients,we performed histological scoring using Nancy histological index(NHI).METHODS MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy.NHI and inflammation were evaluated in biopsies from the cecum,rectum,and terminal ileum.In addition,perinuclear anti-neutrophil cytoplasmic antibodies,fecal calprotectin,body mass index,and other relevant clinical characteristics were collected.RESULTS The median MES and NHI were similar for UC patients(MES grade 2 and NHI grade 2 in the rectum)but were different for PSC-UC patients(MES grade 0 and NHI grade 2 in the cecum).There was a correlation between MES and NHI for UC patients(Spearman's r=0.40,P=0.029)but not for PSC-UC patients.Histopathological examination revealed persistent microscopic inflammation in 88%of PSC-UC patients with MES grade 0(46%of all PSC-UC patients).Moreover,MES overestimated the severity of active inflammation in an additional 11%of PSCUC patients.CONCLUSION MES insufficiently identifies microscopic inflammation in PSC-UC.This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.展开更多
基金Supported by Ministry of Health of the Czech Republic,No.15-28064A
文摘To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis(PSC)and ulcerative colitis(UC).METHODSStool samples were collected and relevant clinical data obtained from 106 study participants,43 PSC patients with(n=32)or without(n=11)concomitant inflammatory bowel disease,32 UC patients,and 31 healthy controls.The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels.Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data.RESULTSMicrobial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition.Rothia,Enterococcus,Streptococcus,Veillonella,and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease(IBD).Rothia,Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa,Streptococcus infantus,S.alactolyticus,and S.equi along with Veillonella parvula and V.dispar.PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri.Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype.Akkermansia muciniphila,Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia.Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales.CONCLUSIONPSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes(PSC-IBD and UC).
基金Supported by IGA Ministry of Health,Czech Republic,No.7878/3
文摘AIM:To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis(UC) and primary sclerosing cholangitis(PSC) before and after transplantation.METHODS:Eight patients with UC and PSC prior to liver transplantation(PSC-UC),22 patients with UC after liver transplantation for PSC(OLT),9 patients with active ulcerative colitis without PSC(UCA),7 patients withUC in remission(UCR) and 10 controls(N) underwent colonoscopy with multiple biopsies.Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53,Bcl-2 and cyclooxygenase-2(COX-2) markers.Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests.RESULTS:PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT,UCA,UCR and N(P < 0.05).We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53(P < 0.001).UCA had a higher p53 expression as compared to UCR.OLT had a significantly lower expression of p53 as compared with PSC-UC(P < 0.001).Bcl-2 had a significant higher bcl-2 expression as compared with controls.No difference in COX-2 expression between PSC-UC,UCR and UCA was found.UCA had higher COX-2 expression as compared to UCR.We also found a statistically significant positive correlation between the expression of COX-2 and p53.Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSCUC(P < 0.001).PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score.CONCLUSION:Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53,suggesting a higher susceptibility of cancer.This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.
基金Supported by Grant Agency of the Ministry of Health of the Czech Republic,No.NV17-31538AGrant Agency of the Czech Republic No.20-16520Y and No.21-21736SMinistry of Education,Youth and Sports of the Czech Republic Project,No.LX22NPO05102.
文摘BACKGROUND Ulcerative colitis(UC)with concomitant primary sclerosing cholangitis(PSC)represents a distinct disease entity(PSC-UC).Mayo endoscopic subscore(MES)is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.AIM To assess the accuracy of MES in UC and PSC-UC patients,we performed histological scoring using Nancy histological index(NHI).METHODS MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy.NHI and inflammation were evaluated in biopsies from the cecum,rectum,and terminal ileum.In addition,perinuclear anti-neutrophil cytoplasmic antibodies,fecal calprotectin,body mass index,and other relevant clinical characteristics were collected.RESULTS The median MES and NHI were similar for UC patients(MES grade 2 and NHI grade 2 in the rectum)but were different for PSC-UC patients(MES grade 0 and NHI grade 2 in the cecum).There was a correlation between MES and NHI for UC patients(Spearman's r=0.40,P=0.029)but not for PSC-UC patients.Histopathological examination revealed persistent microscopic inflammation in 88%of PSC-UC patients with MES grade 0(46%of all PSC-UC patients).Moreover,MES overestimated the severity of active inflammation in an additional 11%of PSCUC patients.CONCLUSION MES insufficiently identifies microscopic inflammation in PSC-UC.This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.
