scholarly journals Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ramon V. Cortez ◽  
Luana N. Moreira ◽  
Marina Padilha ◽  
Mariana D. Bibas ◽  
Ricardo K. Toma ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Pediatric Patients ◽  
Total Bilirubin ◽  
Intestinal Microbiome ◽  
Gamma Glutamyl Transferase ◽  
Microbiome Composition ◽  
Gamma Glutamyl ◽  
Glutamyl Transferase

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients’ age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

scholarly journals Tissue-dependent transcriptional and bacterial associations in primary sclerosing cholangitis-associated inflammatory bowel disease

2021 ◽  
Vol 6 ◽  
pp. 199
Author(s):  
Nicholas E. Ilott ◽  
Mastura Neyazi ◽  
Carolina V. Arancibia-Cárcamo ◽  
Fiona Powrie ◽  
Alessandra Geremia
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Cancer Risk ◽  
Sclerosing Cholangitis ◽  
Gamma Glutamyl Transferase ◽  
Transcriptional Alterations ◽  
Inflammatory Bowel ◽  
Bacterial Associations ◽  
Glutamyl Transferase

Background: Primary sclerosing cholangitis (PSC) is a disease of the bile duct and liver. However, patients frequently have co-morbidities including inflammatory bowel disease (IBD) and colorectal cancer. Colorectal cancer risk in patients with PSC-associated ulcerative colitis (PSC/UC) is elevated relative to patients with ulcerative colitis (UC) alone, reasons for which remain obscure. Further, clinical and immunological features, and involved intestinal sites differ between PSC/UC and UC. Understanding the molecular and microbial basis for differences in cancer risk between these two patient groups and how these differ across intestinal sites is important for the development of therapies to prevent colorectal cancer development in at-risk individuals.   Methods: We employed ribonucleic acid sequencing (RNA-seq) analysis of biopsy samples across three intestinal tissue locations (ileum, caecum and rectum) in patients with PSC/UC (n = 8), UC (n = 10) and healthy controls (n = 12) to determine tissue-dependent transcriptional alterations in PSC/UC. We also performed 16S ribosomal RNA (rRNA) amplicon sequencing to determine bacterial associations with PSC/UC and host-microbiome associations. Results: Tissue-defining transcriptional signatures revealed that the ileum was enriched for genes involved in lipid and drug metabolism, the caecum for activated immune cells and the rectum for enteric neurogenesis. Transcriptional alterations relative to healthy control samples were largely shared between patients with PSC/UC or UC although were distinct across tissue locations. Nevertheless, we observed reduced expression of gamma-glutamyl transferase 1 (GGT1) specifically in the ileum and caecum of patients with PSC/UC. Analysis of the bacterial component of the microbiome revealed high inter-individual variability of microbiome composition and little evidence for tissue-dependency. We observed a reduction in Parabacteroides relative abundance in the rectum of patients with PSC/UC. Conclusions: The role of gamma-glutamyl transferase in maintaining the redox environment through the glutathione salvage pathway makes our observed alterations a potential pathway to PSC-associated colorectal cancer.

PP29 ANTILACTOFERRIN ANTIBODIES IN PEDIATRIC PATIENTS: PRIMARY SCLEROSING CHOLANGITIS OR ULCERATIVE COLITIS?

2010 ◽  
Vol 42 ◽  
pp. S341
Author(s):  
F. Bracci ◽  
E. Girolami ◽  
A. Diamanti ◽  
F. Panetta ◽  
L. Giovannelli ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Pediatric Patients

scholarly journals The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Priscila Menezes Ferri ◽  
Ana Cristina Simões e Silva ◽  
Soraya Luiza Campos Silva ◽  
Diego Junior Queiroga de Aquino ◽  
Eleonora Druve Tavares Fagundes ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Clinical Laboratory ◽  
Pediatric Population ◽  
Young Patients ◽  
Cholestatic Liver Disease ◽  
Gamma Glutamyl Transferase ◽  
Immune System Activation ◽  
Glutamyl Transferase

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.

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