Affiliation:
1. Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS , Rome , Italy
2. Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children’s Hospital IRCCS , Rome , Italy
3. Gastroenterology, Digestive Endoscopy and Nutrition Unit, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo ,” Trieste , Italy
4. Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS , Rome , Italy
Abstract
Abstract
Background
Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis.
Methods
By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs).
Results
Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients.
Conclusions
We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.
Funder
Italian Ministry of Health
Publisher
Oxford University Press (OUP)
Subject
Gastroenterology,Immunology and Allergy