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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis
Lukas Bajer, Miloslav Kverka, Martin Kostovcik, Peter Macinga, Jiri Dvorak, Zuzana Stehlikova, Jan Brezina, Pavel Wohl, Julius Spicak, Pavel Drastich
Lukas Bajer, Peter Macinga, Jan Brezina, Pavel Wohl, Julius Spicak, Pavel Drastich, Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, 14021 Prague, Czech Republic
Miloslav Kverka, Jiri Dvorak, Zuzana Stehlikova, Institute of Microbiology, the Czech Academy of Sciences, 14220 Prague, Czech Republic
Miloslav Kverka, Institute of Experimental Medicine, the Czech Academy of Sciences, 14220 Prague, Czech Republic
Martin Kostovcik, Department of Genetics and Microbiology, Faculty of Science, Charles University, 12844 Prague, Czech Republic
Martin Kostovcik, BIOCEV, Institute of Microbiology, the Czech Academy of Sciences, 25242 Vestec, Czech Republic
Author contributions: Bajer L, Kverka M and Drastich P wrote the paper; Bajer L, Dvorak J and Stehlikova Z performed the experiments; Kverka M designed the research; Bajer L and Kostovcik M analyzed the data; Kostovcik M reviewed statistical methods; Macinga P and Brezina J recruited patients; Wohl P assessed clinical data; Spicak J and Drastich P supervised the research and revised the report; all authors contributed to this manuscript.
Supported by Ministry of Health of the Czech Republic, No. 15-28064A.
Institutional review board statement: This study was approved by The Ethics Committee with multicenter competence of the Institute for Clinical and Experimental Medicine and Thomayer Hospital.
Informed consent statement: All patients and healthy controls signed the informed consent form at the time of sample collection.
Conflict-of-interest statement: The authors declare that there are no competing interests regarding the publication of this paper.
Data sharing statement: Data sharing agreement was not included in the informed consent signed by the participants. The dataset supporting the conclusions of this article is available in the Short Read Archive repository. http://www.ncbi.nlm.nih.gov/bioproject/368966.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pavel Drastich, MD, PhD, Associate Professor, Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 14021 Prague, Czech Republic.
pavel.drastich@ikem.cz
Telephone: +420-2-61362266 Fax: +420-2-61362615
Received: January 26, 2017
Peer-review started: February 3, 2017
First decision: March 16, 2017
Revised: April 10, 2017
Accepted: June 1, 2017
Article in press: June 1, 2017
Published online: July 7, 2017
Processing time: 162 Days and 10.9 Hours
AIM
To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC).
METHODS
Stool 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.
RESULTS
Microbial 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.
CONCLUSION
PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).
Core tip: This study demonstrates specific microbial patterns associated with PSC and/or concomitant inflammatory bowel disease (PSC-IBD). Several bacterial taxa convincingly distinguish PSC-IBD from ulcerative colitis. Gut microbiota composition also differs in patients with PSC overlap with autoimmune hepatitis. Disease-specific microbial features traceable down to the species level may lead to establishing suitable biomarkers or outlining new research directions in the field of PSC and IBD pathogenesis.
