RT Journal Article
SR Electronic
T1 Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 899
OP 909
DO 10.1136/gutjnl-2020-323565
VO 71
IS 5
A1 Qiaoyan Liu
A1 Bo Li
A1 Yikang Li
A1 Yiran Wei
A1 Bingyuan Huang
A1 Jubo Liang
A1 Zhengrui You
A1 You Li
A1 Qiwei Qian
A1 Rui Wang
A1 Jun Zhang
A1 Ruiling Chen
A1 Zhuwan Lyu
A1 Yong Chen
A1 Mingxia Shi
A1 Xiao Xiao
A1 Qixia Wang
A1 Qi Miao
A1 Jing-Yuan Fang
A1 Merrill Eric Gershwin
A1 Min Lian
A1 Xiong Ma
A1 Ruqi Tang
YR 2022
UL http://gut.bmj.com/content/71/5/899.abstract
AB Objective Multiple clinical similarities exist between IgG4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC), and while gut dysbiosis has been extensively studied in PSC, the role of the gut microbiota in IgG4-SC remains unknown. Herein, we aimed to evaluate alterations of the gut microbiome and metabolome in IgG4-SC and PSC.Design We performed 16S rRNA gene amplicon sequencing of faecal samples from 135 subjects with IgG4-SC (n=34), PSC (n=37) and healthy controls (n=64). A subset of the samples (31 IgG4-SC, 37 PSC and 45 controls) also underwent untargeted metabolomic profiling.Results Compared with controls, reduced alpha-diversity and shifted microbial community were observed in IgG4-SC and PSC. These changes were accompanied by differences in stool metabolomes. Importantly, despite some common variations in the microbiota composition and metabolic activity, integrative analyses identified distinct host–microbe associations in IgG4-SC and PSC. The disease-associated genera and metabolites tended to associate with the transaminases in IgG4-SC. Notable depletion of Blautia and elevated succinic acid may underlie hepatic inflammation in IgG4-SC. In comparison, potential links between the microbial or metabolic signatures and cholestatic parameters were detected in PSC. Particularly, concordant decrease of Eubacterium and microbiota-derived metabolites, including secondary bile acids, implicated novel host–microbial metabolic pathways involving cholestasis of PSC. Interestingly, the predictive models based on metabolites were more effective in discriminating disease status than those based on microbes.Conclusions Our data reveal that IgG4-SC and PSC possess divergent host–microbe interplays that may be involved in disease pathogenesis. These data emphasise the uniqueness of IgG4-SC.Data are available upon reasonable request. Additional data (beyond those included in the main text and Supplementary Information) are available from the corresponding author upon request.