Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis

Abstract

ObjectiveMultiple 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.DesignWe 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.ResultsCompared 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.ConclusionsOur 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.

A novel serum metabolomic panel distinguishes IgG4‐related sclerosing cholangitis from primary sclerosing cholangitis

“…The faecal microbiome and metabolome have been compared between IgG4-SC and PSC. 20 Interestingly, whilst many microbial and faecal metabolic features were shared between PSC and IgG4-SC compared to HCs, IgG4-SC showed an increase in immune-related metabolites as determined by mass spectrometry. For example proinflammatory mediators such as arachidonic acid and sphinganine, the precursor of ceramide, were uniquely elevated in the faeces of patients with IgG4-SC compared to patients with PSC or HCs.…”

“…Accordingly, we used NMR metabolomics An integrated analysis of the faecal metabolome and microbiome in PSC and IgG4-SC revealed distinct disease profiles. 20 Despite a high level of microbe-metabolite correlation, faecal metabolites performed better at predicting disease status than microbial taxa. In contrast, the study presented here, is the first to apply blood-based NMR metabolomics to directly compare PSC with IgG4-SC.…”

Gut Microbiome Signatures in the Progression of Hepatitis B Virus-Induced Liver Disease

“…From CHB to LC, Oscillibacter, Oscillospiraceae_UCG-005 , and Prevotella were depleted. The decrease of gut Oscillibacte r and Prevotella was observed in severe alcoholic hepatitis and amyotrophic lateral sclerosis (Fang et al, 2016 ; Kim et al, 2021 ), while Oscillospiraceae_UCG-005 was decrease inprimary sclerosing cholangitis (Liu et al, 2021 ). From LC to HCC, Ruminococcaceae, Clostridia_UCG-014, Oscillospiraceae_UCG-002 and Coprococcus were decreased.…”

Altered Fecal Metabolomics and Potential Biomarkers of Psoriatic Arthritis Differing From Rheumatoid Arthritis

“…Furthermore, in intestinal macrophages, G protein-coupled bile acid receptor 1 (GPBAR1) and Farnesoid-X-receptor (FXR) are highly expressed, which also occurs in innate immunity such as dendritic cells and natural killer cells ( 16 , 35 ). Additionally, secondary bile acids, namely, lithocholic acid and deoxycholic acid, have been reported to protect the intestinal barrier ( 38 , 39 ). Taken together, the data reported in our study indicated that alteration of bile acid homeostasis may be related to the occurrence and development of PsA.…”