Microbiome-immune interactions in autoimmune liver diseases

Table 6 Gut microbiota-targeted therapy in the treatment of primary sclerosing cholangitis and its experimental models

Ref.	Model/patients	Sequencing method	Intervention	Taxa increased in gut microbiota after the treatment	Taxa decreased in gut microbiota after the treatment	Changes in gut after the treatment	Changes in immune system after the treatment	Changes in liver after the treatment	Other notes
Experimental models of primary sclerosing cholangitis
D’Onofrio et al[162]	DDC-diet induced mouse model	16S rRNA	Indole-3-carboxaldehyde-loaded enteric microparticles	Lactobacillus reuteri	Escherichia coli, Klebsiella pneumonia	Increased ZO-1 expression and improved intestinal permeability	Reduced serum IL-6, IL-17A, INF-γ, TNF-α, decreased hepatic CD11b+, F4/80+ cells	Decreased serum ALT, total bilirubin
Jiang et al[164]	DDC-diet induced mouse model	16S rRNA	Prevotella copri treatment	Prevotella copri, Muribaculaceae, Lactobacillus, Turicibacter, Bifidobacterium, Clostridium sensu stricto, Odoribacter, Alistipes	Staphylococcus, Akkermansia			Decreased serum ALT, AST, ALP, total bilirubin, reduced collagen-1a and TIMP1 hepatic expression	Activated FXR signalling pathway
Han et al[161]	DDC-diet induced mouse model	16S rRNA	Pediococcus pentosaceus Li05 treatment	Bacteroidaceae, Ruminococcaceae, Sutterellaceae, Rhodocyclaceae, Bacteroides, Ruminococcus, Pediococcus, Tuzzerella	Erysipelotrichaceae, Eggerthellaceae, Anaeromyxobacteraceae, Comamonadaceae, Faecalibaculums, Turicibacter, Enterorhabdus, Lactobacillus	Restored expression of ZO-1, occludin, claudin1, and MUC2	Decreased hepatic expression of IL-1β, IL-6, TNF-α, decreased serum IL-1β, IL-2, IL-6, INF-γ	Decreased serum ALT, AST, ALP, total and direct bilirubin, total BAs; reduced hepatic necrosis and infiltration	Increased FXR and FGF15 ileal expression, increased fecal BAs and SCFAs
Xiao et al[163]	C57BL/6J mice	16S rRNA	Oral vancomycin for 3 weeks + Clostridium scindens for 3 days					Decreased serum ALT, AST, decreased hepatic collagen synthesis and deposition, ACTA2, Col1a1 and TGF-β expression	Decreased primary/secondary bile acid ratio
Patients with primary sclerosing cholangitis
Philips et al[170]	38 years old male patient with PSC	16S rRNA	FMT	Bacteroides, Megamonas, Bifidobacterium	Proteobacteria, Clostridium, Veillonella, Fecalibacterium, Oscillopsira, Lachnospira			Decreased serum ALT, AST, ALP, GGT, total bilirubin	Decreased total BAs
Allegretti et al[171]	PSC + IBD, n = 10	16S rRNA	FMT	Odoribacter, Alistipes, Erysipelotrichaceae incertae sedis, Clostridia	Negativicutes, Verrucomicrobiae			Decreased ALP	BAs profile did not change
Quraishi et al[169]	PSC-IBD, n = 15	16S rRNA	Oral vancomycin for 4 weeks	Fusobacteria, Verrucomicrobia, Fusobacterium nucleatum, Enterobacter hormaechei, Escherichia coli, Veillonella, Klebsiella, Akkermansia muciniphila, Roseburia hominis, Prevotella buccae, Lachnospiraceae bacterium, Blautia hansenii, Bacteroides thetaiotaomicron	Faecalibacterium prausnitzii, Anaerostipes hadrus, Bifidobacterium longum, Clostridium, Ruminococcus, Lachnospira, Roseburia	Reduction in fecal calprotectin and mucosal inflammation		Decreased serum ALT, ALP, total bilirubin	Decreased secondary BAs, increased primary BAs, reduced fecal SCFAs

DDC: 3,5-diethoxycarbonyl-1,4-dihydrocollidine; IBD: Inflammatory bowel disease; PSC: Primary sclerosing cholangitis; FMT: Fecal microbiota transplantation; ZO-1: Zonula occludens-1; IL: Interleukin; TGF: Transforming growth factor; IFN: Interferon; TNF: Tumor necrosis factor; CD: Cluster of differentiation; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transpeptidase; ALP: Alkaline phosphatase; FXR: Farnesoid X receptor; FGF: Fibroblast growth factor; SCFAs: Short-chain fatty acids; BAs: Bile acids.