Microbiome-immune interactions in autoimmune liver diseases

Table 1 Gut dysbiosis in experimental models of autoimmune hepatitis and in patients with this disease

Ref.	Model/patients	Sample	Sequencing method	Decreased gut microbiota taxa	Increased gut microbiota taxa	Correlations
Experimental models of autoimmune hepatitis
Wang et al[34]	MRL+/+ mice treated with 0.5 mg/mL trichloroethene	Feces	16S rRNA	Lactobacillus, Bifidobacterium, Rikenellaceae	Akkermansiaceae, Lachospiraceae	Dysbiosis associated with increased gut permeability
Centa et al[35]	Traf6ΔTEC mice	Feces	16S rRNA	Ruminococcaceae, Clostridiales	Sutterella, Parabacteroides distasonis, Bacteroides acidifaciens, Parabacteroides-like S24-7	Dysbiosis associated with increased Foxp3+ T cells and hepatic inflammation
Wang et al[36]	ConA-induced hepatitis in GSDMD-/- mice	Feces	16S rRNA	Lactobacillus, Roseburia	Allobaculum, Dubosiella	Lactobacillus negatively correlated with AST, hepatic expression of IL-17, serum IFN-γ, TNF-α, IL-17A and positive correlation with tight junction proteins expression; Allobaculum and Dubosiella positively correlated with ALT, AST, hepatic pathological score, serum IFN-γ, TNF-α, IL-17A and negatively correlated with tight junction protein expression
Kang et al[37]	S100/complete Freund’s adjuvant-induced AIH mouse model	Feces	16S rRNA	Ruminococcaceae, Clostridia UCG-014, Rikenella, Dubosiella, Alistipes, Bifidobacterium	Lactobacillaceae, Enterobacteriaceae, Escherichia-Shigella Alloprevotella, Proteobacteria, Bacteroides	Bacteroides vulgatus, Alloprevotella, Lactobacillus murinus, and Prevotellaceae UCG-001 positively correlated with bacterial translocation, inflammatory cytokine expression and negatively correlated with tight junction proteins expression
Lin et al[38]	S100-induced mice model in Pigr-/- mice	Feces	qRT-PCR	Akkermansia	Lactobacillus, Anaeromassilibacillus, Oscillospiraceae	Depletion of Pigr increased intestinal dysbiosis and permeability, but this effect was reduced after antibiotics treatment
Patients with autoimmune hepatitis
Lin et al[39]	Naive AIH, n = 24; HCs, n = 8	Feces	16S rDNA quantitative PCR	Bifidobacterium, Lactobacillus		Association of serum LPS, decreased expression of ZO-1 and occludin with advanced stages of the disease
Abe et al[40]	AIH, n = 17; PBC, n = 39; HCs, n = 15	Saliva	16S rRNA	Streptococcus, Fusobacterium	Veillonella, Neisseria	Veillonella positively correlated with the salivary levels of IL-1β, IL-6, IL-8, IL-12p70 and IgA
		Feces	16S rDNA	Clostridium cluster XIVa	Lactobacillales
Lou et al[41]	Naive AIH, n = 37; HCs, n = 78	Feces	16S rRNA	Pseudobutyrivibrio, Blautia, Lachnospira, Alistipes, Phascolarctobacterium, Erysipelotrichaceae incertae sedis, Ruminococcaceae incertae sedis	Veillonella, Faecalibacterium, Klebsiella, Gemella, Akkermansia, Lactobacillus	Veillonella, Lactobacillus, Megasphaera, Klebsiella, Faecalibacterium correlated with AST, ALT, GGT and total bilirubin; Akkermansia correlated with AST and ALT
Liwinski et al[33]	AIH, n = 72; HCs, n = 95; PBC, n = 99; UC, n = 81	Feces	16S rRNA	Faecalibacterium, Bifidobacterium	Streptococcus, Veillonella, Lactobacillus	Decreased Bifidobacterium associated with an increase of serum IgG; Veillonella abundance associated with ALT
Elsherbiny et al[42]	Naive AIH, n = 15; HCs, n = 10	Feces	16S rRNA	Prevotella, Parabacteroides, Dilaster	Faecalibacterium, Blautia, Streptococcus, Haemophilus, Bacteroides, Veillonella, Eubacterium, Lachnospiraceae, Butyricicoccus
Wei et al[10]	Naive AIH, n = 91; HCs, n = 98	Feces	16S rRNA	Clostridiales, RF39, Ruminococcaceae, Rikenellaceae, Oscillospira, Parabacteroides, Coprococcus	Veillonella, Klebsiella, Streptococcus, Lactobacillus	Veillonella positively correlated with AST and hepatic inflammation
Liang et al[43]	Naive AIH, n = 32; NAFLD, n = 20; HCs, n = 20	Feces	qRT-PCR, 16S rRNA	Bifidobacterium, Lactobacillus, Bacteroides, Clostridium leptum	Escherichia coli
Zhang et al[44]	Naive AIH, n = 68; HCs, n = 15	Feces	16S rRNA	Lactobacillus, Ruminiclostridium	Bacteroides, Prevotellaceae UCG-001

ConA: Concanavalin A; GSDMD: Gasdermin D; Pigr: Polymeric immunoglobulin receptor; AIH: Autoimmune hepatitis; HC: Healthy controls; qRT-PCR: Quantitative real-time polymerase chain reaction; PBC: Primary biliary cholangitis; NAFLD: Non-alcoholic fatty liver disease; UC: Ulcerative colitis; IL: Interleukin; IFN: Interferon; TNF: Tumor necrosis factor; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; LPS: Lipopolysaccharide; ZO-1: Zonula occludens-1; IgA: Immunoglobulin A; IgG: Immunoglobulin G; GGT: Gamma-glutamyl transpeptidase.