Microbiome-immune interactions in autoimmune liver diseases

Table 3 Gut dysbiosis in experimental models of primary biliary cholangitis and in patients with this disease

Ref.	Model/patients	Sample	Sequencing method	Decreased gut microbiota taxa	Increased gut microbiota taxa	Correlations
Experimental models of primary biliary cholangitis
Ma et al[89]	TLR2-deficient dnTGF-βR II mice	Feces	16S rRNA	S24-7, Ruminococcaceae, Rikenellaceae, Porphyromonadaceae	Lachnospiraceae, Bacteroidaceae	Treatment with antibiotics associated with significantly reduced hepatic mononuclear cells
Wang et al[90]	2-OA-OVA-induced murine cholangitis	Feces	16S rRNA		Clostridiaceae, Lachnospiraceae, Ruminococcaceae	TLR2 (receptor for microbial antigens) activation associated with cholangiocyte apoptosis
Liu et al[91]	DDC-diet mouse model	Liver	16S rRNA		Ligilactobacillus murinus, Lactococcus garvieae	Lactococcus garvieae aggravates DDC-induced cholangitis and was only found in PBC patients but not HCs
Patients with primary biliary cholangitis
Lv et al[92]	PBC, n = 42; HCs, n = 30	Feces	16S rRNA	Acidobacteria, Lachnobacterium, Bacteroides eggerthii, Ruminococcus bromii	γ-Proteobacteria, Enterobacteriaceae, Neisseriaceae, Spirochaetaceae, Veillonella, Streptococcus, Klebsiella, Actinobacillus pleuropneumoniae, Anaeroglobus geminatus, Enterobacter asburiae, Haemophilus parainfluenzae, Megasphaera micronuciformis and Paraprevotella clara	Fusicatenibacter and Roseburia faecis negatively associated with IgG; Megamonas negatively associated with ALT; Enterobacteriaceae positively correlated with ALT and direct bilirubin; Catenibacterium positively correlated with IL-16; Parasutterella secunda positively associated with GGT; Prevotella positively associated with IL-8
Tang et al[11]	PBC, n = 60; HCs, n = 80	Feces	16S rRNA	Sutterella, Oscillospira, Faecalibacterium, Bacteroides	Haemophilus, Veillonella, Clostridium, Lactobacillus, Streptococcus, Pseudomonas, Klebsiella, an unknown genus in the family of Enterobacteriaceae	Faecalibacterium negatively correlated with gp210; Lactobacillus positive; correlated with conjugated bilirubin; Klebsiella positively correlated with GGT, total and conjugated bilirubin
Abe et al[40]	Naive AIH, n = 17; naive PBC, n = 39; HCs, n = 15	Saliva	16S rRNA	Fusobacterium	Veillonella, Eubacterium	Veillonella positively correlated with the levels of salivary IL-1β, IL-8 and IgA
		Feces		Clostridium cluster XIVa	Lactobacillales	Fecal Lactobacillales positively correlated with Veillonella in saliva
Furukawa et al[93]	PBC, n = 76; HCs, n = 23	Feces	16S rRNA	Clostridiales, Lachnospiraceae, Ruminococcaceae, Faecalibacterium	Bifidobacterium, Streptococcus, Lactobacillus, Enterococcus, Prevotella	Faecalibacterium abundance positively correlated with UDCA response
Lammert et al[94]	PBC with non-advanced fibrosis, n = 15; PBC with advanced fibrosis, n = 8	Feces	16S rRNA	Weissella, Ruminococcaceae UCG-005, Ruminococcaceae UCG-004, Ruminococcaceae NK4A214, Christensenellaceae R-7, Lachnospiraceae in advanced fibrosis group	Veillonella, Ruminococcaceae UCG-010 in advanced fibrosis group	Collinsella positively correlated with total SCFAs within non-advanced fibrosis; Lachnospiraceae and Collinsella positively correlated with fecal acetate within non-advanced fibrosis; fecal acetate and SCFAs were higher in advanced fibrosis
Kitahata et al[95]	PBC, n = 34; HCs, n = 21	Small intestinal mucosa	16S rRNA	Leptotrichiaceae, Burkholderiaceae, Comamonadaceae	Sphingomonadaceae, Pseudomonadaceae, Methylobacteriaceae, Moraxellaceae	Sphingomonadaceae associated with chronic nonsuppurative destructive cholangitis
Huang et al[96]	PBC FHRAC-positive, n = 25; PBC FHRAC-negative, n = 18	Feces	16S rRNA	Lachnospiraceae incertae sedis, Anaerostipes, Clostridium XlVb, Ruminococcus, Faecalibacterium, Fusicatenibacter in FHRAC-positive patients	Campylobacter, Lachnospira, Desulfovibrio, Klebsiella, Barnesiella, Lactobacillus, Romboutsia, Turicibacter, Acidaminococcus in FHRAC-positive patients	Lachnospiraceae incertae sedis and Veillonella associated with FHRAC
Zhou et al[8]	Naive PBC, n = 25, HCs, n = 25	Feces	16S rRNA	Faecalibacterium, Ruminococcaceae, Sutterellaceae, Oscillospiraceae, Parasutterella, Clostridia, Coprococcus, Christensenellaceae	Acidimicrobiia, Yersiniaceae, Serratia	Oscillospiraceae negatively correlated with anti-gp210; Serratia and Yersiniaceae positively related to the IgG level
Shi et al[97]	PBC ALBI grade 1, n = 36; PBC ALBI grade 2-3, n = 39	Feces	16S rRNA	Clostridia, Lachnospira in ALBI 2-3 patients	Bacilli, Lactobacillales, Streptococcus in ALBI 2-3 patients

TLR: Toll like receptor; 2-OA-OVA: Ovalbumin conjugated with 2-octynoic acid; dnTGF-βR: Dominant negative form of transforming growth factor β receptor; DDC: 3,5-diethoxycarbonyl-1,4-dihydrocollidine; PBC: Primary biliary cholangitis; AIH: Autoimmune hepatitis; HC: Healthy controls; FHRAC: Patients with a combination of five HLA-DRB1 high-risk alleles; ALBI: Albumin-bilirubin; IgG: Immunoglobulin G; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transpeptidase; SCFAs: Short-chain fatty acids; IL: Interleukin; UDCA: Ursodeoxycholic acid.