Table 1.

Alteration of gut microbiome in PBC and PSC patients.

Disease	Material	Patients	IBD controls	HC	Method	Diversity	Key results	Reference
PBC	Stool	79 UDCA treatment-naïve patients with PBC and 37 patients who underwent analysis before and after 6 months of UDCA treatment	0	114	16S rRNA sequencing	Alpha: reduced Beta: shows significant shifts	Increased genus:Enterobacteriaceae, Pseudomonas, Veillonella, Clostridium, Lactobacillus, Haemophilus, Streptococcus, Klebsiella Decreased genus:Oscillospira, Sutterella, Bacteroides, Faecalibacterium	100
PBC	Stool	56 patients with autoimmune liver disease (AILD, including 39 PBC and 17 autoimmune hepatitis)	0	15	Terminal restriction fragment length polymorphism of 16S rDNA	Alpha: no significant change Beta: more clustering in the AILD group than in the HC group	Increased: order Lactobacillales Decreased: genus Clostridium subcluster XIVa	101
PBC	Stool	42 early-stage PBC	0	30	16S rRNA sequencing	Alpha: no significant change Beta: no significant change	Decreased: some potentially beneficial bacteria, such as Acidobacteria, Lachnobacterium sp., Bacteroides eggerthii, and Ruminococcus bromii Increased: some bacterial taxa containing opportunistic pathogens, such as gamma-Proteobacteria, Enterobacteriaceae, Neisseriaceae, Spirochaetaceae, Veillonella, Streptococcus, Klebsiella, Actinobacillus pleuropneumoniae, Anaeroglobus geminatus, Enterobacter asburiae, Haemophilus parainfluenzae, Megasphaera micronuciformis, and Paraprevotella clara	99
PSC	Mucosal biopsies	10 PSC-IBD	10 UC	10	16S rRNA sequencing	Alpha: no significant change Beta: shows significant shifts between different groups	PSC-IBD vs. HC: PSC-IBD in comparison with HC was associated with significant shifts in taxa which included a reduction in family Lachnospiraceae and increase in class Bacilli, genus Pseudomonas and Streptoccocus, and species Haemophilus parainfluenzae PSC-IBD vs. UC: in comparison with UC, PSC-IBD was characterized by a significant difference in 50 taxa, of which 24 were enriched in PSC-IBD. In PSC-IBD, there were reductions in taxa that included phylum Lentisphaerae, class Gammaproteobacteria, families Enterobacteriaceae, Prevotellacae, Paraprevotellacae, and Myxococcales, and genus Streptococcus. PSC-IBD was associated with a significant increase in taxa that included the class Bacilli, genus Staphylococcus, and species Parvimonas sp. and Bacteroides fragilis	105
PSC	Stool (two cohorts, one Norwegian and one German)	136 patients with PSC (58% with IBD)	93	158	Metagenomic shotgun sequencing	Alpha: reduced in PSC patients compared to HC, concomitant IBD had no effect in PSC patients Beta: shows significant shifts between different groups, geography matters	Increased: an enrichment of Clostridium asparagiforme and an unclassified Escherichia species in PSC compared to HC Decreased:Coprococcus catus, Roseburia inulinivorans, Ruminococcus obeum, unclassified Subdoligranulum, Eubacterium rectale, Eubacterium siraeum, Bacteroidales bacterium ph8, Barnesiella intestinihominis, Alistipes shahii, Bacteroides intestinalis Increased prevalence: nine Journal Pre-proof species, including Clostridium clostridioforme, Clostridiales bacterium 1 7 47FAA, Clostridium bolteae, Bifidobacterium bifidum, Clostridium symbiosum, Eggerthella lenta, unclassified Escherichia, unclassified Eggerthella, Clostridium citroniae Decreased prevalence: five species in patients with PSC compared to HC, including Coprobacter fastidiosus, Alistipes senegalensis, Eubacterium ramulus, Eubacterium hallii, Lachnospiraceae bacterium 7 158FAA While several species showed similar patterns in IBD, species like Ruminococcus obeum, Bacteroides intestinalis and several Clostridium species did not differ between IBD and HC	106
PSC	Stool	137 patients with PSC (n = 75 with colitis)	118 UC	133	16S rRNA sequencing	Alpha: shows geographical difference. In the Norwegian cohort, reduced in PSC when compared with HC, but comparable between PSC and UC; In German cohort, comparable between PSC and HC, but increased in PSC when compared with UC Beta: shows significant shifts between PSC and HC or between PSC and UC. PSC is similar to PSC with colitis	PSC vs. HC: bacteria with increased relative abundance in patients with PSC include the genera Veillonella, Streptococcus, Lactobacillus, and Enterococcus and the phylum Proteobacteria, represented by the class Gamma proteobacteria, order Lactobacillales and the class Bacilli Bacteria with decreased relative abundance in patients with PSC include the genera Coprococcus, Holdemanella, Desulfovibrio, Faecalibacterium, and Clostridium IV PSC-IBD vs. PSC: decreased prevalences of Bilophila and Bacteroides in patients with PSC-IBD PSC vs. UC: the phylum Firmicutes was significantly increased in patients with PSC	107
PSC	Stool	7 patients with PSC and IBD	8	8	16S rRNA sequencing	Alpha: reduced in PSC-IBD patients compared to either IBD or HC Beta: not shown	PSC/IBD had a decrease in the relative abundance of Bacteroides compared to HC and IBD	108
PSC	Stool	27 Japanese patients with paediatric-onset PSC	16 patients with UC	23	16S rRNA sequencing	Alpha: reduced in PSC patients when compared to HC, but increased in PSC when compared to UC Beta: shows significant shifts between different groups	PSC vs. HC: the abundance of genus Parabacteroides was significantly decreased; The abundance of Enterococcus was significantly increased PSC vs. UC: the abundance of genus Faecalibacterium, Ruminococcus, and Roseburia was significantly higher in the PSC	109
PSC	Stool	85 (30 PSC, 44 PSC-UC, 11 PSC-CD)	36 UC	263	16S rRNA sequencing	Alpha: reduced in PSC patients when compared to HC, comparable between PSC and UC Beta: shows significant shifts between different groups	Genus Veillonella enriched specifically in PSC	110
PSC	Stool	43 (11 PSC, 32 PSC-IBD)	32 UC	31	16S rRNA sequencing	Alpha: no significant change Beta: shows significant shifts between different groups, PSC-IBD is similar to PSC	Rothia, Enterococcus, Streptococcus, Clostridium, Veillonella, and Haemophilus were markedly overrepresented in PSC regardless of concomitant IBD. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum, and Clostridium colinum were decreased in UC along with genus Roseburia	111
PSC	Mucosal biopsies	11 PSC-IBD	10	9	16S rRNA sequencing	Alpha: not shown Beta: shows significant shifts between different groups	Significant increase in Veillonella, Escherichia, Lachnospiraceae and Megasphera and decrease of Prevotella and Roseburia and a near-absence of Bacteroides in PSC-IBD	112
PSC	Mucosal biopsies	20 (1 PSC, 19 PSC-IBD)	15	9	16S rRNA sequencing	Alpha: no significant change Beta: no significant change	Significant PSC-associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit (OTU) level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders	113
PSC	Stool	66 (18 PSC, 27 PSC-UC, 21 PSC-CD)	13 UC, 30 CD	66	16S rRNA sequencing	Alpha: decreased in PSC especially PSC-IBD Beta: PSC was significantly different from HC, CD, and UC. PSC only was similar to PSC-IBD	Three genera, including Enterococcus, are increased in patients with PSC regardless of concomitant IBD and UDCA treatment	114
PSC	Mucosal biopsies	12 (8 PSC-UC, 4 PSC-CD)	11 UC	9	16S rRNA sequencing	Alpha: decreased in PSC Beta: no significant change	At the genus-like level, the relative abundance of uncultured Clostridiales II was significantly lower in PSC compared with UC and HC	115

Abbreviations: AILD, autoimmune liver disease; CD, Crohn's disease; HC, healthy controls; IBD, inflammatory bowel disease; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; PSC-CD, primary sclerosing cholangitis with concomitant Crohn's disease; PSC-IBD, primary sclerosing cholangitis with concomitant inflammatory bowel disease; PSC-UC, primary sclerosing cholangitis with concomitant ulcerative colitis; UC, ulcerative colitis; UDCA, ursodeoxycholic acid; vs, versus.