Gut microbiome composition in patients with liver cirrhosis with and without hepatic encephalopathy: A systematic review and meta-analysis

Table 2 Basic information included in the study

Ref.	Amplified region/reference databases	Characteristics of gut microbiota/alpha diversity indices
		Age	Gender (male/female)	MELD	Child-Pugh score/class	Etiology	PPI
Wang et al[9], 2023, China	N/A, N/A	Cirrhosis with HE (n = 30): (1) Higher of Burkholderiaceae, Ralstonia, Parabacteroides-distasonis; (2) Phylum: Firmicutes (58.08%), Proteobacteria (18.83%), Bacteroidetes (18.19%), and Actinobacteria (2.5%); (3) Genera: Bacteroides (10.59%), Enterococcus (22.98%), Prevotella (2.21%), Escherichia-Shigella (11.9%), Ruminococcus-gnavus (2.13%), and Streptococcus (5.9%); and (4) Shannon (3.84 ± 2.01), Simpson (0.78 ± 0.19), and Chao 1(231.26 ± 66.41)
		56.13 ± 13.20	19/11	19.67 ± 5.95	Child A: 0, Child B: 9, Child C: 21	HBV (9)/HCV (1)/alcohol (12)/HBV + alcoholic (1)/HCV + alcohol (1)/others (6)	N/A
		Cirrhosis without HE (n = 30): (1) Higher of Aegypius-monachus, Erysipelatoclostridiaceae, and Erysipelotrichales; (2) Phylum: Firmicutes (58.42%), Proteobacteria (15.08%), Bacteroidetes (20.14%), and Actinobacteria (1.6%); (3) Genera: Bacteroides (14.80%), Enterococcus (16.36%), Prevotella (2.55%), Escherichia-Shigella (2.55%), Ruminococcus-gnavus (5.35%), and Streptococcus (3.82%); and (4) Shannon (4.11 ± 1.61), Simpson (0.81 ± 0.18), and Chao 1 (211.16 ± 56.35)
		52.23 ± 9.00	20/10	13.90 ± 6.51	Child A: 9, Child B: 7, Child C: 14	HBV (14)/HCV (1)/alcohol (8)/HBV + alcoholic (3)/HCV + alcohol (1)/others (3)	N/A
Bajaj et al[12], 2012, United State	N/A, RDP	Cirrhosis with HE (n = 17): Leuconostocaceae (2.19 ± 1.08), Clostridiales-Incertae Sedis XIV (0.99 ± 0.21), Ruminococcaceae (5.68 ± 1.42), Lachnospiraceae (9.54 ± 3.72), Enterobacteriaceae (10.02 ± 4.13), Streptococcaceae (4.05 ± 1.98), Fusobacteriaceae (1.36 ± 0.95), Alcaligenaceae (2.61 ± 0.74); N/A
		56 ± 3	16/1	MELD17 ± 6	N/A	Alcohol (10)/others (7)	16
		Cirrhosis without HE (n = 8): Leuconostocacea (1.69 ± 0.95), Clostridiales_Incertae Sedis XIV (1.29 ± 0.35), Fusobacteriaceae (2.75 ± 2.75), Lachnospiraceae (12.08 ± 2.47), and Ruminococcaceae (9.04 ± 2.62); N/A
		55 ± 5	7/1	MELD 12 ± 5	N/A	Alcohol (3)/others (5)	7
Bajaj et al[13], 2015, United State	N/A	Cirrhosis with HE (n = 43): Clostridiales XIV (4.5%), Lachnospiraceae (16%), Ruminococcaceae (7.4%), Fusobacteriaceae (1.0%), Prevotellaceae (5.0%), Enterococcaceae (1.0%), Enterobacteriaceae (1.0%), Erysipelotrichaceae (0.6%), Bacteroidaceae (24.9%), and Streptococcacae (1.9%); N/A
		56 ± 16	34/9	17.2 ± 7.2	9.7 ± 4.4	HCV (20)/alcohol (6)/HCV + alcohol (9)/NASH (7)/others (1)	19
		Cirrhosis without HE (n = 59): ClostridialesXIV (6.6%), Lachnospiraceae (21.3%), Ruminococcaceae (8.7%), Fusobacteriaceae (0%), Prevotellaceae (5.3%), Enterococcaceae (0%), Enterobacteriaceae (3%), Erysipelotrichaceae (1.9%), Bacteroidaceae (24.5%), and Streptococcacae (4.4%); N/A
		54 ± 13	50/9	8.6 ± 2.5	6.2 ± 5.1	HCV (27)/alcohol (14)/HCV + alcohol (7)/NASH (7)/others (4)	21
Bajaj et al[14], 2019, United State	N/A, N/A	Cirrhosis with MHE (n = 122): (1) PHES: Higher of Lactobacillales, Bacilli, and Micrococcaceae; (2) ICT: Higher of Lactobacillales, Enterobacteriales, Bacilli, Enterobacteriaceae, Protebacteria, Gammaprotebacteria, Micrococcaceae, Eubacteriaceae, Streptococcaceae, Actinomycetales; (3) Stroop: Higher of Lactobacillales, Lactocillaceae, Actinobacteria; and (4) Shannon MHE on PHES (1.9 ± 0.7), MHE on ICT (2.0 ± 0.7), and MHE on Stroop 1.9 ± 0.6
		60.1 ± 7.0	122/0	11.3 ± 4.7	N/A	N/A	77
		Cirrhosis without HE (n = 145): (1) PHES: Higher of Clostridiales, Incertae Sedis XI and XIII, Pasteurellales, Pasteurellaceae, Lachnospiraceae, and Clostridia; (2) ICT: Higher of Bacteroidaceae, Bacteroidales, Bacteroidia, Bacteroidetes; (3) Stroop: Higher of Eubacteriaceae, GP1, Telmatobacter, Breoghania, Caulobacterales, Telmatobacter, Acidobacteria, proteobacteria-incertaesedis, Hyphomonadaceae, and Listeriaceae; and (4) Shannon non-MHE on PHES (2.2 ± 0.6), non-MHE on ICT (2.1 ± 0.6), and non-MHE on Stroop (2.1 ± 0.6)
		59.4 ± 9.1	85/60	14.3 ± 7.1	N/A	N/A	54
Bajaj et al[55], 2018, United State	V1-2/RDP	Cirrhosis with prior HE (n = 10): Higher abundance of Erysipelothriceaea, Erysipelotrichia, and Erysipelotrichales; N/A
		N/A	N/A	13.2 ± 3.1	N/A	N/A	N/A
		Cirrhosis without prior HE (n = 14): Higher abundance of Selomonadales and Negativicutes; N/A
		N/A	N/A	7.8 ± 1.7	N/A	N/A	N/A
Sung et al[15], 2019, China	V3-4, N/A	Cirrhosis with HE (n = 62): (1) Firmicutes (41.4%), Bacteroidetes (36.5%), Proteobacteria (15.8%) and Actinobacteria (3.4%); (2) Schlegelella (1.172 ± 2.924), Megasphaera (1.105 ± 1.518), Veillonella (11.007 ± 12.473), Enterococcus (1.369 ± 5.038), Lactobacillus (1.086 ± 3.184), XI (1.603 ± 7.644), Prevotella (1.254 ± 4.101), Sedis (0.401 ± 0.923), Bacteroides (1.780 ± 4.062), and Parabacteroides (0.788 ± 2.946); and (3) Shannon (2.6 ± 0.59) and Chao 1 (146.83 ± 47.35)
		56.7 ± 12.2	49/13	18.5 ± 6	Child A: 0; Child B: 22; Child C: 40	HBV (18)/HCV (19)/alcoholic (36)/others (4)	22
		Cirrhosis without HE (n = 15): (1) Firmicutes (on average 332%), Bacteroidetes (47.2%), Proteobacteria (15.5%), and Actinobacteria (1.4%); (2) Schlegelella (0.029 ± 0.085), Megasphaera (1.031 ± 1.861), Veillonella (6.015 ± 7.01073), Enterococcus (0.02 ± 0.031), Lactobacillus (0.011 ± 0.017), XI (0.039 ± 0.081), Prevotella (0.022 ± 0.084), Sedis (1.788 ± 2.968), Bacteroides (1.607 ± 2.290), and Parabacteroides (1.334 ± 2.269); and (3) Shannon (2.64 ± 0.45) and Chao 1 (194.53 ± 52.93)
		58.1 ± 12.3	12/3	16.8 ± 5.58	Child A: 0; Child B: 8; Child C: 7	HBV (6)/HCV (2)/alcohol (8)/others (0)	4
Bloom et al[8], 2021, Japan	N/A, NCBI	Cirrhosis with HE (prior or current) (n = 33): (1) Higher of Bifidobacteriaceae, Enterococcaceae, Strptoccaceae, Lactobacteriaceae, and Enterobacteriaceae; and (2) Simpson (4.2 ± 2.64)
		57 ± 10	19/14	21 ± 8	N/A	Alcohol (16)/NASH (10)/viral and alcohol (4)/viral (1)/others (2)	28
		Cirrhosis without HE (n = 16): (1) Higher of Lachnospiraceae, Bacteroidaceae, Ruminococcaceae, Veillonellaceae, AKKermansiaceae, and Eubacteriaceae; and (2) Simpson (10.88 ± 9.46)
		59 ± 10	11/5	16 ± 10	N/A	Alcohol (6)/NASH (2)/viral and alcohol (3)/vral (4)/others (1)	11
Saboo et al[56], 2022, United State	V1-2/RDP	Cirrhosis with HE (n = 57): Lower of Lachnospriaceae, Bacteroidaceae, and Ruminococcaceae; N/A
		59.6 ± 6.4	46/11	15.1 ± 7.2	N/A	Alcohol (20)/HCV (22)/NASH (12)/others (3)	28
		Cirrhosis without HE (n = 125): Higher of Lachnospriaceae, Bacteroidaceae, and Ruminococcaceae; N/A
		60.8 ± 7	97/28	9.6 ± 3.8	N/A	Alcohol (54)/HCV (45)/NASH (21)/others (5)	50
Yukawa-Muto et al[10], 2022, Japan	N/A	Decompensated cirrhosis with HE (n = 26): (1) Higher of Streptococcus salivarius, Lactobacillus spp., Bifidobacterium dentium, Lactobacillus mucosae, Lactobacillus fermentum, Veillonella atypica, Veillonella parula, and Lactobacillus rhamnosus; and (2) Shannon (6.47 ± 0.38)
		68.4 (52-85)	15/11	11.7 (6-19)	N/A	HBV (3)/HCV (9)/NASH (7)/alcohol (3)/PBC (3)/AIH (1)	N/A
		Decompensated cirrhosis without HE (n = 27): (1) Lower of Streptococcus salivarius, Lactobacillus spp., Bifidobacterium dentium, Lactobacillus mucosae, Lactobacillus fermentum, Veillonella atypica, Veillonella parula, and Lactobacillus rhamnosus; and (2) Shannon (6.90 ± 0.5)
		67.6 (54-81)	16/11	8.2 (6-12)	N/A	HBV (0)/HCV (26)/NASH (1)/alcohol (0)/PBC (0)/AIH (0)	N/A
Li et al[57], 2022, China	V3-4/RDP	Cirrhosis with HE (n = 33): (1) Higher of Ruminococaceae, Lachnospiraceae, Ruminococcus, Rumi_uncultured, Roseburia, Dialister, Dialister, Coprococcus, Blautia, and Anaerostipes; and (2) Shannon (2.84 ± 0.45) and Chao 1 (221.39 ± 39.36)
		51 (44-58)	19/14	16.84 (13.6, 19.27)	8 (7-11); Child A: 3; Child B: 21; Child C: 9	HBV + HCV (25)/others (8)	N/A
		Cirrhosis without HE (n = 73): (1) Lower of Ruminococaceae, Lachnospiraceae, Ruminococcus, Rumi_uncultured, Roseburia, Dialister, Dialister, Coprococcus, Blautia, and Anaerostipes; and (2) Shannon (3.04 ± 0.39) and Chao 1 (244.24 ± 58.72)
		52 (45-58)	46/27	14.34 (12.15, 16.47)	7 (6-8); Child A: 34; Child B: 35; Child C: 4	HBV + HCV (50)/others (23)	N/A
Hua et al[58], 2022, China	N/A	Cirrhosis with HE (n = 5): (1) Higher of Pasteurellales, Pasteurellaceae, Haemophilus, and Selenomonas; (2) Higher of Veillonella (4.12 ± 6.09), Pasteurellales (2.39 ± 4.04), Pasteurellaceae (2.39 ± 4.04), Haemophilus (2.34 ± 3.96), Selenomonas (0.016 ± 0.04), Lachnospiraceae (11.48 ± 6.53), Coprococcus (0.311 ± 0.292), and Dorea (0.855 ± 0.716); and (3) N/A
		60.11 ± 9.54	4/1	N/A	N/A	HBV (5)	N/A
		Cirrhosis without HE (n = 15): (1) Higher of Veillonella; (2) Higher of Veillonella (4.40 ± 6.13), Blautia (1.36 ± 1.88), Turicibacterales (0.012 ± 0.039), Turicibacter (0.012 ± 0.039), Turicibacteraceae (0.012 ± 0.039), Adlercreutzia (0.053 ± 0.014), Holdemania (0.009 ± 0.016), and Coprococcus (0.305 ± 0.43); (3) Lachnospiraceae (9.08 ± 6.38); and (4) N/A
		61.73 ± 13.55	11/4	N/A	N/A	HBV (15)	N/A
Bajaj et al[59], 2022, United State	V1-2/RDP	Cirrhosis with MHE (n = 180): Higher of Pediococcus, Lacticaseibacillus, Pseudomonas, Doudenibacillus, Lactobacillus, Enterococcus, Escherichia-Shigella, Limosilactobacillus, Klebsiella, Sutterella, Megamonas, Veillonella, Absiella, and Prevotellamassila; N/A
		N/A	N/A	N/A	N/A	N/A	N/A
		Cirrhosis without MHE (n = 141): Higher of Enterobacter, Weissella, Anaerobutyrium, Romboutsia, and Citrobacter; N/A
		N/A	N/A	N/A	N/A	N/A	N/A
Yu et al[11], 2021, China	N/A, NCBI	Cirrhosis with HE (n = 5): (1) Higher of Bacteroidetes and Proteobacteria; (2) Lower of Firmicutes, Candidatus Saccharibacteria, and the Verrucomicrobia phyla; and (3) Shannon (1.78 ± 0.52), Simpson (0.71 ± 0.15), and Chao 1 (48.42 ± 17.78)
		58.2 ± 7.04	3/2	N/A	N/A	N/A	N/A
		Cirrhosis without HE (n = 16): (1) Lower of Bacteroidetes and Proteobacteria; (2) Higher of Firmicutes, Candidatus Saccharibacteria, and the Verrucomicrobia phyla; and (3) Shannon (2.23 ± 0.4), Simpson (0.82 ± 0.07), and Chao 1 (68.14 ± 20.05)
		55.33 ± 5.86	10/6	N/A	N/A	N/A	N/A
Bajaj et al[60], 2020, United State	N/A, MYSQL	Cirrhosis with HE 16S rRNA (n = 29): (1) Bacteroidaceae (35%), Prevotellaceae (0%), Lactobacillaceae (1%), Lachnospiraceae (11.3%), Ruminococcaceae (4.4%), Streptococcaceae (1%), Veillonellaceae (0%), and Enterobacteriaceae (1%); and (2) Shannon (1.49 ± 0.37)
		58.8 ± 11.7	20/9	14.8 ± 7	N/A	N/A	28%
		Cirrhosis without HE (n = 51): (1) Bacteroidaceae (33%), Prevotellaceae (0%), Lactobacillaceae (1%), Lachnospiraceae (26%), Ruminococcaceae (10%), Streptococcaceae (0.1%), Veillonellaceae (0%), and Enterobacteriaceae (0%); and (2) Shannon (1.6 ± 0.4)
		57.9 ± 7.4	36/15	9.5 ± 3.4	N/A	N/A	18%
Ahluwalia et al[16], 2016, United State	N/A	Cirrhosis with prior HE (n = 85): (1) Phylum: Firmicutes (24 ± 20), Bacteroidetes (24 ± 26), Proteobacteria (7 ± 15); (2) Family: Bacteroidetes-Bacteroidaceae (18.2 ± 25.2), Bacteroidetes_Porphyromonadaceae (3.9 ± 7.7), Bacteroidetes-Prevotellaceae (2.9 ± 8), Bacteroidetes-Rikenelleaceae (0 ± 2.4), Firmicutes_Lactobacillaceae (4 ± 9.5), Firmicutes-Enterococcaceae (3.6 ± 10.9), Firmicutes-Clostridiales XIV (1.4 ± 3.5), Firmicutes-Lachnospiraceae (6.3 ± 11), Firmicutes-Ruminococcaceae (3.0 ± 5.4), Firmicutes-Veillonellaceae (2. 0 ± 4.8), and Proteobacteria_Enterobacteriaceae (5.5 ± 14.8); and (3) N/A
		56.2 ± 13.5	16/69	15.5 ± 5.2	N/A	HCV (27)/alcohol (16)/HCV + alcohol (20)/NASH (12)/others (10)	N/A
		Cirrhosis without prior HE (n = 62): (1) Phylum: Firmicutes (28 ± 19), Bacteroidetes (33 ± 30), and Proteobacteria (3 ± 6); (2) Family: Bacteroidetes-Bacteroidaceae (22.2 ± 24), Bacteroidetes-Porphyromonadaceae (2.1 ± 5.2), Bacteroidetes-Prevotellaceae (4.5 ± 13.5), Bacteroidetes-Rikenelleaceae (2.0 ± 5.5), Firmicutes-Lactobacillaceae (2.0 ± 8.5), Firmicutes-Enterococcaceae (1.1 ± 6.7), Firmicutes-Clostridiales XIV (3.2 ± 4.7), Firmicutes-Lachnospiraceae (10.5 ± 8.4), Firmicutes-Ruminococcaceae (5.5 ± 6.2), Firmicutes-Veillonellaceae (1.7 ± 2.9), and Proteobacteria-Enterobacteriaceae (2.4 ± 5.9); and (3) N/A
		54.2 ± 11.6	46/16	11.0 ± 4.2	N/A	HCV (21)/alcohol (15)/HCV + alcohol (3)/NASH (15)/others (8)	N/A
Zhang et al[17], 2013, China	N/A	Cirrhosis with MHE (n = 26): Higher of S. salivarius; Chao 1 (276 ± 104)
		53 ± 12	13/13	N/A	Child A: 3; Child B: 16; Child C: 7	AIH (1)/HBV (13)/PBC (7)/PSC (0)/alcohol (5)	N/A
		Cirrhosis without MHE (n = 25): Lower of S. salivarius; Chao 1 (250 ± 139)
		59 ± 11	16/9	N/A	Child A: 12; Child B: 11; Child C: 2	AIH (2)/HBV (12)/PBC (3)/PSC (1)/alcohol (7)	N/A
Bajaj et al[61], 2012, United State	N/A	Cirrhosis with HE (n = 19): Incertae Sedis XIV_Blautia (1.6%), Incertae Sedis XIV_other (1.4%), and Fusobacteriaceae_other (1.1%); N/A
		N/A	N/A	N/A	N/A	N/A	N/A
		Cirrhosis without HE (n = 17): Leuconostocaceae_Leuconostoc (1.0%), Bacteroidales incertae sedis other (1.0%), and Alcaligenaceae other (0.8%); N/A
		N/A	N/A	N/A	N/A	N/A	N/A

MELD: Model for end-stage liver disease; RDP: Ribosomal database project; HE: Hepatic encephalopathy; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PPI: Proton pump inhibitor; AIH: Autoimmune hepatitis; NASH: Nonalcoholic steatohepatitis; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; ICT: Inhibitory control test, MHE: Minimal hepatic encephalopathy; NCBI; National Center for Biotechnology Information; PHES: Psychometric hepatic encephalopathy score; N/A: Not applicable.