Gut microbiota in non-alcoholic fatty liver disease: Pathophysiology, diagnosis, and therapeutics

Table 1 Gut microbiota alterations associated with non-alcoholic fatty liver disease

Number of participants	Microbiota alterations	Ref.
NASH (n = 65), HC (n = 76)	Increased Collinsella, decreased Ruminococcaceae in NASH	[61]
NAFLD (n = 87), obesity without NAFLD (n = 37)	High abundance of Prevotella copri in severe fibrosis	[62]
Obese youth with NAFLD (n = 44), without NAFLD (n = 29)	Higher Firmicutes-to-Bacteroidetes ratio and lower abundance of Bacteroidetes, Prevotella, Gemmiger, and Oscillospira in NAFLD	[63]
NAFLD (n = 43), HC (n = 83)	Reduction in Firmicutes and Clostridia, increase in Bacteroidetes and Bacteroidia, decrease in Lachnospiraceae, Ruminococcaceae, Lactobacillaceae, and Peptostreptococcaceae in NAFLD	[64]
HS (n = 56), HC (n = 49)	Fewer Lachnospiraceae and Ruminococcaceae, enrichment of Acidaminococcus, Escherichia spp., Bacteroides spp.	[66]
Stage 0-2 NAFLD-related fibrosis (n = 72), stage 3 or 4 NAFLD-related fibrosis (n = 14)	Eubacterium rectale and Bacteroides vulgatus abundant in mild/moderate NAFLD, Bacteroides vulgatus and Escherichia coli most abundant in advanced fibrosis. Ruminococcus obeum CAG:39, Ruminococcus obeum, and Eubacterium rectale significantly lower in advanced fibrosis	[67]
NAFLD (n =25), HC (n = 22)	Escherichia_Shigella, Lachnospiraceae_Incertae_Sedis, and Blautia more abundant, Prevotella decreased in NAFLD. Higher abundance of genus Blautia and the corresponding Lachnospiraceae family in NASH. Higher abundance of Escherichia_Shigella and the corresponding Enterobacteriaceae family in fibrosis	[60]
NASH (n = 46), HC (n = 38)	Significant reduction in Akkermansia muciniphila and increase in Enterobacteriaceae in NASH	[74]
Total (n = 1148), NAFLD (n = 205)	Significant reduction in family Ruminococcaceae and the genus Faecalibacterium in NAFLD	[75]
NAFLD-cirrhosis (n = 27), non-NAFLD control (n = 54)	Enrichment in Negativicutes, reduction in Clostridia	[68]
SS (n = 11), NASH (n = 22), HC (n = 17)	Lower percentage of Bacteroidetes (Bacteroidetes to total bacteria counts) in NASH than SS and HC	[69]
Severe steatosis (n = 36), fibrosis (n = 13)	Significantly reduction in relative abundance of fecal Clostridium sensu stricto in liver fibrosis	[70]
NAFLD (n = 60), chronic viral hepatitis (n = 32), HC (n = 50)	Escherichia coli predominant bacterium in NAFLD	[79]
NAFLD (n = 29), HC (n = 25)	Expansion of Escherichia_Shigella in NAFLD	[81]
NAFLD (n = 57)	Bacteroides abundance significantly increased, Prevotella abundance decreased in NASH and F ≥ 2. Ruminococcus abundance significantly higher in F ≥ 2 patients	[84]
Total (n = 1355), steatosis (n = 472)	Coprococcus, Ruminococcus gnavus increased in steatosis	[85]
SS (n = 15), NASH (n = 24), HC (n = 28)	Less abundance of Bacteroidetes and Firmicutes, more abundance of Lactobacillus and Lactobacillaceae in NAFLD compared to HC. Lower abundance of Ruminococcus, Faecalibacterium prausnitzii and Coprococcus in both NASH and SS patients compared to HC	[86]
NAFLD (n = 13), obese no NAFLD (n = 11), HC (n = 26)	More abundance of Gammaproteobacteria and Prevotella in NAFLD	[88]
NASH (n = 16), HC (n = 8)	More abundance of Bacteroidetes (Bacteroides and Prevotella genus) in NASH	[89]
MAFLD (n = 32), HC (n = 30)	Increased abundance of Prevotella, Bacteroides, and Escherichia-Shigella in MAFLD	[90]
Obese with NAFLD (n = 36), obese without NAFLD (n = 17), HC (n = 20)	Decreased abundance of Blautia, Alkaliphilus, Flavobacterium, and Akkermansia in obese subjects, with or without NAFLD, and increased abundance of Streptococcus in NAFLD	[92]
NAFLD (n = 90), HC (n = 90)	Increase Slackia, Dorea formicigenerans Methanobrevibacter and Phascolarctobacterium in NAFLD	[93]
MAFLD (n = 81), HC (n = 25)	Enrichment of Dorea, Lactobacillus and Megasphaera in MAFLD	[94]
Mild NAFLD (n = 33), moderate NAFLD (n = 20), severe NAFLD (n = 30), HC (n = 21)	Enrichment of Faecalibacterium, Subdoligranulum, Haemophilus, and Roseburia in NAFLD	[97]
NAFL (n = 14), NASH (n = 18), HC (n = 27)	Higher abundance of Fusobacteria and Fusobacteriaceae in NASH compared to NAFL and HCs	[98]
NAFLD-related cirrhosis and HCC (n = 21), NAFLD-related cirrhosis without HCC (n = 20), HC (n = 20)	Higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia in cirrhosis. Higher abundance of Bacteroides and Ruminococcaceae, reduction in Bifidobacterium in HCC	[8]
NAFLD (n = 98), first-degree relatives (n = 105)	Enrichment of Streptococcus and Megasphaera in NAFLD-cirrhosis	[99]
NAFLD-HCC (n = 32), NAFLD-cirrhosis (n = 28), non-NAFLD control (n = 30)	Significant enrichment of Bacteroides xylanisolvens, Ruminococcus gnavus, and Clostridium bolteae in NAFLD-HCC and NAFLD-cirrhosis	[100]

NASH: Non-alcoholic steatohepatitis; HC: Healthy controls; NAFLD: Non-alcoholic fatty liver disease; HS: Hepatic steatosis; SS: Simple steatosis; HCC: Hepatocellular carcinoma; MAFLD: Metabolic dysfunction-associated fatty liver disease; NAFL: Non-alcoholic fatty liver.