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

Table 3 Clinical trials on microbiota-targeted interventions in non-alcoholic fatty liver disease

Number of participants	Intervention	Outcome	Ref.
n = 20	L. rhamnosus GG	Significant decrease in ALT and antipeptidoglycan-polysaccharide antibodies, no effect on BMI Z score and visceral fat	[280]
n = 44	VSL#3	Improvement in NAFLD and reduction in triglycerides and insulin resistance	[311]
n = 28	L. bulgaricus and S. thermophilus	Reduction in the levels of ALT, AST, and GGT	[315]
n = 20	Lepicol probiotic (L. plantarum, L. delbrueckii, L. acidophilus, L. rhamnosus and B. bifidum)	Reduction in intrahepatic triglyceride and serum AST, no change in waist circumference, BMI, and glucose and lipid levels	[316]
n = 72	Probiotic yogurt containing L. acidophilus La5 and B. lactis Bb12	Reduction in the levels of ALT, AST, total cholesterol, and LDL cholesterol	[317]
n = 42	Lactocare (L. casei, L. acidophilus, L. rhamnosus, L. bulgaricus, B. breve, B. longum, S. thermophilus)	Reduction in insulin, insulin resistance and inflammation markers such as TNF-α and IL-6	[318]
n = 64	Probiotic mixture (L. acidophilus ATCC B3208, B. lactis DSMZ 32269, B. bifidum ATCC SD6576, and L. rhamnosus DSMZ 21690)	Reduction in waist circumference, cholesterol, triglycerides, LDL-C, ALT and AST. No change in weight, BMI, and BMI Z score	[319]
n = 65	Probiotic mixture (L. acidophilus, L. rhamnosus, L. paracasei, Pediococcus pentosaceus, B. lactis, and B. breve)	Reduction in body weight, total body fat, and intrahepatic fat	[320]
n = 58	“Symbiter” containing 14 probiotic belonging to Bifidobacterium, Lactobacillus, Lactococcus, and Propionibacterium	Reduction in fatty liver index, liver stiffness, serum AST, GGT, TNF-α and IL-6	[321]
n = 39	Multi-strain probiotics containing six different Lactobacillus and Bifidobacterium spp.	Stabilization of the mucosal immune function. No effect on hepatic steatosis and fibrosis levels	[322]
n = 40	Akkermansia muciniphila	Improvement in insulin sensitivity, reduction in insulinemia, plasma total cholesterol, levels of the markers for liver dysfunction and inflammation	[334]
n = 22	Inulin-type fructans	Increased fecal Bifidobacterium. No effect on liver fat contents, liver function tests, and metabolic and inflammatory mediators	[375]
n = 197	Resistant starch	Reduction in intrahepatic triglyceride content and liver enzymes	[382]
n = 66	Synbiotic (B. longum with FOS)	Significant reduction in inflammatory markers, LDL cholesterol, steatosis, and NASH activity index	[395]
n = 52	Protexin (L. casei, L. rhamnosus, L. acidophilus, L. bulgaricus, B. breve, B. longum, S. thermophilus with prebiotic FOS)	Significant attenuation in inflammatory markers, such as ALT, AST, GGT, high-sensitivity CRP, TNF-α, and NF-κB p65	[397]
n = 50	Protexin (L. casei, L. rhamnosus, L. acidophilus, L. bulgaricus, B. breve, B. longum, S. thermophilus with prebiotic FOS)	Reduction in inflammatory mediators, hepatic steatosis and fibrosis	[398]
n = 104	Synbiotic (FOS and B. animalis subspecies lactis BB-12)	Alteration in fecal microbiota. No effect on liver fat content or markers of liver fibrosis	[406]
n = 21	Fecal microbiota transplantation	Reduction in small intestinal permeability. No improvement in insulin resistance and hepatic proton density fat fraction	[418]

L. rhamnosus: Lactobacillus rhamnosus; L. bulgaricus: Lactobacillus bulgaricus; S. thermophilus: Streptococcus thermophilus; L. acidophilus: Lactobacillus acidophilus; L. plantarum: Lactiplantibacillus plantarum; L. paracasei: Lactobacillus paracasei; L. casei: Lactobacillus casei; B. breve: Bifidobacterium breve; B. longum: Bifidobacterium longum; B. bifidum: Bifidobacterium bifidum; FOS: Fructo-oligosaccharides; B. animalis: Bifidobacterium animalis; B. lactis: Bifidobacterium lactis; ALT: Alanine aminotransferase; BMI: Body mass index; NAFLD: Non-alcoholic fatty liver disease; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase; LDL: Low-density lipoprotein; TNF: Tumor necrosis factor; IL: Interleukin; LDL-C: Low density lipoprotein-cholesterol; NASH: Non-alcoholic steatohepatitis; CRP: C-reactive protein; NF-κB: Nuclear factor kappa B.