Table 4.

Treatment targeting dysbiosis in non-alcoholic fatty liver disease.

Conditions		Treatment	Main Results	Ref.
Human	Randomized, triple blind trial (64 children with NAFLD)	Probiotic capsule (L. acidophilus, B. bifidum, B. lactis, L. rhamnosus), 12 weeks or placebo	Probiotic treatment group - enhanced liver enzyme -↓ mean cholesterol, LDL-cholesterol, triglyceride, waist circumference	[111]
Human	Open-label, randomized controlled clinical trial (n = 102)	300 g synbiotic yogurt (B. animalis, inulin)	Synbiotic yogurt consumption group - improved hepatic steatosis and liver enzyme	[112]
		or conventional yogurt, 24 weeks or control group
Human	Obese NAFLD (n = 68)	Probiotic mixture (L. acidophilus, L. rhamnosus, Lacticaseibacillus paracasei, P. pentosaceus, B. lactis, and B. breve) 12 weeks or placebo	Probiotic treatment -↓ body weight and total body fat	[113]
Human	NAFLD (n = 89)	Probiotic (L. casei, L. rhamnosus, L. acidophilus, B. longum, and B. breve) or prebiotic (oligofructose), 12 weeks or placebo	Probiotics group -↓ triglyceride, AST, ALT, GGT, ALP	[114]
			Prebiotics group -↓ triglyceride, LDL-cholesterol, AST, ALT
C57BL/6J mice		ND/HFD/ND + inulin/HFD + inulin for 14 weeks	Inulin treatment group -restored abnormal indicators observed in HFD group -reduced TLR4 + hepatic macrophages, NF-κB, nod-like receptor protein 3, apoptosis-associated speck-like protein and caspase-1 -↑ Akkermansia, Bifidobacterium ↓ Blautia, the ratio of Firmicutes/Bacteroidetes - increase short-chain fatty acids	[117]
Human	14 patients with liver biopsy-confirmed NASH	Randomized to receive oligofructose (8 g/day) for 12 weeks followed by 16 g/day for 24 weeks or isocaloric placebo for 9 months	Oligofructose improved liver steatosis and overall NAS score	[118]
Human	Adult with definite NASH, NAS score ≥ 4, F2-3 or F1 with at least one accompanying comorbidity	Randomly assigned in 1:1:1 oral placebo: n = 311 obeticholic acid 10 mg: n = 312 obeticholic acid 25 mg: n = 308	Obeticholic acid at 25 mg significantly improved fibrosis and key components of NASH disease activity	[119]
Human	NAFLD patients, n = 198	Randomly assigned in 1:1:1 placebo (n = 64) norursodeoxycholic acid 500 mg/day (n = 67) norursodeoxycholic acid 1500 mg/day (n = 67) for 12 weeks	Norursodeoxycholic acid at 1500 mg resulted in a significant reduction of serum ALT within 12 weeks	[120]

NAFLD, non-alcoholic fatty liver disease; LDL, low-density lipoprotein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; ALP, alkaline phosphatase; TLR, Toll-like receptor; NF-Κb, nuclear factor kappa-light-chain-enhancer of activated B cells; ND, normal diet; HFD, high fat diet; NASH, non-alcoholic steatohepatitis; NAS, non-alcoholic fatty liver activity score.