Table 1.

NAFLD interventions regulate gut microbiota and its derivatives.

Types	Reference	Intervention	Study subjects	Sample source	Changes in microbial metabolites	Changes in microbiota	Effects on steatosis
Prebiotics	Kundi et al.127	OAT, RYE (10% and 10% per day for 17 weeks)	WD-fed mice	Cecum content-SCFAs and microbiome Feces-BAs	Up – butyrate, propionate, acetate, T-βMCA Down – CA, DCA	Up – Bacteroidetes/Firmicutes ratio	Unchanged
	Hong et.al.22	astragalus polysaccharides (8% per day for 4 weeks)	HFD-fed mice	Cecum content	Up – purine metabolism Down – glutathione metabolism	Up – Bacteroidetes Down – Actinobacteria, Firmicutes, Proteobacteria	Decreased
	Xu et al.79	Sulforaphane (25 mg/kg/day for 6 weeks)	HFD-fed mice	Serum and liver tissue-IAA Feces-microbiome	Up – IAA	Up – Bifidobacterium, Romboutsia, Ruminococcaceae_UCG-014 Down – Firmicutes/Bacteroidetes ratio	Decreased
	Ma et al.139	Ferulic acid (30 mg/kg/day for 12 weeks)	HFD-fed ApoE-/- mice	Serum-metabolites Cecum content-microbiota	Up – I3A	Up – Bacteroidetes Down – Firmicutes	Decreased
	Huang et al.109	Monascus purpureus-fermented common buckwheat (1000 mg/kg/day for 8 weeks)	HFD-fed mice	Feces	Up – acetate, propionate, butyrate, BAs	Up – Ruminiclostridium, Lacobacillus Alistipes Down – Bacteroidales S24-7 group, Clostridiales XIII	Decreased
	Ye et al.71	Sodium butyrate (0.6 g/kg/d for 6 weeks)	MCD diet-fed mice	Feces	Up – stearic acid, behenic acid, oleic acid, linoleic acid, squalene Down – arachidonic acid	Up – Akkermansia, Roseburia, Coprococcus, Coprobacillus, Delftia, Sutterella, Coriobacteriaceaegenera Down – Bilophila, Rikenellaceae	Decreased
	Amerikanou et al.140	Mastiha (2.1 g/day for 6 months)	NAFLD patients (n = 98)	Feces-microbiota Serum-metabolites	Up – DCA Down – CA	Up – Faecalibacterium Down – Flavonifractor, Prevotella, Enterobacteriaceae, Bacteroides	Decreased PDFF only in obesity
Probiotics	Miccheli et al.141	VSL#3 (1–2 sachets/day for 4 months)	NAFLD children (n = 31)	Urine	Down – 2-HIB	/	steatosis grade reduced (evaluated by ultrasound)
	Jena et al.102	VSL#3 (109 cfu, QW for 7 months)	WD-fed FXR KO mice	Serum and liver tissue-metabolites Cecum content-microbiota	Up – CA, CDCA, UDCA, LCA, TLCA Down – DCA, HDCA	Up – Lachnospiraceae, Ruminococcus Faecalibacterium Down – Bacteroidaceae, Porphyromonadaceae, Helicobacteraceae	Decreased
	Ahmed et al.41	L. reuteri plus MTZ plus MTF (2 × 109 colony forming unit/day for 8 weeks; 15 mg/kg/day for 1 week; 150 mg/kg/day for 8 weeks)	HFD-fed male rats	Feces	Restore the ratio of acetate: propionate: butyrate	/	Decreased
BAs metabolism modulators	Zhang et al.142	Gly-MCA (10 mg/kg for 8 weeks)	HDF-fed mice	Cecum content	Up – T-α-MCA, T-β-MCA Down – acetate, propiorate, butyrate	Up – Bacteroidetes Down – Lactobacillus, Firmicutes Actinobacteria	Downregulated FAs synthesis gene expression
	Zhang et al.143	OCA (30 mg/kg/day for 12 weeks)	HFD-fed mice	Feces	Up – CA, α-MCA, βMCA Down – TCA, DCA	Up – Blautia, Desulfovibrio, Mucispirillum, Ruminiclostridium, Anaerotruncus Down – Bacteroides, Parabacteroides	Decreased
	Clifford et al.112	GSK2324 (30 mg/kg/day for 3 days)	WD-fed mice	Cecum content, liver tissue, and gall-bladder	Up – T-β-MCA Down – TCA, CA	/	Decreased hepatic TG
	Matsui et al.93	IBATi (2.5 μmol/kg/day for 6 weeks)	HFD-fed mice	Feces	Down – LCA, ω-MCA, βMCA	Up – α-diversity Down – Streptococcaceae	Decreased

ApoE, apolipoprotein E; BAs, bile acids; CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; Down, downregulate; FAs, fatty acids; FXR, farnesoid X receptor; Gly-MCA, glycine-β-muricholic acid; HDCA, hyodeoxycholic acid; HFD, high-fat diet; I3A, indole-3-aldehyde; 2-HIB, 2-hydroxybutyrate; IAA, indole-3-acetic acid; IBATi, ileal bile acid transporter inhibitor; KO, knockout; LCA, lithocholic acid; L. reuteri, Lactobacillus reuteri; MCD, methionine-choline-deficient; MTF, metformin; MTZ, metronidazole; NAFLD, non-alcoholic fatty liver disease; OAT, oat bran; OCA, obeticholic acid; PDFF, proton density fat fraction; RYE, rye bran; SCFAs, short-chain-fatty acids; T-βMCA, tauro-β-muricholic acid (T-βMCA); TG, triglyceride; TLCA, taurine-lithocholic acid; UDCA, ursodeoxycholic acid; Up, upregulate; WD, western diet; T-α-MCA, tauro-α-muricholic acid.