TABLE 3.

Trials on the exploring of therapeutic strategy target to gut microbiota.

Study	Participant details and Treatment strategy	Effect of treatment
Zhao et al. (43)	Male C57BL/6J mice were fed an HFD for 8 weeks along with the indicated interventions. BBOX-knockout mice (BBOX–/–) were administered TMAVA.	Improve energy production and conversion, and carbohydrate transport and metabolism, and a decrease in lipid transport and metabolism. Improve hepatic mitochondria function
Xie et al. (12)	C57BL/6 mice were divided into four groups: CTL group, model (M) group, model + VVYP 10 mg/kg (M-VVYP), VVYP 10 mg/kg (VVYP).	VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction. VVYP increased the abundance of Eubacteriaceae, coriobacteriaceae, Desulfovibrionaceae, S24-7 and Bacteroidia VVYP reduced the abundance of Lactobacillus. VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)-associated genes, inhibited subsequent liver inflammatory responses.
Craven et al. (1)	21 patients with NAFLD were randomly assigned to receive an allogenic or autologous FMT for 6 months post-transplant.	Allogenic FMT patients with elevated small intestinal permeability at baseline had a significant reduction 6 weeks after allogenic FMT. No significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT.
Geng et al. (95)	Zebrafish model, and NAFLD rats model were divided into: control, high-fat (HF) diet, and HF diet plus different probiotics including ZW3.	Supplementation with ZW3 could improve the liver impairments and reduce inflammation through TLR4-MyD88 and JNK signaling pathways. ZW3 modulated gut microbiota by promoting relative abundance of Firmicutes and Lactobacillus, decreasing the abundance of Escherichia Shigella and Bacteroides.
Lensu et al. (49)	Male Wistar rats were divided into four dietary treatment groups: (1) HFD, (2) HFD supplemented with XOS, (3) control, and (4) LFD supplemented with XOS	XOS increased the growth of F. prausnitzii, lowered the level of cecal tyrosine, XOS decreased triglycerides on the. HFD, XOS increased the hepatic activity of β-HAD on the HFD, XOS supplementation seemed to ameliorate mitochondrial respiration injury induced by HFD, XOS had increased respiratory capacity available for the production of ATP through the electron flow from complex I, improved coupling of electron transport through complex I and oxidative phosphorylation. XOS diminished the epithelial injury caused by the HFD
Carbajo-Pescador et al. (56)	Wistar rats were separated into two subgroups (n = 24): Control, semi-purified high fat diet (HFD)	Exercise performance counteracted the HFD induced microbial imbalance, modifying Firmicutes/Bacteroidetes ratio.
Zhang et al. (84)	C57BL/6J male mice were divided into: normal diet, HFD, HFID (high-fat plus resistant dextrin diet)	Resistant dextrin ameliorated mitochondrial function and hepatic steatosis by manipulating the intestinal microbiota and its metabolites. Resistant dextrin supplementation via an HFID diet restored the structure of the intestinal microbiota, ameliorated microbial metabolic changes including to tryptophan and bile acid metabolism, decreased intestinal permeability and inflammatory cytokine levels, retained a healthy gut microenvironment, improved mitochondrial function, and ameliorated hepatic steatosis.
Li et al. (28)	Male C57BL/6 mice were divided into: normal diet, HFHC diet, HFHC diet supplemented with UDCA.	UDCA could ameliorate hepatic inflammation, and partially restore the dysbiosis of the gut microbiota for the treatment of NASH. UDCA could protect against intestinal barrier disruption and reduce serum levels of LPS and inflammatory cytokines in NASH mice.
Derosa et al. (89)	NAFLD patients were randomized to take placebo or VSL#3, 2 sachets/day for 3 months.	Tg, Hs-CRP, γ-GT, AST/ALT decrease, hepatic steatosis index (HSI) were improved.
Nor et al. (87)	NAFLD patients were supplemented with either a probiotics sachet (MCP®, BCMC® strains) for 6 months.	Decrease the expression of CD8+ T lymphocytes and ZO-1 (Z-score), no improvement in the hepatic steatosis, fibrosis, and inflammatory activity scores.
Crommen et al. (86)	Obese patients with NAFLD received a combination of probiotic and a specific micronutrient mixture or a basic care micronutrient mixture for 12 weeks.	Improve serum AST, NAFLD fibrosis score, Tg and the visceral adiposity index.
Chong et al. (88)	Patients with NAFLD were randomly to take 2 sachets VSL#3® probiotic or placebo twice daily for 10 weeks.	VSL#3® probiotic supplementation did not significantly improve insulin resistance, endothelial dysfunction, oxidative stress, inflammation or liver injury in patients with NAFLD.

TMAVA, N,N,N-trimethyl-5-aminovaleric acid; HFD, high-fat diet; NC, normal chow; HFLC, high-fat/low-cholesterol diet; HFHC, high-fat/high-cholesterol diet; FMT, fecal microbiota transplantation; XOS, xylo-oligosaccharides; PDFF, hepatic proton density fat fraction; IR, insulin resistance; UDCA, ursodeoxycholic acid; TG, triglycerides; Hs-CRP, high-sensitivity C-reactive protein; γ-GT, transaminases and gamma-glutamyltransferase; HIS, hepatic steatosis index; HOMA-IR, insulin resistance.