Table 2.
Primary outcomes, liver evaluation method, and main positive outcomes of randomized clinical trials of gut microbiota therapy in nonalcoholic fatty liver disease.
| Authors | Treatment & duration | Primary outcomes | Liver evaluation method | Main positive outcomes of microbiota therapy |
|---|---|---|---|---|
| Alisi et al. (2014) | Probiotics (4 months) | Fatty liver severity | Ultrasonography | Less severe hepatic steatosis, lower BMI, higher blood GLP-1, and α-GLP-1 |
| Kobyliak et al. (2018) | Probiotics (8 weeks) | FLI and liver stiffness | FLI and Shear Wave Elastography | More decreased FLI, serum AST, gamma-glutamyl transpeptidase, TNFα, and IL6 |
| Anh et al. (2019) | Probiotics, 12 weeks | VFA and IHF | MR | More decreased IHF and body weight |
| Sepideh et al. (2016) | Probiotics (8 weeks) | Not clarified | Not evaluated | Lower fasting blood sugar, insulin, HOMA-IR, and IL6 |
| Bomhof et al. (2019) | Prebiotics (36 weeks) | NAS score | Liver biopsy | Improved hepatic steatosis and NAS score |
| Behrouz et al. (2020) | Probiotics (12 weeks), prebiotics (12 weeks) | Not clarified | Not evaluated | Decreased serum leptin, insulin, and HOMA-IR in the probiotic and prebiotic groups and decreased fasting blood sugar only in the prebiotic group |
| Malaguarnera et al. (2012) | Synbiotics (24 weeks) | NASH activity index | Liver biopsy | Lower AST, low-density lipoprotein, C-reactive protein, TNFα, and HOMA-IR; better mitigated hepatic steatosis and NASH activity index |
| Ferolla et al. (2016) | Synbiotics (12 weeks) | Not clarified | MR | Reduction in liver steatosis, body weight, BMI, and waist circumstance |
| Shavakhi et al. (2013) | Synbiotics (6 months) | ALT, AST, and ultrasound grade of NASH | Ultrasound | Lower ALT, AST, BMI, blood triglyceride, and cholesterol. Lower grade of hepatic steatosis |
| Chen et al. (2019) | Synbiotics (24 weeks) | Not clarified | MR | Lower waist circumstance, HOMA-IR, hepatic fat fraction, intraheaptic lipid, serum LPS, and FGF21; higher GSH-Px and SOD |
| Scorletti et al. (2020) | Synbiotics (24 weeks) | Liver fat fraction, liver fibrosis score, and gut microbiota composition | MR | Altered fecal microbiota composition |
| Craven et al. (2020) | Fecal microbiota transplantation (6 months) | Insulin resistance | MR | Reduced small intestinal permeability without improved HOMA-IR and hepatic proton density fat fraction |
| Chong et al. (2020) | Prebiotics (12 weeks) + antibiotics (1 week) | ≥7% weight loss | Transient elastography | Lower ALT and AST |
ALT: alanine aminotransferase; AST: aspartate aminotransferase; BMI: body mass index; FGF21: fibroblast growth factor 21; FLI: fatty liver index; GGT: γ-glutamyl transferase; GLP: glucagon-like peptide; GSH-Px: glutathione peroxidase; HOMA-IR: homeostasis model assessment-insulin resistance; IHF: intrahepatic fat; IL6: interleukin 6; LPS: lipopolysaccharide; MR: magnetic resonance; NAS: non-alcoholic fatty liver disease activity score; NASH: non-alcoholic steatohepatitis; SOD: superoxide dismutase; TNFα: tumor necrosis factor α; VFA: visceral fat area.