Table 3.
RCTs addressing the therapeutic modulation of the gut microbiome in NAFLD patients
| Study | Study design | Bacterial species | Condition | Main outcome telated to NAFLD |
|
|---|---|---|---|---|---|
| Biochemistry | Imaging/biopsy | ||||
| Malaguarnera et al. [185] (2012) | RCT (n=66) | Bifidobacterium+fructooligosaccharide | NASH | (↓) AST, endotoxins | Biopsy: steatosis & NASH improved |
| 24 weeks | (-) ALT, glucose, BMI | ||||
| Shavakhi et al. [186] (2013) | Double-blind RCT (n=64) | Lactobacillus, Bifidobacterium, Streptococcus | NASH on metformin | (↓) ALT, AST | US: hepatic steatosis improved |
| 6 months | |||||
| Wong et al. [187] (2013) | RCT (n=20) | Lactobacillus, Bifidobacterium | NASH | (↓) AST | MRS: hepatic steatosis improved |
| 6 months | (-) BMI, glucose | ||||
| Alisi et al. [188] (2014) | Double-blind RCT (n=44) | Lactobacillus, Bifidobacterium, Streptococcus | NAFLD children | (↓) BMI | US: hepatic steatosis improved |
| 4 months | (-) ALT, TG | ||||
| Eslamparast et al. [189] (2014) | Double-blind RCT (n=52) | Lactobacillus, Bifidobacterium, Streptococcus+fructooligosaccharide | NAFLD | (↓) ALT, AST | Transient elastography: liver stiffness improved |
| 28 weeks | |||||
| Asgharian et al. [190] (2016) | Double-blind RCT (n=80) | Lactobacillus, Bifidobacterium, Streptococcus+fructooligosaccharide | NAFLD | (-) AST, ALT | US: hepatic steatosis improved |
| 8 weeks | |||||
| Ferolla et al. [191] (2016) | RCT (n=50) | Lactobacillus+inulin | NASH | (↓) BMI | MRI-PDFF: steatosis improved but no change in liver fibrosis |
| 3 months | (-) AST, ALT, LPS, intestinal permeability | ||||
| Famouri et al. [192] (2017) | Triple-blind RCT (n= 64) | Lactobacillus, Bifidobacterium | NAFLD obese children | (↓) ALT, AST, cholesterol, TG | US: hepatic steatosis improved |
| 12 weeks | (-) BMI | ||||
| Manzhalii et al. [193] (2017) | RCT (n=75) | Lactobacilli, Bifidobacteria, Streptococcus | NASH on a ↓ fat diet | (↓) ALT, BMI, cholesterol | Transient elastography: liver stiffness improved |
| 12 weeks | |||||
| Mofidi et al. [194] (2017) | Double-blind RCT (n=50) | Lactobacillus, Bifidobacterium, Streptococcus+fructooligosaccharide | NAFLD | (↓) AST, ALT, glucose, TG, cholesterol | Transient elastography: hepatic steatosis & liver stiffness improved |
| 28 weeks | |||||
| Bakhshimoghaddam et al. [195] (2018) | RCT (n=102) | Bifidobacterium+inulin | NAFLD | (↓) AST, ALT, GGT, TG, cholesterol | US: hepatic steatosis improved |
| 24 weeks | |||||
| Kobyliak et al. [196] (2018) | Double-blind RCT (n=48) | Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium, Acetobacter+omega-3 fatty acids | NAFLD with T2DM | (↓) TG, cholesterol, FLI | SWE: no significant change in liver stiffness |
| 8 weeks | (-) AST, ALT | ||||
| Kobyliak et al. [197] (2018) | Double-blind RCT (n=58) | Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium, Acetobacter | NAFLD with T2DM | (↓) AST, FLI | SWE: no significant change in liver stiffness |
| 8 weeks | (-) ALT, TG, cholesterol | ||||
| Sayari et al. [198] (2018) | RCT (n=138) | Lactobacillus, Bifidobacterium, Streptococcus+fructooligosaccharide | NAFLD taking sitagliptin | (↓) glucose, AST, cholesterol | |
| 16 weeks | (-) ALT, TG, BMI | ||||
| Wang et al. [199] (2018) | Double-blind RCT (n=200) | Bifidobacterium, Lactobacillus, Enterococcus, Bacillus | NAFLD | (↓) AST, ALT, TG, cholesterol | US: no significant change in hepatic steatosis |
| 1 month | |||||
| Ahn et al. [200] (2019) | Double-blind RCT (n=68) | Lactobacillus, Pediococcus, Bifidobacterium | NAFLD with obesity | (↓) TG | MRI-PDFF: hepatic steatosis improved transient elastography: no significant change in liver stiffness |
| 12 weeks | (-) AST, ALT, LPS, cholesterol, glucose | ||||
| Duseja et al. [201] (2019) | Double-blind RCT (n=30) | Lactobacillus, Bifidobacterium, Streptococcus | NAFLD | (↓) ALT, LPS | Biopsy: improved NAS score, hepatocyte ballooning & fibrosis |
| 1 year | (-) AST | ||||
| Scorletti et al. [202] (2020) | Double-blind RCT (n=104) | Bifidobacterium+fructooligosaccharide | NAFLD | (-) ELF score | MRS: no significant change in hepatic steatosis |
| 10–14 months | |||||
RCT, randomized controlled trials; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; AST, aspartate transaminase; ALT, alanine transaminase; BMI, body mass index; US, ultrasound; MRS, magnetic resonance spectroscopy; TG, triglyceride; LPS, lipopolysaccharide; MRI-PDFF, magnetic resonance imaging derived proton density fat fraction; GGT, gamma-glutamyl transferase; T2DM, type 2 diabetes mellitus; FLI, fatty liver index; SWE, shear wave elastography; NAS, NAFLD activity score; ELF, enhanced liver fibrosis.