Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease

Table 1 Summary of clinical trials using probiotics to treat nonalcoholic fatty liver disease patients

Ref.	Sample size and underlying hepatic disorder	Design	Intervention	Duration	Results after treatment
Loguercio et al[12]	12 chronic HCV infection 10 alcoholic cirrhosis 10 NASH (biopsy-proven)	Prospective, single-center, nonrandomized, noncontrolled pilot study	Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus. rhamnosus, Lactobacillus. plantarum, Lactobacillus. salivarius, Lactobacillus. bulgaricus, Lactobacillus. casei, Bifidobacterium. lactis and Bifidobacterium. breveassociated plus FOS, vitamins and minerals	2 mo	NASH patients: decreased serum ALT, GGT, MDA, 4-HNE and TNF-α
Loguercio et al[13]	22 NAFLD (biopsy-proven) 20 alcoholic cirrhosis 20 chronic HCV infection 16 liver cirrhosis (without any other information)	Prospective, single-center, nonrandomized, noncontrolled	VSL#3 - 900 billion/2 × d	3 mo	NAFLD and alcoholic cirrhosis groups, improved MDA, 4-HNE. All groups improved S-NO plasma levels
Solga et al[14]		Open label pilot trial	VSL ≠3 - 450 billion/d	4 mo	All increase steatosis. No significant changes in metabolic panel, protime, glycosylated hemoglobin, TNF-α, IL-6 and 1β, and interferon-γ
Vajro et al[15]	20 NAFLD children (10/10) (US + increased aminotransferases)	Randomized, double-blind, placebo-controlled trial	Lactobacillus rhamnosus GG (12 billion CFU/d) vs placebo	8 wk	Improvement of ALT antipeptidoglycan-polysaccharide antibodies levels. No alterations in BMI z score, visceral fat, TNF-α levels and in US bright liver parameters
Aller et al[16]	28 (14/14) NAFLD (biopsy-proven)	Randomized, double-blind, placebo-controlled trial	L. bulgaricus and Streptococcus thermophiles (500 million CFU/d) vs placebo	3 mo	Improvement of AST, ALT and GGT levels No changes in anthropometric parameters and cardiovascular risk factors
Malaguarnera et al[17]	66 (34/32) NAFLD (biopsy-proven)	Randomized, double-blind, placebo-controlled trial	Bifidobacterium longum + FOS vs placebo	24 wk	Improvement of TNF-α, CRP, AST, HOMA-IR and endotoxin levels, steatosis, and the NASH activity index
Wong et al[18]	20 (10/10) NAFLD (biopsy-proven)	Randomized, double-blind	Lepicol probiotic formula vs nothing	6 mo	Improvement of AST levels and IHTG No differences in BMI, waist circumference, glucose and lipid levels
Eslamparast et al[19]	52 NAFLD (US, liver enzymes and fibroScan)	Randomized, double-blind, placebo-controlled trial	Synbiotic (200 million of 7 strain + FOS + probiotic cultures [magnesium stearate (source: mineral and vegetable) + vegetable capsule (hydroxypropyl methyl cellulose vs placebo	28 wk	Improvement of ALT, AST, GGT, CRP, TNF-α and total nuclear factor k-B levels, and fibrosis score

NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatites; HCV: Hepatitis C virus; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transpeptidase; MDA: Malondialdehyde; 4-HNE: 4-hydroxynonenal; TNF-α: Tumor necrosis factor; FOS: Fructooligosaccharides; VSL#3: Mixture of probiotics; S-NO, snitrosothiols; CFU: Colony-forming unit; BMI: Body mass index; US: Ultrasound; AST: Aspartate aminotransferases; CRP: C reactive protein; HOMA-IR: Homeostasis model assessment of insulin resistance; IHTG: Intrahepatic triglycerides; US: Ultrasound.