Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

Table 3 Studies with probiotics in human non-alcoholic fatty liver disease

Ref.	Probiotic(s)	Study design	Month	Main results	ALT or AST	GGT	US/MRI/LH
Wong et al[87]	Lepicol: 10 g/d10 adult NASH ctrls10 adult NASH patients	RCT	6	Significantly reduced ASTChanged intrahepatic triglyceride content (IHTG)	Pr vs plac: ALT NS decrease AST: -13 ± 31 vs 23 ± 32, P = 0.021	NR	Reduced IHTG at SMR (P = 0.034)
Vajro et al[73]	Lactobacillus GG: 12 billion CFU/d 10 pediatric obese ctrls 10 pediatric obese patients	RCT	2	Significantly reduced aminotransferases and anti-peptidoglycan-polysaccharide Abs. TNF-α stable	Pr vs plac: Decreased ALT 70.3 ± 34.76 vs 40.1 ± 22.37, P = 0.03	Normal	Unchanged
Loguercio et al[81]	Bio-Flora: 4 tablets/d 10 adult NASH patients	Open label	2	Decreased ALT and GGT	Decreased ALT -64.5% ± 26.5%, P < 0.01	-55 ± 31, P < 0.01	NR
Loguercio et al[82]	VSL#3: 450 billion/d 22 patients	Open label	NR	Significantly improved plasma MDA and 4-HNE (data not shown)	NR	NR	NR
Solga et al[84]	VSL#3: 450 billion/d 4 adult NAFLD patients	Open label	4	Significantly increased ultrasound liver fat NS different glycosylated Hb; TNF-α, IL-6	Unchanged	NR	Increased liver fat at MRS
Aller et al[85]	Lactobacillus bulgaricus streptoc.	RCT	3	Significantly reduced aminotransferases	Decreased in Pr:ALT: 67.7 ± 25.1 vs 60.4 ± 30.4, P < 0.05AST: 41.3 ± 15.5 UI/L vs 35.6 ± 10.4 UI/L, P < 0.05	118 ± 63 vs 107 ± 60 (P < 0.05)	NR
	Thermophiles: 500 million CFU/d
	14 adult NAFLD ctrls
	14 adult NAFLD patients
Malaguarnera et al[86]	Bifidobacterium longum and Fos: 2.5 g/d + vit B1, B2 , B6, B12 + life style 34 adult NASH ctrls 32 adult NASH patients	RCT	4	Improved fibrosis scores in 70% of patients. Reduced HOMA-IR, LDL cholesterol , CRP, TNF-α, AST	Pr vs plac: ALT NS decrease AST -69.6 vs -45.9, P = 0.05	NR	Decreased US bright liver -42% vs -11%, P < 0.001
Shavakhi et al[91]	Proxetin: 2 tablets/d	RCT	6	Significantly reduced ALT in Metformin/	Pr vs plac:ALT Decrease45.2 ± 32.5 vs 112.5 ± 69,P < 0.001	NR	Reduced US grade in M/Pr, P < 0.01
	Metformin: 500 mg/d			Probiotic (M/Pr) vs M/
	36 adult NASH ctrls			placebo (M/Plac)
	34 adult NASH patients			M reduced BMI enhanced by Pr
Eslamparast et al[89]	Proxetin 2 tablets/d26 adult NASH ctrls26 adult NASH patients	RCT	6	Significantly and persistently reduced ALT Significantly reduced AST, HOMA-IR, GGT, CRP, TNF-α, and NF-κB p65	Pr vs placDecreased ALT (wk) 28 -25.1 vs -7.3, P < 0.001	Reduced Pr vs plac-15.8 vs -5.21, P < 0.01	Significant improvement elastography and fibrosis score
Alisi et al[90]	VSL#3	RCT	4	Significantly increased GLP-1 and aGLP-1 Sign. decreased BMI	Pr vs plac ALT unchanged	NR	Significantly improved ultrasound fatty liver score

Proxetin: Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium breve, Bifidobacterium longum, Streptococcus thermophilus + FOS 350 mg; Lepicol: Lactobacillus plantarum, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium bifidum (Each sachet contains 10 g of probiotic cultures) + FOS; VSL#3: Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. bulgaricus; BioFlora: Lactobacilli (acidophilus; lactis; casei; brevis; salivarum; rhamnosus; plantarum; bulgaricus), iron, vitamin C, B6, D3, B2, B12, folic acid and zinc oxide, + FOS; FOS: Fructooligosaccharides; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transpeptidase; MRI: Magnetic resonance imaging; LH: Liver histology; BMI: Body mass index; NR: Not reported; Pl: Placebo; Pr: Probiotic; NS: Not significant; Sign: Significantly; TNF: Tumor necrosis factor; IL: Interleukin.