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

Table 2 Studies with probiotics in animal models of non-alcoholic fatty liver disease

Ref.	Animal model	Probiotic	Weeks	Positive effects	Negative effects
Li et al[63]	HFD ob/ob mice	VSL#3	4	Reduced liver inflammation and serum ALT
Esposito et al[64]	HFD Sprague-Dawley rats	VSL#3	4	Significantly reduced TNF alpha levels, MMP-2 and MMP-9 activities, iNOS, and Cox-2 expression. Increased PPAR-alpha expression	NS
Ma et al[65]	HFD-WT male C57BL6	VSL#3	4	Improved NKT cells depletion, insulin resistance, and hepatic steatosis	NS
Velayudham et al[66]	MCD mouse	VSL#3	10	Prevented PPAR-induced fibrosis. Increased expression of Bambi, a negative regulator of the TGFβ signaling pathway	Did not prevent NASH.
					Did not protect against MCD liver injury
Mencarelli et al[67]	Apo E-/- mice fed dextran sulfate sodium	VSL#3	12	Reversed IR and prevented steatohepatitis by transactivation of PPARγ	NS
Bhathena et al[68]	MCD Bio F1B Golden Syrian hamster	Lactobacillus fermentum ATCC	12	Reduced liver fat deposition, decreased total cholesterol, triglycerides, uric acid, and insulin resistance	NS
Wagnerberger et al[69]	High fructose intake C57BL/6 L mouse	Lactobacillus Casei-Shirota	8	Attenuated the TLR4 signaling pathway and increased PPAR activity
Karahan et al[70]	MCD Wistar rats	Pro1; Pro2	2 and 8	Both probiotics reduced ≥ 50% the incidence of steatohepatitis by modulating apoptosis + anti-inflammatory activity	NS
Yalçin et al[71]	Broilers fed low-protein diet	Primalac 454	4	Significantly diminished histological grade, steatosis and cell ballooning scores	Increased serum TG
Xu et al[72]	HFD Sprague-Dawley rats	Lactobacillus acidophilus Bifidobacterium longum	12	Bifidobacterium longum was superior to Lactobacillus acidophilus in attenuating liver fat accumulation. No variation of intestinal permeability in the treated groups
Nardone et al[74]	Ischemia/reperfusion (I/R) in rats fed a standard or MCD diet	Lactobacillus Paracasei	8	Reduced LPS levels. Attenuated I/R-related damage	NS
Fazeli et al[75]	Rats on high cholesterol diet	Lactobacillus plantarum A7	2	Significantly reduced levels of cholesterol, TG and LDL	NS
Endo et al[77]	Male Fischer CDAA rats	Butyrate producing Clostridium butyricum MIYAIRI 588	8, 16, 50	Delayed CDAA-induced NAFLD progression and liver tumorigenesis. Reduced lipid deposition and improved IR, serum endotoxin levels, and hepatic inflammatory indexes. Improved ZO-1 expression	NS
Chiua et al[78]	HepG2 cells exposed to LPS	Lactobacilli bacteria lisate		Suppressed cytokine signaling 1 and PPAR alpha via NOD-NF-κB and cross-regulation of TLR4	NS
Raso et al[76]	Rats on a HFD	Synbiotic with Lactobacillus paracasei B21060	6	Improved IR parametersReduced cytokine synthesis and restored the HFD-dysregulated TLR 2, 4 and 9 mRNAs.Preserved gut barrier integrity	NS

Primalac 454: Lactobacillus acidophilus, Lactobacillus casei, Enterococcus faecium, and Bifidobacterium thermophilus; VSL#3: Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus delbrueckii subsp. bulgaricus; Pro1: Lactobacillus fermentum, Lactobacillus plantarum, and Enterococcus faecium; Pro2: Enterococcus faecium and Lactobacillus Pl; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TNF: Tumor necrosis factor; IL: Interleukin; IR: Insulin resistance; PPAR: Peroxisome proliferator-activated receptors; MMP: Matrix metalloproteinase; NOS: Nitric oxide synthase; NOD: Nucleotide-binding oligomerization domain receptors; TLR: Toll-like receptors; CDAA: Choline-deficient, L-amino acid-defined; MCD: Methionine-choline deficient.