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. 2018 Dec 18;9:1813. doi: 10.3389/fphys.2018.01813

Table 1.

Modulation of microbiota by probiotics on in vivo models of NAFLD.

References Animal model Probiotic Time Microbiota analysis Main outcomes
Kim et al., 2016 HFD-fed C57BL/6J mice Lactobacillus rhamnosus GG (1 × 108 CFU per mouse) 13 weeks Bacteroidetes
Firmicutes/Bacteroidetes ratio (no significant)
↓Hepatic fat accumulation
↓Serum triglycerides and cholesterol
↓PPARγ, SREBP1, CACC, FAS, GPAT, CD36 and ApoB100
↓IL-6 and IL12
Xue et al., 2017 HFHS-fed SPF SD rats Probiotic mixture containing 0.5 × 106 colony-forming units (CFU) live Bifidobacterium infantis and Lactobacillus acidophilus and 0.5 × 105 CFU live Bacillus cereus 12 weeks E.coli
Enterococcus
Bifidobacteria
Lactobacillus
Bacteroides
↓Liver inflammatory scoring
↓BWG Maintenance of tight junctions integrity and histology of the jejunum.
↑Occludin
↓LPS and TLR4
↓TNF-α, IL-18
↓ALT, AST, γ-GT ALP
↓TC, TG, LDL and FFA
↓HOMA-IR
Okubo et al., 2013 MCD-fed C57BL/6 mice Lactobacillus casei strain Shirota (109 CFU/day) 6 weeks Bifidobacterium
Lactobacillus (L. casei and L. reuteri)
↓Hepatic lipid content, inflammation, ballooning and fibrosis
↓LPS
↓α-SMA and TIMP-1
↓SREBP-1c and FAS
↓TNF-α
↓Colon inflammation (nuclear NF-κB/p65)
Wang et al., 2015 HFD-fed SPF C57BL/6J mice Lactobacillus paracasei CNCM I-4270, L. rhamnosus CNCM I-3690, and Bifidobacterium animalis subsp. lactis CNCM I-2494 6 weeks Strain specific modulation of key phylotypes belonging to: ↑Bifidobacterium
↑Olsenella
Barnesiella
Allobaculum
Butyrivibrio
Desulfovibrionaceae
Oscillibacter
Clostridium XIVa
↓Steatosis
↓BWG
↓HOMA-IR
↓Adipocyte size
↓CLS, MMP-12-positive cells and CD11c
↓Liver TNF-α (B. animalis)
↓LBP
↑Adiponectin (B. animalis)
Moya-Pérez et al., 2015 HFD-fed C57BL/6 mice Bifidobacterium pseudocatenulatum CECT 7765 14 weeks Allobaculum
Lactobacillus
Bifidobacterium
Alistipes
Lachnospiraceae
Dorea
Bacteroides
↓Steatosis
↓BWG
↓Cholesterol
↓Triglycerides
↑Insulin sensitivity
↓Epididymal adipose tissue
↓Endotoxemia/TLR4
↓Liver and systemic inflammation
Cano et al., 2013 HFD-fed C57BL/6 mice Bifidobacterium pseudocatenulatum CECT 7765 7 weeks Bifidobacterium spp.
Enterobacteriaceae
↓Steatosis
↓BWG
↓Leptin levels
↓IL6 MCP1
↑Insulin sensitivity
Kim et al., 2017 HFD-fed C57BL/6 mice Kefir milk contained 9.84 ± 0.36 log CFU/ml of lactic acid bacteria and 7.23 ± 0.41 log CFU/ml of yeast 12 weeks Firmicutes/Bacteroidetes
Lactobacillus
Lactococcus
Candida
Proteobacteria
Enterobacteriaceae
B. fragilis
↓NAS
↓BWG
↑PPARα AOX
↓IL-6
↓Total cholesterol and LDL
Everard et al., 2014b db/db mice Saccharomyces boulardii 4 weeks Saccharomyces and total yeast
Bacteroidetes
Firmicutes
Proteobacteria
Tenericutes
Prevotella
Bacteroides
↓Hepatic lipid content
↓BWG
↓Fat mass
↓CD11c, F4/80 and MCP-1
↓Liver IL-1β
↓Serum IL-4, IL-6, IL-1β and TNF-α

α-SMA, α-smooth muscle actin; ACC, acetyl-CoA carboxylase; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BWG, body weight gain; CLS, crown-like structures; FAS, fatty acid synthase; FFA, free fatty acids; γ-GT, gamma-glutamyltransferase; GPAT, glycerol phosphate acyltrasferase; HOMA-IR, homeostasis model assessment of insulin resistance; IL, interleukin; LBP, lipopolysaccharide-binding protein; LDL, low-density lipoprotein; LPS, lipopolysaccharide; MCP-1, monocyte chemoattractant protein 1; MMP-12, matrix metalloproteinase-12; NAS, NAFLD activity score; NF-κB, nuclear factor kappa B; PPARγ, peroxisome proliferator-activated receptor gamma; SREBP-1c, sterol regulatory element-binding protein 1c; TC, total cholesterol; TG, triglycerides; TIMP-1, metalloproteinase 1; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor.