TABLE 2.

Studies evaluating the effects of dietary factors on the gut microbiota in animal models of NAFLD¹

Study, year (ref)	Animal model	Treatment	Method(s)	Main results
Saha and Reimer, 2014 (53)	Wistar rats	HF or HP diet from 3 to 15 wk of age; a high-fat, high-sucrose diet from 15 to 21 wk; the respective HF or HP diets from 21 to 25 wk	qPCR	HF vs. control group:
				↑Total bacteria, ↑Bifidobacteria, and ↑Bacteroides:Prevotella
				HF vs. HP:
				↓Firmicutes, ↓Firmicutes:Bacteroidetes, ↓hepatic cholesterol content
				Negative correlation between liver weight and Bacteroides:Prevotella (r = −0.415, P = 0.044)
Bomhof et al., 2014 (54)	Sprague-Dawley rats	Initiate with a high-fat, high-sucrose diet for 8 wk and then prebiotic OFSs vs. the probiotic BB-12 for 8 wk	qPCR	Prebiotic oligofructose vs control:
				↓Energy intake, ↓ weight gain, ↓fat mass, ↑PYY, ↑Bifidobacteria, ↑Lactobacilli
				Improved glycemia and ↓insulin concentrations, ↓liver TGs in OFSs and BB-12
				↑GLP-1 in OFSs
				↑GLP-2 in probiotic BB-12
				No differences in plasma LPS, TNF-α, IL-6, IL-1β
Ritze et al., 2014 (55)	C57BL/6 mice	High-fructose diet with LGG vs. high-fructose diet over 8 wk	qPCR	High-fructose diet with LGG vs. high-fructose diet:
				↓ALT, ↓fat, ↓accumulation in liver, ↓ChREBP, ↓ACC1, ↓FAS, ↓TNF-α, ↓IL-1β, ↑occludin, ↓LPS, ↑total bacterial numbers
Zeng et al., 2013 (56)	C57BL/6 mice	HFD vs. LFD for 10 wk	Sequencing 16S rRNA	HFD vs. LFD:
				↑Hepatic lipid accumulation, ↑inflammatory cell infiltration, ↑leptin, ↑TNF-α
				↑Lactobacillus gasseri and/or ↑Lactobacillus taiwanensis
				Positive correlation of L. gasseri and/or L. taiwanensis DNA and lipid droplets in liver
Park et al., 2013 (57)	C57BL/6J mice	HFD + probiotic (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032) vs. HFD + placebo for 10 wk.	Sequencing 16S rRNA	HFD + probiotic vs. HFD + placebo:
				↓ALT, ↑FA oxidation–related genes, ↓proinflammatory genes (TNFa, IL6, IL1b), ↓gut microbiota diversity, ↑Bifidobacterium Pseudolongum
Pachikian et al., 2013 (58)	C57BL/6J mice	n–3 PUFA–depleted diet for 3 mo supplemented with FOSs during the last 10 d of treatment	DGGE, qPCR	n-3 PUFA-depleted diet supplemented with FOSs vs. n-3 PUFA-depleted diet:
				↑Bifidobacterium spp. ↓Roseburia spp., ↓SREBP2, ↑PPAR-α, ↓LDL, ↓HDL, ↑GLP-1
Cano et al., 2013 (59)	C57BL/6 mice	HFD supplemented with Bifidobacterium pseudocatenulatum CECT 7765 vs. HFD for 7 wk	qPCR	HFD supplemented with B. pseudocatenulatum CECT 7765 vs. HFD:
				↓Serum cholesterol, ↓serum TGs, ↓serum glucose, ↓insulin resistance, ↓hepatocytes with grade 3 steatosis, ↓fat absorption, ↓leptin, ↓IL-6, ↓MCP-1, ↑IL-4, ↑IL-10, ↑Bifidobacteria, ↓Enterobacteriaceae, ↓body weight gain, ↓food intake
Axling et al., 2012 (60)	C57BL/6J mice	HFD with or without a supplement GT and supplemented with Lp or the combination of both (Lp + GT) for 22 wk	Sequencing 16S rRNA, qPCR	Lp + GT vs. control:
				↑Lactobacillus, ↑diversity of bacteria, ↓liver weights, ↓liver size, ↓TGs, ↓ALT
				Akkermansia correlated negatively with body fat content (r = −0.43, P = 0.04), plasma insulin (r = −0.47, P = 0.03), and liver TGs (r = −0.44, P = 0.03).
Neyrinck et al., 2011 (61)	C57BL/6J mice	HFD supplemented with arabinoxylans from wheat vs. HFD for 4 wk	DGGE, qPCR	HFD supplemented with arabinoxylans from wheat vs. HFD:
				↑Bifidobacteria, ↓adipocyte size, ↓serum and hepatic cholesterol accumulation and insulin resistance, ↑tight junction proteins (ZO-1 and occludin), ↓inflammatory markers (IL-6 and MCP-1)
Cani et al., 2009 (62)	C57BL/6mice	Prebiotic (oligofructose) vs. nonprebiotic carbohydrates (microcrystalline cellulose) for 4 wk	DGGE, qPCR analysis	Prebiotic vs. nonprebiotic:
				↑Total bacteria count, ↑Lactobacillus spp., ↑Bifidobacterium spp., ↑Clostridium coccoides–Eubacterium rectale cluster, ↓LPS, ↑ZO-1 and occludin, ↓PAI-1, ↓NADPHox, ↓iNOS, ↓TLR4, ↓TNF-α, ↑GLP-2, ↓hepatic expression of inflammatory and oxidative stress markers
Cani et al., 2007 (33)	C57BL/6J mice	High-fat and carbohydrate-free diet vs. normal-diet group for 4 wk	FISH	High-fat and carbohydrate-free diet vs. normal-diet group:
				↑Liver weight, ↑Liver TGs, ↑TNF-α, ↑IL-1, ↑IL-6, ↑LPS, ↓Bifidobacterium spp., E. rectale/C. coccoides

¹ACC1, acetyl-CoA carboxylase 1; ALT, alanin transferase; BB-12, Bifidobacterium animalis subsp. lactis BB-12; ChREBP, transcription factor carbohydrate-responsive element-binding protein; DGGE, denaturing gradient gel electrophoresis; FAS, fatty acid synthase; FISH, Fuorescent in situ hybridization; FOS, fructo-oligosaccharide; GLP, glucagon-like peptide; GT, green tea powder; HF, high prebiotic fiber; HFD, high-fat diet; HP, high protein; iNOS, inducible nitric oxide synthase; LFD, low-fat diet; LGG, Lactobacillus rhamnosus GG; Lp, Lactobacillus plantarum DSM 15313; MCP-1, monocyte chemoattractant protein-1; NADPHox, NAD(P)H oxidase; NAFLD, nonalcoholic fatty liver disease; OFS, oligofructosaccharide; PAI-1, plasminogen activator inhibitor 1; PYY, peptide YY; ref, reference; rRNA, ribosomal RNA; SREBP2, sterol regulatory element binding protein 2; TLR4, Toll-like receptor 4; TNFa, tumor necrosis factor α (gene); ZO-1, zonula occludens-1; ↑, increased; ↓, decreased.