Table 4.

The studies on two-sided role of SCFA in host health via “gut-liver axis” establishing the connection between gut and liver.

Item	Model/subject	Administration route	Dose and duration	Outcomes	Effects type	Reference
Butyrate	C57BL/6J mice NAFLD model	Gavage	Sodium butyrate (0.12 g/mL), 6 weeks	↓ NASH development, which may be driven by the protective gut microbiome and metabolome	Beneficial effect	Ye et al. (2018)
SCFA	Male C57BL/6J mice, PPAR lox/lox mice, 2 months of age	Dietary intake	Acetate, propionate or butyrate was incorporated into diet at 5% (wt/wt)	↓ PPARγ expression in the liver; ↓ hepatic triglyceride concentrations	Beneficial effect	den Besten et al. (2015)
Butyrate	C57BL/6J mice NAFLD model, liquid as control	Oral consumption	Sodium butyrate (0.6 g/kg body weight per day), 6 weeks	↓ Inflammation in the liver; ↓ development of NASH	Beneficial effect	Jin et al. (2015)
Acetate	Male wistar rats, water as control	Oral gavage	Sodium acetate (200 mg/kg), 8 weeks	↓ Xanthine oxidase activity, and performs hepatoprotection	Beneficial effect	Dangana et al. (2020)
Acetate	Hyla rabbits, saline as control	Subcutaneous injection	Acetate (2 g/kg body weight per day, one injection each day), 4 days	↓ Intramuscular triglyceride level; ↑ fatty acid uptake; ↑ fatty acid oxidation	Beneficial effect	Liu et al., 2019b, Liu et al., 2019a
SCFA	Thirteen overweight and obese, 20–50 years old Caucasian men	Rectal infusion	SCFA mixtures (acetate, propionate and butyrate), 4 clinical investigation days	↑ Fat oxidation, energy expenditure and PYY; ↓ lipolysis in overweight/obese men	Beneficial effect	Araujo et al. (2020)
Propionate	Human HepG2 hepatocytes	Following propionate treatment of the cells for 24 h	Propionate (0, 0.25, 0.5 mM) for HepG2 cells)	↓ Gene expression of gluconeogenic enzymes independent of insulin signaling	Beneficial effect	Yoshida et al. (2019)
Propionate, butyrate	Duroc × Landrace × Yorkshire pigs (50% male) weaned at day 28	Dietary intake	Basal diet plus 1 g propionate/kg, or plus 1 g butyrate/kg diet for 14 d	↑ Serum PYY concentration; ↑ lipid metabolism	Beneficial effect
SCFA	Multi-organ model of UC ex vivo	–	20 mM of SCFA	↑ Effector function of activated CD4+ T cells; ↓ acute CD4+ T cell-dependent UC inflammation; ↑ risk of liver injury	Pathological effect	Trapecar et al. (2020)
Butyrate	Primiparous purebred female SD rats	Dietary intake	1% sodium butyrate diet	↑ Promotes maternal fat mobilization, ↑ fatty acid uptake and lipid accumulation in the liver of offspring	Pathological effect	Zhou et al. (2016)

NAFLD = nonalcoholic fatty liver disease; NASH = non-alcoholic hepatitis; SCFA = short chain fatty acids; PPAR = peroxisome proliferator-activated receptor; PYY = peptide YY; UC = ulcerative colitis. ↑ represents increase. ↓ represents decrease.