Table 5.
The studies on two-sided role of SCFA in host health via “gut-lung axis” establishing the connection between gut and lung.
| Item | Model/subject | Administration route | Dose and duration | Outcomes | Effects type | Reference |
|---|---|---|---|---|---|---|
| SCFA | Sputum samples from cystic fibrosis patients, A549, CFBE, corrCFBE or primary human bronchial epithelial cells | Cells incubated for 1 h with various SCFA prior to cytomix stimulation | SCFA: colonic lumen (10-50 mM) cystic fibrosis airways (0.1-5 mM) | ↓ Airway epithelium inflammatory responses, ↑iNOS and Pseudomonas aeruginosa growth | Beneficial effect | Ghorbani et al. (2015) |
| Butyrate | Adult female mice fed a low-fiber diet for 4 weeks then received butyrate | Oral gavage | Sodium butyrate (500 mM) for 2 weeks | Balancing innate and adaptive immunity; ↓ influenza infection; ↓ immune-associated pathology | Beneficial effect | Trompette et al. (2018) |
| SCFA | Differentiating human bronchial epithelial cells (16HBE) | 16HBE cells were stimulated with IL-4, IL-13 or house dust mite, then with SCFA | 10 mM acetate, 0.5 mM propionate or 1 mM butyrate | ↑ Lung immune defense effects; ↑ tight junction proteins expression in the airway epithelial barrier | Beneficial effect | Richards et al. (2021) |
| SCFA | Female C57BL/6 mice cigarette smoking-exposed emphysema model | Mice with standard AIN 76A diet, high-cellulose and high-pectin diet | – | ↓ Emphysema development; ↓ local and systemic inflammation | Beneficial effect | Jang et al. (2021) |
| Butyrate | Sprague–Dawley rat model of hypoxic pH, rat microvascular endothelial cells | SD rat: oral gavage; cells: cells were pretreated with butyrate for either 2 or 24 h, followed by either LPS or TNF-α stimulation |
SD rat: butyrate (220 and 2200 mg/kg intake); cells: butyrate (1 mM) | ↓ Accumulation of CD68+ in the lung alveoli; ↓ CD68+ and CD163+ pulmonary macrophages in lung interstitial | Beneficial effect | Karoor et al. (2021) |
| SCFA | C57BL/6 female mice treated with different fiber content diet | Oral gavage in drinking water before exposed to house dust mite extract | Sodium acetate or sodium propionate (200 mM) for 3 weeks | Shape the immunological environment in the lung; ↓ severity of allergic inflammation | Beneficial effect | Trompette et al. (2014) |
| SCFA | Vancomycin-treated mice, autoclaved water as control | Oral gavage | 40 mM butyrate, 67.5 mM acetate plus 25.9 mM propionate | ↓ Th2 responses to modulate the systemic immune response | Beneficial effect | Cait et al. (2018) |
| SCFA | Primary HLF and ASM cells with TNF-α (1 ng/mL) | Cells stimulated with SCFA for 24 or 96 h, with or without TNF-α for another 12 or 24 h | Acetate (0.5-25 mM), propionate (0.5-25 mM), butyrate (0.01-10 mM) | ↑ TNF-α-induced inflammatory responses; ↑ IL-6 and C-X-C motif chemokine ligand 8 release via activation of FFAR3 and p38 MAPK signaling | Pathological effect | Rufting et al. (2019) |
| SCFA | Peripheral blood mononuclear cells or neutrophils | Cells stimulated with LPS alone or in combination with various SCFA | SCFA (0-20 mM) for 18 h | ↑ Pro-inflammatory milieu in the lower genital tract | Pathological effect | Mirmonsef et al. (2012) |
SCFA = short chain fatty acids; iNOS = inducible nitric oxide synthase; IL-4 = interleukin-4; IL-13 = interleukin-13; LPS = lipopolysaccharide; TNF-α = tumor necrosis factor-α; HLF = human lung fibroblasts; IL-6 = interleukin-6; ASM = airway smooth muscle; FFAR3 = free fatty acid receptor 3; MAPK = mitogen-activated protein kinase kinases; LPS = lipopolysaccharides. ↑ represents increase. ↓ represents decrease.