Table 3.
Impact of SCFAs on intestinal homeostasis.
Cell type | Model | SCFAs | Effect | Mechanism | References | |
---|---|---|---|---|---|---|
Epithelial cells | Cell lines | Caco-2 | Butyrate 2 mM | ↑ TEER, ZO-1, occludin | Activation of AMPK Inhibition of MLCK/MLC2 pathway and phosphorylationof PKCβ2 | (77, 78) |
Butyrate 5 mM | ↑ TEER, claudin-7, claudin-2 | Not determined | (79) | |||
Caco-2, T84 | Butyrate 5 mM Propionate 20 mM | ↑ TEER, ↓ Claudin-2 |
Induction of IL-10RA through STAT3 activation and HDAC inhibition | (80) | ||
Cdx2-IEC | Butyrate 4 mM | ↑ TEER, claudin-1, ZO-1, occludin | Induction of Claudin-1 transcription through SP1 | (81) | ||
IPEC-J2 | Butyrate 1 mM | ↓ LPS impairment of intestinal barrier ↑ Claudin 3 and claudin 4 |
Activation of Akt/mTOR signaling | (82) | ||
CCD841, KM12L4, and HCT116 | Butyrate 1 mM | Blockade of LPS-induced NF-κB | Activation of GPR109A | (66) | ||
Primary cells | Colon culture | Butyrate 0.5 mM | ↑ IL-18 mRNA and protein | Activation of GPR109A | (68) | |
Mouse small intestine organoids | Acetate, propionate and butyrate 5 mM | ↑Fiaf, Hdac3, Hdac5 ↓ Gpr43, Pparγ |
Not determined | (70) | ||
Acetate, propionate and butyrate 0.5 mM | ↑Promotion of organoids development | Activation of GPR41 or GPR43 and MEK-ERK signaling | (69) | |||
Immune cells | Cell lines | RAW 264.7 | Sodium butyrate (NaB), sodium phenylbutyrate (NaPB) and sodium phenylacetate (NaPA) 0.5–1 mM | ↑ IL-10 ↓ IFN-γ-induced iNOS, TNF-α, IL-6 |
Inhibition of NF-κB and ERK signaling pathways | (83) |
Primary cells | Human LP macrophages | Butyrate enemas 100 mM | ↓ Inhibition of NF-κB translocation | Not determined | (84) | |
Human monocytes | Acetate, propionate and butyrate 0.2–20 mM | ↑ PGE2 ↓ MCP-1, IL-10 |
Activation of PTX-sensitive GPCRs | (61) | ||
PBMC | Acetate, propionate and butyrate 0.2–20 mM | ↓ LPS-induced TNF-α and IFN-γ | Not determined | |||
Human monocyte-derived DCs | Propionate and butyrate 1 mM | ↓ LPS-induced chemokines and cytokines (CXCL9-CXCL11), cytokines (IL-6 and IL-12p40) | Not determined | (62) | ||
Mouse LP macrophages and BMDM | Butyrate 0.1–2 mM | ↓ LPS-induced mediators NO, IL-6, IL-12p40 | Inhibition of HDACs | (67) | ||
Mouse DCs | Butyrate 0.125–2 mM | ↑ Foxp3+CD4+ T cells | Inhibition of HDACs | (85) | ||
Mouse LP macrophages and DCs | Butyrate 0.5 mM | ↑ Foxp3+CD4+ T cells | Activation of GPR109A | (68) | ||
Mouse T cells | Propionate butyrate 0.1 mM | ↑ Foxp3 and IL-10 in naïve CD4+ T cells | Activation of GPR43 and Inhibition of HDACs | (64, 86) |