Table 2.
Short-chain fatty acids role in the recovery of impaired barrier function.
| SCFAs | Sample | Effect/Implicated mechanisms | References |
|---|---|---|---|
| In vitro | |||
| 10 or 100 mM mixed SCFA 10 or 100 mM acetic, propionic or butyric acids |
Ex vivo male Wistar rats Cecum and colon |
•Modulation contractile activity. | (40) |
| Butyrate and propionate | THP-1 cells | •Inhibition of TNF-α | (16) |
| Butyrate 2 mM [low] Butyrate 8 mM [high] |
Caco-2 cells | •[Low] promotion of intestinal barrier function, increase TEER and decrease inulin permeability. •[High] induce apoptosis, decrease cell viability. |
(41) |
| Mixed SCFA: acetate –propionate –butyrate 80:40:20, 40:20:10, and 20:10:5 (mmol/l) |
ex vivo colon Sprague-Dawley rats | •TEER: increase by physiological SCFA mixture and individual SCFA (dose-dependent). •Paracellular transport: dose-dependent reduced by mixed SCFA, acetate and propionate. |
(42) |
| 80 acetate, 40 propionate, and 20 butyrate (mmol/l) | Caco-2 cells | •TEER increase with acetate (40 and 80 mmol/l) and propionate (20 and 40 mmol/l). | |
| 80 acetate, 40 propionate, and 20 butyrate (mmol/l)Formate, lactate and succinate (50 mmol/l) | T84 cells | •Acetate + propionate: increase TEER dose/time-dependent manner. •Butyrate and formate do not change TEER. •Propionate, acetate and butyrate and lactate: TEER higher 30 min after (50 mmol/l). •Succinate reduces TEER. |
|
| Butyrate 2 mM | Caco-2 cells | •Increase AMPK activity. •Accelerated TJ assembly. •Increase TEER. |
(43) |
| Butyrate at 2, 5, or 8 mM SB203580: p38 MAPK inhibitor |
Caco-2 cells | •2 mM: does not modify intestinal permeability. •5- and 8-mM increase permeability. •5 mM + SB203580 restore the permeability. |
(44) |
| Butyrate, propionate, and acetate | YAMC and Caco-2 cells | •SCFA triggers Aryl hydrocarbon receptor-responsive genes. •AhR plays an important role in GI health and in the gut inflammation by the induction of Tregs. |
(45) |
| Acetate, propionate or butyrate with or without LPS | •Caco-2 cells | •Reduction NLRP3 inflammasome and autophagy. •Decrease intestinal barrier disruption. |
(46) |
| Main fecal SCFA (acetate, propionate and butyrate) |
ex vivo C57BL/6J mice | •Microbial SCFA are modulated by the circadian rhythm. SCFA affects colon contractility. |
(47) |
| Propionic acid (PA) | Intestinal epithelium cells (IEC-6) | •Promotion of cell migration. •Inhibition of NLRP3 inflammasome. •Activation and improvement of intestinal barrier function. •Suppression of TLR4/NF-κB pathway. |
(48) |
| SCFA produced by E. coli | Cancer cell lines: colon (HT-29), breast (MCF-7) and leukemia (THP-1) | •Lower cytotoxicity activity. •Decrease production of inflammatory cytokines. |
(49) |
| In vivo | |||
| Sodium butyrate | Wistar rat IBS model (WAS) |
•Dose-dependent inhibition of allodynia and colonic hyperpermeability. | (50) |
| GG and PHGG | DSS-induced colitis BALB/c mice | •Improved clinical score. •Up-regulation of colonic TJ. •High fecal SCFA |
(51) |
| Mixed SCFA: Sodium acetate (3 mM), Sodium propionate (1 mM), Sodium butyrate (1 mM) | Sprague-Dawley rat IBS model (WAS) |
•SCFA alleviated colonic spontaneous motility •Fecal SCFA reduction in WAS •Up-regulate SCFA colonic receptors in WAS. |
(52) |
| Acetate, propionate, and butyrate at 0.5, 1, 5, 10, 30 mM | Neonatal BALB/c mice-IBS model rectal 1% acetic ac. | •Dose-dependent reduction colonic transit rate. | (53) |
AhR, Aryl hydrocarbon receptor; AOS, Alginate oligosaccharide; CLDN, Claudin; DSS, Dextran Sulfate Sodium; GG, Guar gum; IBS, Irritable Bowel Syndrome; IL, Interleukin; LPS, Lipopolysaccharide; MUC, Mucin; NF-κB, Nuclear factor – kappa beta; NLRP3, NLR family pyrin domain containing 3; p-AMPKα, Phosphorylated AMP-activated protein kinase alpha; PHGG, Partially hydrolyzed GG; SCFA, short-chain fatty acid; TEER, Transepithelial electrical resistance; TJ, Tight junction; TLR, Toll-like receptor; TNF-α, Tumor necrosis factor alpha; Treg, Regulatory T lymphocyte; WAS, Water avoidance stress; YAMC, Young adult mouse colonic cells; ZO, Zonula occludens.