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Table 1 Effects of omega-3 polyunsaturated fatty acids in the intestinal cell and animal models

From: Role of omega-3 polyunsaturated fatty acids, citrus pectin, and milk-derived exosomes on intestinal barrier integrity and immunity in animals

Model of study

Stress by

ω-3 PUFA(s) assessed

Immune response and morphological changes

Reference

In vitro

 Human Caco-2 cells

Non-stimulated

EPA

(↓HRP flux, =TEER) at 100 μmol/L PUFA for 24 h; ↑LDH release > 100 μmol/L PUFA for 48 h

[56]

 Human Caco-2 cells

Non-stimulated

ALA or EPA

(↑FS flux, ↓TEER) until 200 μmol/L PUFA; ↑LDH release for 200 μmol/L PUFA

[57]

 Human T84 cells

IL-4

ALA, EPA or DHA

(↑TEER, ↓FD4 flux) for 100 μmol/L PUFA

[58]

 Human Caco-2 cells

Heat injury

EPA or DHA

↑(TEER, ZO-1, OCLN, CLDN-2); ↓HRP flux

[59]

 Rat IEC-6 cells

Mechanical wound

ALA, EPA, DHA or Docosapentaenoic acid

↑(TGF-β1, cell proliferation and migration in wound healing); ↓PGE2

[60, 61]

 Human Caco-2 cells

IL-1β

ALA, EPA or DHA

↓(IL-6, IL-8, iNOS); ↑PPARγ; =IκB

[62]

 Human Caco-2 cells

IL-1β

ALA or fish oil

↓(COX-2, IL-8, iNOS)

[63]

 Human Caco-2 cells, human NCM460 cells, fetal H4 cells or neonate NEC-IEC cells

IL-1β

EPA or DHA

↓(NF-κβ1, IL-8, IL-6, IL-1R1)

[64]

 Porcine IPEC-1 cells

DON

EPA or DHA

↑(Cell proliferation, viability, LDH release) until 25 μg/mL PUFA; ↑(TEER, CLDN-1, ZO-1) at 12.5 μg/mL PUFA; ↓(FD4 flux, caspase-3/-8, necrotic cells, ROS TNFR1, RIPK-1/-3, MLKL, PGAM5, DRP1, HMGB1) at 12.5 μg/mL PUFA

[65]

 Porcine IPEC-J2 cells

LPS, DSS or H2O2

EPA or DHA

↑(Cell proliferation, viability); ↓(LDH release, caspase-3/-7); =NO2

[66]

 Pig ileum explants

LPS

Fish oil

↓LPS permeability; =TEER

[67]

In vivo

 Rat

Acetic acid-colitis

ω-3 PUFA-rich lipid emulsion

↓(PGE2, LTB4, TXB2, macrophage infiltration, mucosal and tissue damage); =LTC4

[68]

 Rat

TNBS-colitis

ALA

↓(ICAM-1, VCAM-1, VEGFR-2); =HO-1

[69]

 Rat

TNBS-colitis

Fish oil

↓(COX-2, PGE2, LTB4, NF-κB); =(TNF-α, IL-1β, PPARγ, mucosal damage, inflammatory cell infiltration)

[70]

 Rat

DSS-colitis

Fish oil

↓(Disease activity, colon weight/length ratio, mucosal ulceration, crypt dilation, goblet cell depletion, inflammatory cell infiltration, tissue damage, MPO, iNOS, AP, COX-2, LTB4, TNF-α); ↑glutathione; =IL-1β

[71]

 Rat

DSS-colitis

MaR1

↓(Disease activity, colon shortening, mucosal damage, inflammatory cell infiltration, PGE2, MPO, ROS, TLR4, p-NF-κB-p65, TNF-α, IL-6, IL-1β); ↑(ZO-1, OCLN, NRF2, HO-1)

[72]

 Neonate rats

Hypoxia and formula feed-induced NEC

DHA

↓(TLR2/4, PAFR, tissue necrosis, incidence of disease); =phospholipase A2-II in small and/or large intestine

[73]

 Maternal rats

Formula feed-induced NEC

EPA or DHA

↑(PGE2 receptor EP3, PGD2 receptor DP2, PPARγ) and ↓(IκBα/β, mucosal damage, inflammatory cell infiltration, incidence of disease) in premature rat pups

[74]

 Mice

Acute or chronic

DSS-colitis

MaR1

↓(Disease activity, MPO, NF-κB, IL-1β, IL-6, TNF-α, INFγ, ICAM-1, crypt damage, inflammatory cell infiltration, colon wall thickness, colon shortening, hyperaemia and tissue damage)

[75]

 Peritonitis mice

TNBS-colitis

RvE1

↑Tissue repair; ↓(leukocyte infiltration, COX-2, TNF-α, IL-12p40, iNOS, MPO); =(INF-γ, IL-4, IL-10, TGF-β)

[76]

 Mice

Citrobacter rodentium

Fish oil

↑IL-10; ↓(mucosal damage, inflammatory cell infiltration, apoptotic cells, Ki67+ enterocytes, MIP-2, keratinocyte cytokine, MCP-1, IFN-γ, IL-6, IL-17A, FD4 intestinal permeability); =(mucosal adherent pathogen count, TNF-α, TGF-β, FoxP3)

[77]

 Mice

LPS

Fish oil

↓(COX-2, TLR4, MyD88, NF-κB, IL-1β, IL-6, TNF-α); =(iNOS, MCP-1, IL6, TNF-α) in small intestine

[78]

 Mice

LPS

EPA or DHA

↑(E-cadherin, ZO-1, OCLN, GPR120, FFAR-2, MUC2, IL-10, tissue repair); ↓(NF-κB-p65, TAK1, INFγ, TNF-α, IL-1β, IL-6); =(TLR4, jejunum villus hight, crypt depth, V/C ratio)

[79]

 Pigs

Non-stimulated

Fish oil

↓(PGE, PGI2, TXB2, crypt depth); =(colonic mucosal morphology)

[80]

 Sows

Non-stimulated

Linseed oil

↓(δ-5/-6 desaturase, HRP flux until d 28, villus height at d 0, crypt depth at d 7) in piglet ileum; =ileum enterocyte maturation in piglets

[81]

 Sows

Non-stimulated

Extruded linseed

↑(FD4/LPS permeability between d 0–28 in piglet jejunum explant); =(FD4/LPS permeability at d 52, IL-8, TNF-α in LPS-challenged piglet jejunum explants)

[82]

 Weaned piglets

LPS

Fish oil

↑(Villus height, V/C ratio, OCLN, CLDN-1); ↓(diamine oxidase, TNF-α, PGE2, caspase-3, HSP70, NF-κB-p65, TLR4, MyD88, IRAK1, TRAF6, NOD2, RIPK-2); =(NF-κB-p65, NOD1, crypt depth) in jejunum and/or ileum

[83]

 Weaned piglets

DSS-colitis

Fish oil

↑(Mitotic figures in enterocytes, UPC3, disease remission); =(mucosal damage, PPARγ, PGC1-α, TNF-α, KGF)

[84]

 Suckling piglets

Ischemia-injured ileum

EPA

↓PGE2; ↑(TEER, H3-mannitol/C14-inulin flux, COX-2); =mucosal damage

[85]

  1. The arrow indicates an increase (↑) or decrease (↓) in the level or activity of the different parameters analysed, “=” symbol designates unchanged parameters. ALA Alpha-linolenic acid, AP Alkaline phosphatase, COX Cyclooxygenase, DHA Docosahexaenoic acid; DON: Deoxynivalenol; DRP1: Dynamin-related protein 1, DSS Dextran sulphate sodium, 17,18-EEP 17,18-Epoxyeicosatetraenoic acid, EPA Eicosapentaenoic acid, FD4 Fluorescein isothiocyanate-labelled dextran 4 kDa, FFAR-2 Free fatty acid receptor-2, FS Fluorescein sulfonic acid, 5-FU 5-Fluorouracil, GPR G-protein coupled receptor, HMGB1 High mobility group box-1 protein, HO-1 Heme oxygenase-1, H2O2 Hydrogen peroxide, HRP Horseradish peroxidase, HSP70 Heat shock protein-70, IκB Inhibitor of nuclear factor kappa B, ICAM-1 Intercellular adhesion molecule-1, IEC Intestinal epithelial cells, IL Interleukin, INFγ Interferon γ, iNOS Inducible nitric oxide synthase, IRAK1 Interleukin-1 receptor-associated kinase-1, 8-Iso PGF3α 8-Iso prostaglandin F3α, KGF Keratinocyte growth factor, LDH Lactate dehydrogenase, LPS Lipopolysaccharides, LT Leukotriene, MaR Maresin, MCP-1 Monocyte chemoattractant protein-1, MIP-2 Macrophage inflammatory protein-2, MLKL Phosphorylated mixed lineage kinase-like protein, MPO Myeloperoxidase, MUC Mucin, MyD88 Myeloid differentiation primary response 88, NEC Necrotizing enterocolitis, NF-κB Nuclear factor-κB, NO2−/NO3 Nitrite/nitrate, NOD Nucleotide-binding oligomerization domain-containing protein, NRF2 Nuclear factor erythroid 2-related factor 2, OCLN Occludin, PAFR Platelet-activating factor receptor, PGAM5 Phosphoglycerate mutase family 5, PG Prostaglandin, PGC1-α PPARγ co-activator 1-α, PPAR Peroxisome proliferator-activated receptor, PUFA Polyunsaturated fatty acid, RIPK Receptor-interacting protein kinase, ROS Reactive oxygen species, RvE E-series resolvin, TAK1 Transforming growth factor-β-activated kinase 1, TEER transepithelial electrical resistance, TGF Transforming growth factor, TNBS 2,4,6-trinitrobenzene sulfonic acid, TNF Tumour necrosis factor, TNFR1 Tumour necrosis factor receptor-1, TRAF6 Tumour Necrosis Factor Receptor-Associated Factor-6, TXB Thromboxane, UPC3 PPARγ-responsive gene uncoupling protein-3, V/C Villus height/crypt depth, VCAM-1 Vascular adhesion molecule-1, VEGFR-2 Vascular endothelial growth factor-2, ZO Zonula occludens