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

Sundaram, Tamil Selvi; Giromini, Carlotta; Rebucci, Raffaella; Pistl, Juraj; Bhide, Mangesh; Baldi, Antonella

doi:10.1186/s40104-022-00690-7

Journal of Animal Science and Biotechnology

Table 4 Effects of milk-derived exosomes 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	MDEs/MDE-miRNAs from	Immune response and morphological changes	Reference
In vitro
Porcine IPEC-J2 cells	Non-stimulated	Porcine milk	↑(Cell proliferation, CDX2, IGF-1R, PCNA, miRNAs targeting FAS, SERPINE and p53 pathways); ↓(FAS, SERPINE, p53)	[138]
Rat IEC-18 cells	Non-stimulated	Rat milk	↑(Cell viability, proliferation, PCNA, LGR5)	[145]
Human CCD841 cells or human LS123 cells	Non-stimulated	Human milk	↑(Cell proliferation, collagen type-I); ↓(twist1, PTEN) in CCD841 cells; = LS123 cells	[146]
Human LS174T cells	Non-stimulated	Bovine milk	↑(Mucin secretion, TFF3, MUC2, GRP94)	[147]
Human FHC cells	Mechanical wound	Human term or preterm milk	↑(Cell proliferation, migration and wound healing)	[38]
Porcine IPEC-J2 cells	LPS	Porcine milk	↑(Cell viability, IκBα); ↓(TLR4, MyD88, p-IκBα, p-NF-κB-p65, p-NF-κB, NF-κB nuclear translocation, Tp53, FAS, Caspase-3, IL-1β, IL-6, TNF-α)	[148]
Porcine IPEC-J2 cells	LPS	Porcine milk	↑(Cell viability, IκBα); ↓(TLR4, p-IκBα, p-NF-κB-p65, p-NF-κB, NF-κB, Tp53, p53, FAS, Caspase-3, IL-1β, IL-6, TNF-α)	[149]
Porcine IPEC-J2 cells	DON	Porcine milk	↑(Cell viability, proliferation, β-catenin, CCND1, Akt, ZO-1, OCLN, CLDN1, PCNA, miRNAs targeting p53 pathway); ↓(Tp53, FAS, SERPINE1, p21)	[150]
Rat IEC-6 cells	Hypoxia	Yak milk	↑(Cell viability, proliferation, PHD-1); ↓(HIF-1α, VEGF, p53)	[151]
Rat IEC-6 cells	Hypoxia	Yak milk	↑(Cell viability, Ki67⁺ cells, PHD-1); ↓(HIF-α, VEGFA, p53, Bax, caspase-3/-9)	[39]
Rat IEC-6 cells or human FHS-74 cells	Hypoxia/reoxygenation	Human milk	↑(Living cell count, proliferation); ↓apoptosis	[152]
Rat IEC-6 cells	H₂O₂	Bovine milk	↑(Cell viability, superperoxide dismutase, glutathione peroxidase); ↓(ROS, LDH, malondialdehyde, NRF2, HO-1)	[153]
Neonate mice intestinal organoids	LPS	Human colostrum, transitional or matured milk	↓(Structural damage, TNF-α, TLR4, LGR5, Ki67)	[154]
Neonate mice intestinal organoids	Hypoxia and LPS	Human raw or pasteurized milk	↓(Structural damage, IL-6, MPO); ↑(MUC2, goblet cell abundance)	[155]
In vivo
Mice	Non-stimulated	Porcine milk	↑(Small intestinal V/C ratio, CDX2, PCNA, IGF-1R); ↓p53	[138]
Mice	Non-stimulated	Bovine milk	↑(MUC2, RegIIIγ, MyD88, GATA4, IgA, secretory IgA, enterocyte abundance, V/C, cecum surface area)	[156]
Mice	LPS	Porcine milk	↓(IL-1β, IL-6, TNF-α); ↑(jejunum morphology, villi structure, V/C ratio)	[148]
Mice	DON-colitis	Porcine milk	↓(p53, p21, caspase-3/-9, villi damage); ↑(jejunum villus height, crypt depth, V/C ratio, intestinal length, β-catenin, CCND1, phospho-Akt, ZO-1, OCLN, CLDN1, miRNAs targeting p53 pathway)	[150]
Mice	DSS-colitis	Human milk	↑(TGF-β1, miRNAs targeting DNMT1/DNMT3); ↓(colon shortening, inflammatory cell infiltration, tissue damage, lesions, DNMT1/DNMT3, IL-6, TNF-α)	[157]
Transgenic mice	Tamoxifen-ulcerative colitis	Bovine milk	↑(Colon length and weight); ↓mucosal injury	[158]
Neonate rats	Formula feeding and hypoxia-induced NEC	Human preterm milk	↑(Villus integrity, enterocyte proliferation); ↑(peptides promoting epithelial proliferation, migration, regeneration and immunomodulation)	[38]
Neonate mice	Formula feeding, LPS and hypoxia-induced NEC	Bovine milk	↓(Intestinal damage, MPO); ↑(MUC2⁺/GRP94⁺ goblet cell abundance)	[147]
Neonate mice	Formula feeding, LPS and hypoxia-induced NEC	Human milk	↓(Intestinal damage, severity and incidence of disease)	[152]
Neonate mice	Formula feeding, LPS and hypoxia-induced NEC	Human raw or pasteurized milk	↑(Goblet/MUC2⁺ cell abundance);↓(MPO, IL-6, mucosal injury)	[155]

The arrow indicates an increase (↑) or decrease (↓) in the level or activity of the different parameters analysed, “=” symbol designates unchanged parameters. Akt Protein kinase B, Bax B-cell lymphoma 2-associated X protein, CCND1 Cyclin D1, CDX2 Homeobox transcription factor-2, CLDN Claudin, DNMT DNA methyltransferase, DON Deoxynivalenol, DSS Dextran sulphate sodium, FAS Cell surface death receptor, GATA4 GATA binding protein 4, GRP94 Glucose-regulated protein-94, HIF-1α Hypoxia-inducible factor-1α, HO-1 Heme oxygenase-1, H₂O₂ Hydrogen peroxide, Ig Immunoglobulin, IGF-1R Insulin-like growth factor 1 receptor, IL Interleukin, Ki67 Cell proliferation marker, LDH Lactate dehydrogenase, LGR5 Leucine-rich repeat-containing G-protein coupled receptor 5, LPS Lipopolysaccharides, miRNA microRNA, MPO Myeloperoxidase, MUC2 Mucin 2, MyD88 Myeloid differentiation primary response 88, NF-κB Nuclear factor-κB, NEC Necrotizing enterocolitis, NRF Nuclear factor erythroid 2-related factor, OCLN Occludin, PCNA Proliferating cell nuclear antigen, PHD-1 Prolyl hydroxylases-1, p-IκBα phospho-Nuclear factor-κB inhibitor α, p-NF-κB phospho-Nuclear factor-κB, p-NF-κB-p65 phospho-Nuclear factor-κB p65 subunit, PTEN Phosphatase and tensin homolog, Ki67 Cell proliferation marker, RegIIIγ Regenerating islet-derived protein 3 gamma, ROS Reactive oxygen species, SERPINE Serine protease inhibitor clade E, TGF Transforming growth factor, TFF3 Trefoil factor family-3, TLR Toll-like receptor, TNF Tumour necrosis factor, Tp53 or p53 Tumour protein 53, V/C Villus height/crypt depth, VEGFA Vascular endothelial growth factor-A, ZO Zonula occludens

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ISSN: 2049-1891

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