Identification of omega-3 oxylipins in human milk-derived extracellular vesicles with pro-resolutive actions in gastrointestinal inflammation.

Data de publicació: 20/11/2023 Data Ahead of Print: 20/11/2023

Autors de IIS La Fe

Marta Gómez Ferrer

Autor
Elena Amaro Prellezo

Autor
Abel Albiach Delgado

Autor
Isabel Ten Doménech

Autor
Julia Kuligowski

Autor
Pilar Sepúlveda Sanchis

Autor

Grups d'Investigació

Perinatología

Leader

Máximo Vento Torres
Regeneración y Trasplante Cardíaco

Leader

Pilar Sepúlveda Sanchis

Abstract

INTRODUCTION: Premature infants (PIs) are at risk of suffering necrotizing enterocolitis (NEC), and infants consuming human milk (HM) show a lower incidence than infants receiving formula. The composition of HM has been studied in depth, but the lipid content of HM-derived small extracellular vesicles (HM sEVs) remains unexplored. Identifying these molecules and their biological effects has potential for the treatment of intestinal disorders in PIs and could contribute to the development of HM-based fortified formulas. METHODS: We isolated HM sEVs from HM samples and analyzed their oxylipin content using liquid chromatography coupled to mass spectrometry, which revealed the presence of anti-inflammatory oxylipins. We then examined the efficacy of a mixture of these oxylipins in combating inflammation and fibrosis, in vitro and in a murine model of inflammatory bowel disease (IBD). RESULTS: HM-related sEVs contained higher concentrations of oxylipins derived from docosahexaenoic acid, an omega-3 fatty acid. Three anti-inflammatory oxylipins, 14-HDHA, 17-HDHA, and 19,20-DiHDPA (?3 OXLP), demonstrated similar efficacy to HM sEVs in preventing cell injury, inducing re-epithelialization, mitigating fibrosis, and modulating immune responses. Both ?3 OXLP and HM sEVs effectively reduced inflammation in IBD-model mice, preventing colon shortening, infiltration of inflammatory cells and tissue fibrosis. DISCUSSION: Incorporating this unique cocktail of oxylipins into fortified milk formulas might reduce the risk of NEC in PIs and also provide immunological and neurodevelopmental support.

Dades de la publicació

ISSN/ISSNe:: 1664-3224, 1664-3224
Tipus:: Article
Pàgines:: 1293737-1293737
DOI:: 10.3389/fimmu.2023.1293737
PubMed:: 38054009
Factor d'Impacte:: 2,331 SCImago ℠
Quartil:: Q1 SCImago ℠

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Mètriques

Filiacions

Gómez-Ferrer M:: Regenerative Medicine and Heart Transplantation Unit, Health Research Institute Hospital La Fe, Valencia, Spain
Amaro-Prellezo E:: Regenerative Medicine and Heart Transplantation Unit, Health Research Institute Hospital La Fe, Valencia, Spain
Albiach-Delgado A:: Instituto de Investigación. Neonatal Research Group, Health Research Institute Hospital La Fe, Valencia, Spain
Ten-Domenech I:: Instituto de Investigación. Neonatal Research Group, Health Research Institute Hospital La Fe, Valencia, Spain
Kuligowski J:: Instituto de Investigación. Neonatal Research Group, Health Research Institute Hospital La Fe, Valencia, Spain
Sepúlveda P:: Regenerative Medicine and Heart Transplantation Unit, Health Research Institute Hospital La Fe, Valencia, Spain

Cardiology Service, Hospital Universitari i Politècnic La Fe, Valencia, Spain

Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Carlos III Institute of Health, Madrid, Spain

Department of Pathology, University of Valencia, Valencia, Spain

Keywords

human milk (HM); inflammatory bowel disease (IBD); necrotizing enterocolitis (NEC); oxylipins; small extracellular vesicles (sEVs)

Projectes associats

CREACION Y MEJORA DE INFRAESTRUCTURAS EN MEDICINA REGENERATIVA

Investigador Principal: FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA

PLE2009-0141 ACI-PLAN E . MINISTERIO DE CIENCIA E INNOVACION; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009