Modulation of the Intestinal Barrier Integrity and Repair by Microbiota Extracellular Vesicles through the Differential Regulation of Trefoil Factor 3 in LS174T Goblet Cells

Yenifer Olivo-Martínez; Manel Bosch; Josefa Badia; Laura Baldomà

doi:10.3390/nu15112437

journal article Open Access May 24, 2023

Modulation of the Intestinal Barrier Integrity and Repair by Microbiota Extracellular Vesicles through the Differential Regulation of Trefoil Factor 3 in LS174T Goblet Cells

Yenifer Olivo-Martínez Manel Bosch

Josefa Badia

Laura Baldomà

Nutrients Vol. 15 No. 11 pp. 2437 · MDPI AG

View at Publisher Save 10.3390/nu15112437

Abstract

Trefoil factor 3 (TFF3) plays a key role in the maintenance and repair of intestinal mucosa. TFF3 expression is upregulated by the microbiota through TLR2. At the posttranscriptional level, TFF3 is downregulated by miR-7-5p. Reduced TFF3 levels have been detected in the damaged tissue of IBD patients. Here, we investigate the regulation of TFF3 expression by microbiota extracellular vesicles (EVs) in LS174T goblet cells using RT-qPCR and inhibitors of the TLR2 or PI3K pathways. To evaluate the subsequent impact on epithelial barrier function, conditioned media from control and vesicle-stimulated LS174T cells were used to treat Caco-2 monolayers. The barrier-strengthening effects were evaluated by analysing the expression and subcellular distribution of tight junction proteins, and the repairing effects were assessed using wound-healing assays. The results showed a differential regulation of TFF3 in LS174T via EVs from the probiotic EcN and the commensal ECOR12. EcN EVs activated the TFF3 production through TLR2 and downregulated miR7-5-p through PI3K. Consistently, high levels of secreted TFF3 reinforced the tight junctions and stimulated wound healing in the Caco-2 cells. ECOR12 EVs did not cause these effects. TFF3 is a potential therapeutic target in IBD. This study contributes to understanding the molecular players (microbiota EVs) connecting gut microbes to health and may help in designing better nutritional interventions based on microbiota bioactive compounds.

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Published: May 24, 2023
Vol/Issue: 15(11)
Pages: 2437
License: View

Authors

Y

Yenifer Olivo-Martínez

Secció de Bioquímica i Biologia Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), 08028 Barcelona, Spain; Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain

M

Manel Bosch

Unitat de Microscòpia Òptica Avançada, Centres Científics i Tecnològics, Universitat de Barcelona, 08028 Barcelona, Spain

J

Josefa Badia

Secció de Bioquímica i Biologia Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), 08028 Barcelona, Spain; Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain

L

Laura Baldomà

Secció de Bioquímica i Biologia Molecular, Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona, 08028 Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), 08028 Barcelona, Spain; Institut de Recerca Sant Joan de Déu (IRSJD), 08950 Barcelona, Spain

Funding

Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación, España Award: PID2019-107327RB-100

Cite This Article

Yenifer Olivo-Martínez, Manel Bosch, Josefa Badia, et al. (2023). Modulation of the Intestinal Barrier Integrity and Repair by Microbiota Extracellular Vesicles through the Differential Regulation of Trefoil Factor 3 in LS174T Goblet Cells. Nutrients, 15(11), 2437. https://doi.org/10.3390/nu15112437

Modulation of the Intestinal Barrier Integrity and Repair by Microbiota Extracellular Vesicles through the Differential Regulation of Trefoil Factor 3 in LS174T Goblet Cells

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