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Cells
Volume 14
Issue 18
10.3390/cells14181432
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Multi-Strain Probiotic Lysate Attenuates TGF-β1-Induced Intestinal Fibrosis and EMT Modulating Smad, Akt, and WNT/β-Catenin Pathways

by
Alessia Ciafarone
1,
Serena Artone
1,
Valeria Ciummo
2,
Francesca Rosaria Augello
1,
Serena Altamura
1,
Francesca Lombardi
1,
Giovanni Latella
1,
Paola Palumbo
1,† and
Benedetta Cinque
1,*,†
1
Department of Life, Health & Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
2
Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio”, 66100 Chieti, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2025, 14(18), 1432; https://doi.org/10.3390/cells14181432
Submission received: 1 August 2025 / Revised: 4 September 2025 / Accepted: 10 September 2025 / Published: 12 September 2025
(This article belongs to the Special Issue Fibrosis in Chronic Inflammatory Diseases)
Versions Notes

Abstract

Intestinal fibrosis is a common complication of inflammatory bowel diseases (IBD), and, to date, effective and safe antifibrotic drugs are still lacking. Emerging evidence suggests that probiotics may provide novel strategies to counteract fibrotic processes. In this study, we evaluated the anti-fibrotic potential of a multi-strain probiotic formulation, OxxySlabTM, using in vitro models of intestinal fibrosis and epithelial-to-mesenchymal transition (EMT). Human intestinal fibroblasts (CCD-18Co cell line) and epithelial cells (Caco-2 cell line, IECs) were stimulated with transforming growth factor-β1 (TGF-β1) to induce fibrotic and EMT phenotypes, respectively. Treatment with OxxySlab modulated cell proliferation and fibrosis-related markers, which we assessed through CCK-8 assay, Western blotting, and immunofluorescence. The probiotic lysate inhibited both canonical and non-canonical TGF-β1 signaling pathways, and it also reduced TGF-β1 gene expression in activated myofibroblasts, as shown by RT-qPCR. Furthermore, probiotic treatment reversed EMT features by restoring epithelial markers and downregulating mesenchymal markers. These findings highlight the beneficial effects of the multi-strain probiotic formulation as an adjunctive therapeutic agent targeting key pathways involved in intestinal fibrosis.
Keywords: intestinal fibrosis; fibroblast-to-myofibroblast transition; epithelial-to-mesenchymal transition (EMT); multi-strain probiotics; fibrotic signaling pathway; TGF-β1 signaling; intestinal fibroblasts; intestinal epithelial cells; inflammatory bowel disease (IBD) intestinal fibrosis; fibroblast-to-myofibroblast transition; epithelial-to-mesenchymal transition (EMT); multi-strain probiotics; fibrotic signaling pathway; TGF-β1 signaling; intestinal fibroblasts; intestinal epithelial cells; inflammatory bowel disease (IBD)

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MDPI and ACS Style

Ciafarone, A.; Artone, S.; Ciummo, V.; Augello, F.R.; Altamura, S.; Lombardi, F.; Latella, G.; Palumbo, P.; Cinque, B. Multi-Strain Probiotic Lysate Attenuates TGF-β1-Induced Intestinal Fibrosis and EMT Modulating Smad, Akt, and WNT/β-Catenin Pathways. Cells 2025, 14, 1432. https://doi.org/10.3390/cells14181432

AMA Style

Ciafarone A, Artone S, Ciummo V, Augello FR, Altamura S, Lombardi F, Latella G, Palumbo P, Cinque B. Multi-Strain Probiotic Lysate Attenuates TGF-β1-Induced Intestinal Fibrosis and EMT Modulating Smad, Akt, and WNT/β-Catenin Pathways. Cells. 2025; 14(18):1432. https://doi.org/10.3390/cells14181432

Chicago/Turabian Style

Ciafarone, Alessia, Serena Artone, Valeria Ciummo, Francesca Rosaria Augello, Serena Altamura, Francesca Lombardi, Giovanni Latella, Paola Palumbo, and Benedetta Cinque. 2025. "Multi-Strain Probiotic Lysate Attenuates TGF-β1-Induced Intestinal Fibrosis and EMT Modulating Smad, Akt, and WNT/β-Catenin Pathways" Cells 14, no. 18: 1432. https://doi.org/10.3390/cells14181432

APA Style

Ciafarone, A., Artone, S., Ciummo, V., Augello, F. R., Altamura, S., Lombardi, F., Latella, G., Palumbo, P., & Cinque, B. (2025). Multi-Strain Probiotic Lysate Attenuates TGF-β1-Induced Intestinal Fibrosis and EMT Modulating Smad, Akt, and WNT/β-Catenin Pathways. Cells, 14(18), 1432. https://doi.org/10.3390/cells14181432

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