The gut microbiota metabolite isovalerate enhances the epithelial barrier function in cell monolayers derived from porcine ileum organoids
The gut microbiota produces numerous metabolites that influence the epithelial barrier function. Bacterial catabolism of aminoacids produces a wide variety of metabolites whose effects on the intestinal epithelium remain to be identified. In this study, weinvestigated the effects of amino acid-derived...
| Autores: | , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2026 |
| País: | España |
| Recursos: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:dnet:idus________::16f007d2b2ce35eedf86ee77ed19d370 |
| Acesso em linha: | https://hdl.handle.net/11441/186297 https://doi.org/10.1152/ajpgi.00193.2025 |
| Access Level: | acceso abierto |
| Palavra-chave: | Branched-chain fatty acids Enteroids Epithelium Isovaleric acid Protein fermentation |
| Resumo: | The gut microbiota produces numerous metabolites that influence the epithelial barrier function. Bacterial catabolism of aminoacids produces a wide variety of metabolites whose effects on the intestinal epithelium remain to be identified. In this study, weinvestigated the effects of amino acid-derived metabolites (isovalerate, isobutyrate, 2-methylbutyrate, 5-aminovalerate, cadaver-ine, putrescine, and tryptamine) in cell monolayers derived from porcine ileum organoids. Our results show that the branched-chain fatty acid (BCFA) isovalerate improved the epithelial barrier function, as assessed by transepithelial electrical resistancemeasurement and paracellular permeability assay. Isovalerate upregulated the expression of genes involved in innate immunity,markers of absorptive and enteroendocrine cells, while reducing the expression of stem cells and mucus-related genes. Most ofthe effects of isovalerate on epithelial cells were also observed with butyrate, an inhibitor of the epigenetic enzymes histonedeacetylases (HDAC). We found that isovalerate also inhibited HDAC, although to a lesser extent than butyrate. Furthermore, thestructurally unrelated HDAC inhibitor trichostatin A improved epithelial barrier function and upregulated SLPI and IL10RA geneexpression, as observed with isovalerate and butyrate. Interestingly, the other two BCFAs, isobutyrate and 2-methylbutyrate, didnot replicate the effects of isovalerate. Overall, our in vitro results suggest that targeting the bacterial production of isovaleratemay be useful to promote gut health. In this perspective, we performed an in silico analysis that identified species belonging todominant gut microbiota genera, such as Prevotella, Blautia, Christensenella, Clostridium, and Ruminococcus, as potential pro-ducers of BCFAs through the POR enzymatic pathway. |
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