Biology subjects

Lencina, C.

Publications and source records attributed to Lencina, C..

2 recordsLinked to original sources

bioRxiv2025

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 amino acids produces a wide variety of metabolites whose effects on the intestinal epithelium remain to be fully identified. In this study, we investigated the effects of amino acid derived metabolites (isovalerate, isobutyrate, 2-methylbutyrate, 5-aminovalerate, cadaverine, putrescine, and tryptamine) in cell monolayers derived from porcine ileum organoids. Our results show that the leucine-derived branched-chain fatty acid (BCFA) isovalerate improved the epithelial barrier function, as assessed by transepithelial electrical resistance measurement and permeability assay. Isovalerate upregulated the expression of genes involved in innate immunity, markers of absorptive cells and enteroendocrine cells while reducing the expression of the stem cells and mucus related genes. Most of the effects of isovalerate on epithelial cells were also observed with the bacterial metabolite butyrate, an inhibitor of the epigenetic enzymes histone deacetylases (HDAC). Furthermore, the structurally unrelated HDAC inhibitor trichostatin A improved epithelial barrier function and upregulated SLPI gene expression, as observed with isovalerate and butyrate. Isovalerate also upregulated the gene expression of antioxidant enzymes and this effect was not observed with butyrate. Interestingly, the other two BCFAs isobutyrate and 2-methylbutyrate did not replicate the effects of isovalerate, suggesting that the carbon chain structure of isovalerate mediates its effect. In contrast, we found that all three BCFAs were able to cross the epithelial cell monolayer derived from porcine ileum organoids from the apical to the basal side. Overall, our in vitro results suggest that targeting the bacterial production of isovalerate may be useful to promote gut health. In this perspective, we performed an in silico analysis that identified species belonging to dominant gut microbiota genera such as Prevotella, Blautia, Christensenella, Clostridium, and Ruminococcus, as potential producers of BCFAs through the PorA enzymatic pathway.

cell biology↗

bioRxiv2024

A single-cell atlas of transcriptome changes in the intestinal epithelium at the suckling-to-weaning transition

The suckling-to-weaning dietary transition is a key step in mammalian intestinal development. However, the relative contributions of genetically wired and nutritional factors in this maturation process remain to be elucidated. Moreover, the cellular diversity of the intestinal epithelium has been overlooked in this context. The aim of our study was to identify the transcriptome changes induced in each cell type of the intestinal epithelium at the onset of solid food ingestion. We compared the single-cell transcriptome of epithelial cells isolated from the caecum of age-matched littermate suckling rabbits ingesting or not solid food. Our dataset provides the first single-cell atlas of the rabbit intestinal epithelium and highlights the interest of the rabbit as a model for studying BEST4+ epithelial cells, which are absent in mice. Solid food ingestion induced extensive transcriptome changes in each epithelial cell type, with the most pronounced changes noted in absorptive and BEST4+ cells. Some of the effects of solid food introduction were common to most epithelial cell types, such as the upregulation of ALDH1A1, which encodes for a vitamin A processing enzyme. Solid food ingestion remodeled epithelial defenses systems, as observed by the increased expression of interferon-stimulated genes in mature absorptive and BEST4+ cells. Solid food also upregulated the gene expression of the immunoglobulin transporter PIGR, specifically in cells located at the base of epithelial crypts and in goblet cells. In addition, solid food triggered epithelial differentiation, which was associated with modification of the expression of genes involved in handling of amino acids, lipids and bile acids, as well as changes in hormone expression by enteroendocrine cells. These cell type-specific transcriptome modifications induced by solid food ingestion coincided with changes in microbiota composition and metabolic activity, which may contribute to epithelial maturation. Overall, our work provides a single-cell atlas of the transcriptome changes induced in the intestinal epithelium at the suckling-to-weaning transition.

physiology↗