A mix of functional amino acids and grape polyphenols promotes the growth of piglets, modulates the gut microbiota in vivo and regulates epithelial homeostasis in intestinal organoids.

Weaning is a challenging period for gut health in piglets. Previous studies showed that dietary supplementations with either amino acids or polyphenols promote piglet growth and intestinal functions, when administered separately. Thus, we hypothesized that a combination of amino acids and polyphenols could facilitate the weaning transition. Piglets received during the first two weeks after weaning a diet supplemented or not with a mix of a low dose (0.1%) of functional amino acids (L-arginine, L-leucine, L-valine, L-isoleucine, L-cystine) and 100 ppm of a polyphenol-rich extract from grape seeds and skins. The mix of amino acids and polyphenols improved growth and feed efficiency. These beneficial effects were associated with a lower microbiota diversity and a bloom of Lactobacillaceae in the jejunum content while the abundance of Proteobacteria was reduced in the caecum content. The mix of amino acids and polyphenols also increased the production by the caecum microbiota of short-chain fatty acids (butyrate, propionate) and of metabolites derived from amino acids (branched-chain fatty acids, valerate, putrescine) and from polyphenols (3-phenylpropionate). Experiments in piglet jejunum organoids revealed that the mix of amino acids and polyphenols upregulated the gene expression of epithelial differentiation markers while it reduced the gene expression of proliferation and innate immunity markers. In conclusion, the supplementation of a mix of amino acids and polyphenols is a promising nutritional strategy to manage gut health in piglets through the modulation of the gut microbiota and of the epithelial barrier.

Developmental Stage, Solid Food Introduction, and Suckling Cessation Differentially Influence the Comaturation of the Gut Microbiota and Intestinal Epithelium in Rabbits.

BACKGROUND: In mammals, the establishment around weaning of a symbiotic relationship between the gut microbiota and its host determines long-term health. OBJECTIVES: The aim of this study was to identify the factors driving the comaturation of the gut microbiota and intestinal epithelium at the suckling-to-weaning transition. We hypothesized that the developmental stage, solid food ingestion, and suckling cessation contribute to this process. METHODS: From birth to day 18, Hyplus rabbits were exclusively suckling. From day 18 to day 25, rabbits were 1) exclusively suckling; 2) suckling and ingesting solid food; or 3) exclusively ingesting solid food. The microbiota (16S amplicon sequencing), metabolome (nuclear magnetic resonance), and epithelial gene expression (high-throughput qPCR) were analyzed in the cecum at days 18 and 25. RESULTS: The microbiota structure and metabolic activity were modified with age when rabbits remained exclusively suckling. The epithelial gene expression of nutrient transporters, proliferation markers, and innate immune factors were also regulated with age (e.g., 1.5-fold decrease of TLR5). Solid food ingestion by suckling rabbits had a major effect on the gut microbiota by increasing its α diversity, remodeling its structure (e.g., 6.3-fold increase of Ruminococcaceae), and metabolic activity (e.g., 4.6-fold increase of butyrate). Solid food introduction also regulated the gene expression of nutrient transporters, differentiation markers, and innate immune factors in the epithelium (e.g., 3-fold increase of nitric oxide synthase). Suckling cessation had no effect on the microbiota, while it regulated the expression of genes involved in epithelial differentiation and immunoglobulin transport (e.g., 2.5-increase of the polymeric immunoglobulin receptor). CONCLUSIONS: In rabbits, the maturation of the microbiota at the suckling-to-weaning transition is driven by the introduction of solid food and, to a lesser extent, by the developmental stage. In contrast, the maturation of the intestinal epithelium at the suckling-to-weaning transition is under the influence of the developmental stage, solid food introduction, and suckling cessation.