Cichorium intybus L. polysaccharide improves growth performance and colonic barrier function in weaned piglets via the microbiota-HDCA-TGR5-Akt-NF-κB signaling axis: validation by FMT and in vitro models.

backgroundWeaning stress predisposes piglets to intestinal barrier disruption and gut dysbiosis, which contribute to post-weaning diarrhea and poor feed efficiency. Chicory (Cichorium intybus L.) polysaccharide (CLP) is a fructan-rich prebiotic candidate; however, how CLP reshapes the microbiota-metabolite network to protect the colon remains unclear.

methodsIn Exp. 1, 96 weaned piglets [Duroc × (Landrace × Yorkshire), 28 days old, 8.03 ± 0.2 kg] were fed a basal diet (CON group) or a 0.5% CLP supplemented diet (CLP group). In Exp. 2, fecal microbiota from piglets were transplanted into dextran sulfate sodium (DSS)-induced mice to confirm the causal role of the CLP-remodeled microbiota. Metagenomic and untargeted metabolomic analyses were employed to identify key microbial species and functional metabolites. In Exp. 3, Caco-2 cells were treated with varying concentrations of hyodeoxycholic acid (HDCA) for 24 h to functionally validate the regulatory effects on TGR5 and FXR expression levels.

resultsThe results showed that dietary CLP significantly decreased the feed to gain ratio, diarrhea rate and histology index (P < 0.05), but increased goblet cell numbers (P < 0.05). Metagenomic sequencing revealed that CLP significantly increased microbial α-diversity and remodeled the community structure, specifically enriching beneficial microbes, such as Blautia sp., Eubacterium sp., and Ruminococcus sp. To test microbiota causality, fecal microbiota from CON or CLP piglets was transplanted into antibiotic treated mice followed by DSS challenge. The CLP modified microbiota alleviates DSS induced colitis, upregulated Occludin and ZO-1 expression, and reduced colonic IL-1β and TNF-α levels. Mechanistically, the CLP remodeled microbiota promoted the accumulation of HDCA, which functioned as a signaling ligand to activate the colonic TGR5 receptor. This activation subsequently suppressed the phosphorylation of Akt (P < 0.05), leading to the inhibition of the NF-κB signaling pathway through the reduced phosphorylation of IκBα and the p65 subunit (P < 0.05), thereby effectively abrogating the inflammatory response.

conclusionDietary CLP supplementation mitigates weaning induced intestinal injury and inflammation by remodeling the colonic microbiota, specifically enriching HDCA-producing species. The subsequent activation of the HDCA-TGR5-Akt signaling axis inhibits the NF-κB pathway, thereby improving host immune responses and intestinal barrier function.