# Effects of Proanthocyanidins on Growth Performance, Intestinal Inflammation and Barrier Function, and Bile Acid Metabolism-Related Genes in Weaned Piglets Challenged with Lipopolysaccharide

## TL;DR

This study shows that proanthocyanidins improve growth and intestinal health in piglets challenged with LPS by activating TGR5 and increasing GLP-2.

## Contribution

The study reveals a novel mechanism by which PAC mitigates LPS-induced intestinal inflammation via TGR5 and GLP-2 activation.

## Key findings

- PAC supplementation increased average daily gain and improved intestinal morphology in LPS-challenged piglets.
- PAC reduced intestinal inflammation and enhanced barrier function by upregulating Occludin and ZO-1 and downregulating TNF-α and IL-6.
- PAC increased GLP-2 levels and activated TGR5, but had no effect on bile acid metabolism-related genes.

## Abstract

The implications of growth performance, intestinal inflammation, barrier function, and bile acid metabolism-related genes in immune-stressed weaning piglets by proanthocyanidins (PACs) are observed. The results indicate that dietary supplementation with PAC was capable of improving the growth performance and intestinal health of LPS-challenged piglets. The beneficial effects of PAC towards the intestinal barrier function and inflammatory responses of piglets appeared to be attributed to the activation of TGR5 and subsequent secretion of GLP-2. These results are of significant scientific importance as they provide novel insights into the mechanisms by which PAC can mitigate the adverse effects of LPS-induced inflammation and improve intestinal health in weaned piglets.

This study aims to investigate the effects of dietary proanthocyanidins (PACs) on growth performance, intestinal inflammation and barrier function, and bile acid metabolism-related genes in weaned piglets challenged with lipopolysaccharide (LPS). A total of 18 21-day-old castrated piglets (7.16 ± 1.66 kg) were randomly assigned to three groups: (1) CON (a basal diet), (2) LPS (a basal diet + LPS), (3) LPS + PAC (a basal diet + LPS + 250 mg/kg PAC), with each group consisting of six replicates of 1 piglet per treatment. The study lasted for 21 days. On the 14th and 21st days of the experiment, piglets in the LPS and LPS + PAC groups received an intraperitoneal injection of 100 µg/kg body weight of LPS, while the piglets in the CON group received an injection of 0.9% normal saline solution. The LPS + PAC group exhibited a significantly higher average daily gain (ADG) than the LPS group (p < 0.05). LPS stimulation resulted in a decreased (p < 0.05) villus height of the jejunum and ileum and an increased number of goblet cells. These effects were alleviated (p < 0.05) in the LPS + PAC group. The LPS + PAC group decreased the level of TNF-α and D-lactate in serum and the gene expression of IL-6 and IL-1β in the ileal tissue, compared with the LPS group, while increasing the gene expression of Occludin and ZO-1 in the ileal tissue (p < 0.05). LPS stimulation down-regulated the expression of genes regulating bile acid synthesis and transport, including hepatic CYP7A1 and ileum ASBT, whereas dietary PAC had no significant effect on the expression of these genes (p > 0.05). Nevertheless, supplementation with PAC significantly increased the expression levels of GLP-2R, GCG, and TGR5 in the ileum of piglets (p < 0.05). Additionally, piglets in the LPS + PAC group exhibited a significant increase in the level of glucagon-like peptide 2 (GLP-2) compared with the LPS group (p < 0.05). PAC generally improves the ADG, intestinal morphology, and intestinal barrier function of piglets by activating TGR5 to stimulate the intestinal secretion of GLP-2.