Dihydroquercetin attenuated Prevotella copri-caused intestinal injury by modulating gut microbiota and bile acids in weaned piglets

Gut microbiota disruption during the weaning process is a significant factor of intestinal injury. Our previous studies have suggested that <i>Prevotella</i> may play a critical role in causing intestinal inflammation. This study aimed to clarify the impact of <i>Prevotella copri</i> on intestinal injury and the protecting effect by dihydroquercetin (DHQ) in weaned piglets. A total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly allocated into 3 groups with 6 replicates and 6 piglets per replicate. The piglets were the following diets for 28 d: 1) a basal diet, 2) basal diet containing 1.0 × 10⁸ CFU/kg <i>P. copri</i>, 3) basal diet supplemented with 1.0 × 10⁸ CFU/kg <i>P. copri</i> and 100 mg/kg DHQ. Results showed that <i>P.</i> copri decreased significantly the average daily gain (ADG) (<i>P</i> < 0.001), which was recovered by supplementation of DHQ with decreased serum levels of malondialdehyde (MDA), interleukin (IL)-2 and IL-8 but increased total superoxide dismutase (T-SOD) activity and IL-10 in weaned piglets (<i>P</i> < 0.001). Moreover, DHQ increased the expression of tight junction proteins (claudin-2, occludin and tight junction protein zonula occludens protein-1 (ZO-1) and the mRNA expression of glutathione peroxidase 4 (<i>GPX-4</i>) in ileum (<i>P</i> < 0.001). Intestinal flora analysis showed that <i>P. copri</i> increased the relative abundance of <i>Prevotella</i> (<i>P =</i> 0.026) and <i>Eubacterium coprostanoligenes group</i> (<i>P</i> < 0.001), but decreased the relative abundance of Lachnospiraceae <i>NK4A136 group</i> (<i>P</i> < 0.001), while supplementation of DHQ reduced the relative abundance of <i>Prevotella</i> (<i>P =</i> 0.026). Metabolomics results indicated that <i>P. copri</i> enhanced the content of 12-OH bile acid, but decreased the contents of glycodeoxycholic acid (GDCA) and glycochenodeoxycholic acid (GCDCA) (<i>P</i> < 0.001), while DHQ reduced the 12-OH bile acid content (<i>P</i> < 0.001) and increased the GDCA content (<i>P =</i> 0.020). In summary, <i>P. copri</i> caused intestinal injury and reduced growth performance in weaned piglets, and DHQ showed a protective effect by modulating gut microbiota and bile acids metabolism.