N-Acyl-Homoserine Lactones May Affect the Gut Health of Low-Birth-Weight Piglets by Altering Intestinal Epithelial Cell Barrier Function and Amino Acid Metabolism.

ABSTRACT

BACKGROUND: In piglets, low birth weight (LBW) is associated with intestinal dysfunction, which affects their growth performance and causes economic losses. OBJECTIVES: This study was designed to test whether microbial quorum sensing (QS) affects LBW-induced intestinal developmental defects in piglets. METHODS: Seven normal-birth-weight (NBW; 1.36 ± 0.01 kg) and 7 LBW (0.89 ± 0.01 kg) piglets were selected. Feces were collected from piglets on 2, 21, and 50 days of age for detection of the QS signaling molecules, N-acyl-homoserine lactones (AHLs), and microbiota analysis. The associations between 2 long-chain AHLs [N-3-oxo-dodecanoyl-l-homoserine lactone (3OC12-HSL) and N-3-oxo-tetradecanoyl-l-homoserine lactone (3OC14-HSL)] and the microbes were tested using Spearman correlation coefficients. The effect of 3OC12-HSL and 3OC14-HSL on intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell viability was investigated by cholecystokinin octapeptide assay. Transcriptomic analysis was performed by RNA sequencing on cells treated with 3OC12-HSL. RESULTS: The concentrations of 3OC12-HSL and 3OC14-HSL in the feces of LBW piglets were higher than those in NBW piglets at age 50 d by 2.5- and 2.24-fold, respectively (P < 0.05). The microbial α diversity (observed species, abundance-based coverage estimator, and Shannon index) of LBW piglets was 81-91% lower than that of NBW piglets (P < 0.05). The relative abundance of Ruminococcaceae UCG-002/UCG-013 was 43.0% and 30.0% lower, respectively, in feces from LBW compared with NBW piglets (P < 0.05). 3OC12-HSL and Ruminococcaceae UCG-002/UCG-005/UCG-010 abundance were negatively correlated (ρ  ≤  -0.58). Treatment with 400 µM 3OC12-HSL markedly reduced IPEC-J2 cell viability by 47.5%. Transcriptomic data showed that 3OC12-HSL mainly changed the "import across plasma membrane" and "arginine and proline metabolism" of IPEC-J2 cells. CONCLUSIONS: 3OC12-HSL is a QS signaling molecule with an ability to impair gut health of LBW piglets. This finding adds to our understanding of the mechanisms responsible for gut injury in LBW piglets.