Hyocholic Acid Species as the Key Modulator for Cecal Epithelial Homeostasis in Low-Birth-Weight Piglets.

Background: Low birth weight (LBW) is correlated with gut microbiota dysbiosis and intestinal barrier function disruption, increasing susceptibility to enteric diseases. These alterations underscore the critical need to identify key regulators of gut homeostasis, among which bile acids are increasingly recognized as pivotal for barrier integrity, microbial ecology, and host metabolism. Methods: Eight pairs of LBW (the initial BW was 0.850 ± 0.053 kg) and normal-birth-weight (NBW; 1.488 ± 0.083 kg) piglets were compared to evaluate cecal morphology and bile acid profiles. Subsequently, sixteen LBW piglets and eight NBW piglets were allocated into three groups: NBW (1.563 ± 0.052 kg), LBW control (LBW-CON; 0.950 ± 0.120 kg), and LBW with bile acid supplementation (LBW-bile powder; 0.925 ± 0.116 kg). Piglets in the LBW-bile powder group received 25 mg/kg BW of bile powder (hyodeoxycholic acid-enriched) by daily oral gavage for 14 days. Results: LBW piglets exhibited retarded cecal development and lower abundance of hyocholic acid species (p = 0.006). Importantly, bile powder supplementation significantly improved cecal length (p = 0.009) and mucosal thickness (p = 0.020) compared with LBW-CON piglets. Microbial analysis showed that the microbial dysbiosis index was restored to near-normal levels. Transcriptomic analysis revealed impaired extracellular matrix structure and mucus secretion in LBW piglets. Notably, bile powder supplementation markedly upregulated the protein expression of WNT8B (p < 0.001) and the bile acid receptors (i.e., GPBAR1 and FXR), alongside enhanced tight junctions and the goblet cell marker mucin-2 expression (p < 0.05). Conclusions: These findings suggest that specific bile acid supplementation improves gut barrier function and partially supports cecal development in LBW piglets.