Short-term supplementation of thymol and carvacrol regulates feed intake via the hypothalamic PI3K/AKT/SF-1 pathway and influences intestinal traits in chicks.

INTRODUCTION: This study investigated the effects of dietary supplementation with thymol, carvacrol, and NE150 (a commercial blend containing 25% thymol and 25% carvacrol) at 120 mg/kg on growth performance and feed intake, hypothalamic appetite-regulating gene expression and PI3K/AKT/SF-1 signaling, as well as intestinal morphology and cecal microbiota in broiler chicks. METHODS: Based on preliminary dose-finding experiments (60, 120, and 240 mg/kg), the 120 mg/kg dose was selected for each additive as it showed the most favorable effects on growth performance (data not shown). A total of 180 one-day-old Arbor Acres male chicks were fed a basal diet from day 1 to 10, followed by a 3-day treatment period (days 10-13) with the respective diets. RESULTS: Compared with the control group, total feed intake at 72 h was reduced by thymol, carvacrol, and NE150 (P < 0.05). Dietary supplementation with these compounds at 120 mg/kg upregulated the hypothalamic mRNA expression of pro‑opiomelanocortin and steroidogenic factor-1 (SF-1), while downregulating neuropeptide Y (P < 0.05). These treatments also increased the mRNA levels of cholecystokinin and glucagon‑like peptide‑1 receptor in both the hypothalamus and jejunum, and enhanced the protein expression of SF-1, p-PI3K, p-AKT473, p-AKT308, p-S6, and p-mTOR in the hypothalamus (P < 0.05). Furthermore, supplementation with carvacrol or NE150 improved the jejunal villus height to crypt depth ratio, and all three additives modulated the cecal microbiota by increasing microbial richness and diversity, as indicated by higher OTU numbers and Shannon index (P < 0.05). DISCUSSION: These findings indicate that thymol and carvacrol suppress feed intake in broiler chicks, at least in part, through activation of the hypothalamic PI3K/AKT/SF-1 pathway, while also improving intestinal morphology and cecal microbiota composition. These results suggest that thymol and carvacrol may serve as effective antibiotic alternatives in poultry nutrition.