<i>Lactobacillus acidophilus</i> Postbiotics Differentially Modulate Nutrient Sensing, Intestinal Barrier Integrity, and Inflammatory Signaling in Broiler

ABSTRACT The global restriction of antibiotic growth promoters (AGPs) has accelerated the search for sustainable nutritional alternatives that support growth performance and intestinal health of poultry. Postbiotics and their bioactive metabolites derived from probiotic microorganisms have emerged as promising candidates due to their functional stability and immunometabolic regulatory potential. This study evaluated the effects of Lactobacillus acidophilus ‐derived postbiotics on growth performance, nutrient sensing, intestinal barrier integrity, immune response, antioxidant status, and gut microbiota in broiler chickens. For this purpose, a total of 400 day‐old broilers were randomly assigned to four dietary treatments with graded postbiotic supplementation (0.0%, 0.5%, 1.0%, and 2.0%) for 42 days. Growth performance, immune and antioxidant indices, intestinal and hepatic histomorphology, gene expression, and cecal microbial composition were assessed. Broilers receiving 1.0% and 2.0% postbiotics exhibited significantly higher average daily gain and feed intake compared with controls ( p &lt; 0.05). Postbiotic supplementation enhanced systemic immunity, reflected by increased serum IgA, IgG, and IgM levels and elevated spleen and bursa indices. Improved intestinal morphology was evidenced by increased duodenal villus height and villus height‐to‐crypt depth ratio, while hepatic tissues showed reduced inflammation and fibrosis. Molecular analyzes revealed upregulation of nutrient transporters (SGLT1, PepT1), tight junction protein ZO‐1, and antioxidant enzyme GPX1, alongside downregulation of pro‐inflammatory cytokines (IL‐1β and IL‐6). Additionally, postbiotics increased the abundance of beneficial cecal taxa, including coliforms, Lactobacillus, and total plate count. Collectively, L. acidophilus ‐derived postbiotics improve broiler performance by coordinating nutrient transporter regulation, antioxidant signaling, and inflammatory control, supporting their application as a sustainable AGPs alternative.