Immune stress impairs broiler performance by affecting hypothalamic methylation modification and intestinal 5-HT synthesis

In this experiment, a chronic immune stress model was established in broiler chickens by injecting lipopolysaccharide (LPS). The objective was to investigate the impact of immune stress on performance and intestinal mucosal barrier function in broiler chickens and identify key molecular and neuroendocrine pathways contributing to these effects. We randomly divided 160 one-day-old male white-feathered broilers into two groups: the control group (CON) and the LPS immune stress group (LPS), with 8 replicates of 10 chickens each. The LPS group received 0.5 mg/kg body weight LPS injections at 14 days of age for 10 consecutive days, while the control group received saline injections. The results indicated that LPS injection significantly decreased broiler performance (P < 0.05) and increased immune organ indices and serum corticosterone levels (P < 0.05). The mRNA levels of IL-1β in the spleen, as well as TNF-α, IL-1β, and FABP1 in the ileum, and hypothalamic MCH and PREPRO, showed significant upregulation (P < 0.05). Conversely, the mRNA levels of CHGA, JAM2, PCNA, BCL2, and mTOR were significantly decreased in the ileum, along with a notable decrease in hypothalamic NPY (P < 0.05). There was also a tendency toward lower expression of mTOR protein in the ileum (P = 0.054). Moreover, serum 5-hydroxytryptamine (5-HT) levels and gene expression of 5-HT receptors in the ileum were significantly reduced (P < 0.05). Additionally, there was a significant increase in m⁶A methylation in both the hypothalamus and ileum (P < 0.05), affecting genes involved in neurotransmitter metabolism and signaling in the hypothalamus. Collectively, these findings suggest that LPS-induced immune stress inhibits the mTOR/P70S6K pathway in the ileum, suppresses intestinal 5-HT synthesis, and impairs intestinal mucosal barrier function. Immune stress also affects m⁶A RNA methylation and appetite-related gene expression in the hypothalamus, leading to reduced broiler performance.