Modulating Blood-Brain Barrier Metabolites of Broiler Chickens Through Dietary Flaxseed Oil

Dietary polyunsaturated fatty acids (PUFAs) are vital for brain health and cognitive function. The dorsal raphe nucleus (DRN) regulates mood via serotonin, while the hypothalamus (HYP) controls energy homeostasis. Flaxseed oil (FLAX) is rich in omega-3 PUFAs like α-linolenic acid (ALA), and has been reported to influence serotonergic signaling in mammals, but data in poultry are scarce. This study investigated the effects of FLAX on metabolites crossing the blood-brain barrier (BBB) to serotonergic brain regions and on growth performance in broiler chickens. Day-old chicks (n = 160) were assigned to two diets (5 replicates/treatment): control (CON; poultry fat-based diet) or FLAX (3% inclusion level). Growth performance was recorded, and DRN, HYP, and plasma were analyzed using HPLC-MS metabolomics. Serotonin and its metabolite 5-HIAA were quantified using LC-MS/MS. FLAX-fed birds had higher body weight gain (p < 0.0055) and better feed conversion ratio (p < 0.0049) than CON. Metabolomics identified 2271 features, of which 650 were annotated as metabolites. Of 35 differentially abundant plasma metabolites, eight were also differentially abundant in brain tissues. In the DRN, tryptophan (serotonin precursor) and corydaline (neuroprotective) were upregulated. Serotonin levels were significantly higher in both the DRN and HYP of FLAX-fed birds compared to CON. This suggest that dietary flaxseed oil may modulate stress responses, behavior, and welfare in broilers. In the HYP, dethiobiotin (energy), galanthamine (neuroprotective), and gambogic acid (antioxidative) were upregulated, while xanthoxyletin (anti-inflammatory) was downregulated. In conclusion, flaxseed oil improved growth and elevated serotonin in the DRN and HYP via enhanced tryptophan availability, suggesting potential benefits for stress resilience and welfare.