Dietary Glycerol Monolaurate Enhances Growth and Immune Function in Calves via Hepatic Immunometabolic Reprogramming

Early-life nutrition is critical for the development and health of dairy calves, necessitating alternatives to in-feed antibiotics. This study investigated whether dietary glycerol monolaurate (GML) enhances growth performance, reduces diarrhea incidence, improves systemic antioxidant and immune status, and modulates hepatic immunometabolic function in calves. Twenty-four Holstein bull calves (7 ± 0.5 d of age) were randomly assigned by body weight and age to a control group or a GML-supplemented group, both fed milk replacer with starter feed provided throughout the 45-day trial. Calves in the GML group received GML at a dosage of 100 mg/kg of body weight, mixed into the milk replacer prior to feeding. Calves in the GML group had significantly greater final body weight, average daily gain, and starter intake during the latter period (d 23–45) compared with the control group. GML supplementation also significantly reduced the incidence of diarrhea and fever, alongside lower fecal scores and fewer antibiotic treatments. Plasma analysis revealed enhanced antioxidant capacity, as indicated by increased total antioxidant capacity and glutathione peroxidase, along with an improved immune profile characterized by elevated immunoglobulin G and reduced interleukin-2. Transcriptomic analysis of the liver showed that GML upregulated genes and pathways related to innate antiviral immunity, such as radical S-adenosyl methionine domain containing 2, interferon-stimulated gene 15, and MX dynamin like GTPase 1. Lipidomics further indicated that GML induced a targeted remodeling of hepatic lipids, including increased diacylglycerols and triacylglycerols and decreased specific phospholipids and sphingolipids, suggesting a metabolic shift supportive of immune activation and inflammatory control. In conclusion, dietary GML enhances growth and health in suckling calves, which is mediated through a coordinated immunometabolic reprogramming in the liver. GML represents a promising functional fat additive for sustainable calf rearing.