Resveratrol ameliorates early-weaning stressed calves via alterations in gut microbiome and metabolome

Early weaning disrupts gut microbiota homeostasis and increases oxidative stress and inflammation in calves, thus negatively affecting their growth performance and health. Resveratrol is a polyphenol with antioxidant and anti-inflammatory properties that modulates gut microbiota and metabolites. In the present study, we investigated the effects of resveratrol on growth performance, immune function, antioxidant capacity, gut microbiota, and metabolic pathways in early-weaning calves. Thirty-six newborn Simmental × Holstein F₁ generation female calves were randomly assigned to one of 3 treatment groups: conventional weaning at 63 d of age (CON), early weaning at 49 d of age (EW), or early weaning at 49 d of age with 2 g/d resveratrol supplementation from d 7 to d 49 (EWR). The results revealed that the final BW, ADG, and feed efficiency were greater in the EWR group than in the CON group, and diarrhea incidence was significantly reduced. The EWR treatment decreased the concentrations of the proinflammatory cytokine IL-1β and the oxidative damage product malondialdehyde. Meanwhile, resveratrol supplementation increased the anti-inflammatory cytokine IL-4, catalase, and the total antioxidant capacity in early-weaning calves, which were not significantly different from CON group. In addition, EWR increased the abundance of Parabacteroides, Eubacterium_coprostanoligenes_group, Christensenella, and Ruminococcaceae, as well as increased concentration of butyric acid, valeric acid, isobutyric acid, isovaleric acid, and total branched short-chain fatty acids. Metabolomic analysis revealed that resveratrol significantly enhanced the tryptophan metabolic pathway. Correlation analysis suggested that Parabacteroides was closely related to the modulatory effects of resveratrol in early-weaning calves through its involvement in tryptophan metabolism. In conclusion, dietary resveratrol supplementation improves growth performance and reduces diarrhea in early-weaning calves by alleviating inflammation and oxidative stress, modulating gut microbiota, and enhancing microbial tryptophan metabolism.