Resveratrol supplementation at 2g daily for 42 days improved growth performance and feed efficiency while reducing diarrhea incidence in early-weaned calves compared to controls. The polyphenol decreased inflammatory IL-1β and oxidative damage marker malondialdehyde while boosting anti-inflammatory IL-4 and antioxidant capacity. Key microbiome changes included increased Parabacteroides, Christensenella, and beneficial short-chain fatty acid producers, alongside enhanced butyric acid and branched-chain fatty acids. This animal study illuminates resveratrol's multi-pathway benefits that likely translate to human health applications. The tryptophan metabolism enhancement is particularly noteworthy, as this pathway influences mood, sleep, and immune function in humans. The Parabacteroides connection suggests resveratrol works through specific bacterial strains rather than broad microbiome effects. While promising for human longevity applications, the calf model has limitations—their developing gut differs significantly from mature human intestines. The 2g dose proportionally scales to roughly 200-400mg for humans, aligning with typical supplement ranges. This mechanistic insight into resveratrol's gut-brain-immune axis effects supports its potential as a targeted longevity intervention, though human trials remain essential.