Abstract:[Objective] This study aimed to investigate the effects of goat milk formula powder on lipopolysaccharide (LPS)-induced intestinal inflammation and barrier impairment in mice.[Method] Histopathological observation, real-time quantitative PCR, and enzyme-linked immunosorbent assay were used to assess changes in intestinal inflammation levels and barrier function-related indicators in mice following intervention with goat milk formula powder. Additionally, the composition of the gut microbiota was analyzed to elucidate its potential mechanisms of action.[Result] Goat milk formula powder alleviated intestinal histopathology and increased the number of goblet cells. Compared with the model group, the goat milk formula powder intervention reduced the mass fractions of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 by 21.88%, 28.30%, and 36.67%, respectively, while it increased the mass fraction of the anti-inflammatory cytokine IL-10 by 53.80%. Regarding intestinal permeability markers, it reduced the mass concentrations of D-lactate and enterotoxin by 16.14% and 32.52%, respectively, and decreased the activity of diamine oxidase (DAO) by 8.74%. Meanwhile, it enhanced the mRNA expression levels of tight junction [proteins ZO-1 and Claudin-1 by 2.50- and 2.89-fold. Furthermore, the intervention increased the relative abundance of beneficial gut bacteria, including Akkermansia, Alistipes, Alloprevotella, and Muribaculum, and these microbial changes were correlated with the aforementioned inflammation and intestinal barrier indicators.Conclusion] Goat milk formula powder alleviated LPS-induced intestinal inflammation and enhanced barrier function in mice, with its mechanism of action potentially related to modulation of the gut microbiota structure.