Abstract
Osteopontin, which is a highly phosphorylated and glycosylated acidic secreted protein encoded by the secreted phosphoprotein 1 (Spp1) gene, plays a crucial role in immune regulation, inflammatory responses, and cell adhesion. However, its impact on intestinal gene expression and gut microbiota remains underexplored. In this study, we developed an Spp1 conditional knockout mouse model to investigate alterations in the intestinal transcriptome and microbiome, with particular emphasis on changes in gene expression and predicted metabolic pathways. Our findings demonstrated that Spp1 gene conditional knockout significantly modified the expression of genes involved in immune regulation and lipid metabolism. Moreover, metagenomic analysis revealed marked shifts in gut microbial diversity and predicted the metabolic pathways associated with digestion, absorption, and lipid metabolism. These results suggest that Spp1 is instrumental in maintaining gut microbial equilibrium and in regulating host lipid metabolism and immune responses. This study offers new insights into the role of Spp1 in host-microbiota interactions and the potential foundations for developing related therapeutic strategies.