Gut microbiota dysbiosis and exosomal miRNA signatures in piglets with intrauterine growth restriction

Abstract Intrauterine growth restriction (IUGR) in newborn animals is linked to impaired intestinal health, yet the characteristics of their gut microbiota and circulating exosomal miRNAs remain incompletely understood. This study compared the cecal microbiota composition and serum exosomal miRNA profiles to characterize differences between IUGR and normal birth weight (NBW) piglets. Compared to NBW piglets, IUGR piglets displayed significant reductions in body and organ weights (heart, liver, kidney) as well as shorter jejunal and ileal lengths ( p < 0.05). Microbial diversity, reflected by the Chao1 and Shannon index, was significantly reduced in IUGR piglets ( p < 0.001). Taxonomic analysis revealed decreased abundances of Bacteroidetes, Fusobacteria , and Fusobacterium ( p < 0.05), alongside increased abundances of potential pathogenic taxa, including Proteobacteria, Escherichia-Shigella , and Sutterella ( p < 0.05). Moreover, three serum exosomal miRNAs (ssc-miR-16, ssc-miR-19b, and ssc-let-7c) emerged from the analysis as potential key regulators of IUGR. Functional enrichment analysis revealed that ssc-miR-16 and ssc-miR-19b were significantly increased in IUGR piglets, mainly targeting genes involved in cellular signaling, metabolism, and immune regulation, including the mTOR and infection-related pathways. In contrast, ssc-let-7c was significantly downregulated and linked to metabolic processes such as protein digestion and absorption. Collectively, these findings demonstrate that IUGR disrupts intestinal barrier development and microbial homeostasis, while identifying three serum exosomal miRNAs as potential biomarkers and mechanistic contributors to the pathological processes underlying IUGR.