Longitudinal metagenome–blood transcriptome profiling reveals accelerated gut microbial maturation in infant rhesus macaques

The parallel dynamics of gut microbiota and host gene expression during early life remain poorly understood, especially in non-human primates. Here, we conducted a longitudinal multi-omics study of 21 captive infant rhesus macaques (Macaca mulatta), collecting 143 blood transcriptomes and 144 fecal metagenomes across 7 time points over 468 days (6–22 months of age), and compared them with 340 published human gut metagenomes spanning newborns to adults. While the core metagenomic functional potential remained relatively stable, both microbial composition and host gene expression showed pronounced stage-specific dynamics. Metagenomic shifts were strongly associated with concurrent dietary and housing transitions; five community types recurrently shifted before converging toward an adult-like configuration, and core metabolic pathway abundances fluctuated in concert with community shifts. In contrast, blood transcriptomic dynamics predominantly reflected developmental and immunological programs. Compared by chronological age, macaque microbiota appeared to mature earlier than human microbiota, although this difference may partly reflect interspecies differences in weaning timing; alpha diversity was also significantly higher in macaques. Despite these differences, core genera were largely shared, and we delineated host- and age-enriched taxa with contrasting trajectories. These findings support the infant macaque as a useful translational model that partially recapitulates human gut microbiome development while revealing important differences in maturation timing, providing a paired multi-omics reference for future host–microbiome interaction studies.