Early gut microbial and metabolic dysregulation with subclinical cardiac alterations in a nonhuman primate model of Rett syndrome.

Longitudinal multi-omics profiling of a nonhuman primate Rett syndrome (RTT) model reveals early systemic alterations. RTT monkeys exhibited postnatal growth retardation, intestinal structural abnormalities, and low-grade systemic inflammation. Gut microbiome analysis showed delayed microbial maturation and age-discordant dysbiosis, including altered Firmicutes/Bacteroidetes ratios and persistent community restructuring. Fecal metabolomics revealed reduced short-chain fatty acids (SCFAs), disrupted microbe-metabolite networks, and broad alterations in lipid, amino acid, and energy metabolism. Electrocardiogram (ECG) identified prolonged corrected QT interval (QTc) and subclinical cardiac electrophysiological changes. Integrated multi-omics analyses indicate that RTT involves early, coordinated dysregulation across gut microbial, metabolic, immune, and peripheral physiological systems, supporting its characterization as a systemic disorder from the early postnatal stage.