1H NMR-Based Urinary Metabolic Profiling Reveals Changes in Nicotinamide Pathway Intermediates Due to Postnatal Stress Model in Rat

The maternal separation protocol in rodents is a widely recognized model of early life stress allowing acute and chronic physiological consequences to be studied. An 1H NMR-based metabolomic approach was applied to urines to evaluate the systemic metabolic consequences of maternal separation stress in female rats after the beginning of weaning and 4 weeks later when the rats were reaching adulthood. Furthermore, because maternal separation is considered as a model mimicking the inflammatory bowel syndrome, the lactulose/mannitol test was used to evaluate the influence of postnatal maternal separation on gut permeability and mucosal barrier function by 1H NMR spectroscopy analysis of urine. The results showed no statistical differences in gut permeability due to maternal separation. The application of ANOVA simultaneous component analysis allowed the contributions of physiological adaptations to the animals development to be separated from the metabolic consequences due to postnatal stress. Systemic metabolic differences in the maternally separated pups were mainly due to the tryptophan/NAD pathway intermediate levels and to the methyladenosine level. Urinary NMR-based metabolic profiling allowed us to disentangle the metabolic adaptive response of the rats to postnatal stress during the animals growth, highlighting the metabolic changes induced by weaning, gut closure, and maturity.