Eucommiae cortex polysaccharides mitigate Western diet-induced cognitive and social dysfunction via modulation of gut microbiota and tryptophan metabolism

The Western diet (WD) is associated with low-grade chronic inflammation and neurodevelopmental disorders. However, the effects of WD during adolescence on future health have been unclear.Eucommiae cortex polysaccharides (EPs) exhibit potential immunomodulatory and neuroprotective effects.Four-week-old mice fed with WD for four weeks, simulating persistent WD in adolescents, exhibited cognitive and social-behavioral deficits.Oral EPs restored physiological hypoxia of colonocytes and inhibited gut dysbiosis, thereby reducing serum endotoxin and subsequent neuroinflammation.Moreover, EPs supplementation suppressed the peripheral kynurenine (Kyn) pathway. It reduced the concentration of quinolinic acid (QA) and glutamic acid in the hippocampus, which reversed hyperactivation of mossy cells (MCs) and impairment of parvalbumin (PV) interneurons-related local circuits, rescuing adult neurogenesis defects and behavioral anomalies in WD-fed mice.