Polygonatum sibiricum, a tonic and functional food, ameliorates poor lifestyle-induced sub-health by regulating gut microbiota and kynurenine metabolism

Sub-health is a state between disease and health, characterized by unexplained fatigue and negative emotions. Imbalance of gut microbiota and aberrant Trp-Kyn metabolism are deeply involved in the pathogenesis of sub-health. Polygonatum sibiricum is a functional food demonstrated efficacy in combating fatigue, alleviating depression, and promoting intestinal health, suggesting its potential for sub-health. This study aimed to identify the effects of P. sibiricum aqueous extract (PSAE) on sub-health and explore the underlying mechanism. A sub-health rat model was established by simulating unhealthy lifestyles, including poor diet, irregular sleep, excessive work, and overstress. PSAE was administered orally at doses of 0.25 g/kg, 0.5 g/kg, and 1.0 g/kg. Following a 4-week intervention, sub-health symptoms in rats intervened with PSAE, including fatigue, negative emotions, and disorders in neuroendocrine-immune, were alleviated. It increases gut microbiota diversity and reshapes its composition to resemble healthy rats. PSAE also elevates serum levels of PA, NAD + , and ATP, and the ratios of XA,3-HK,3-HA, PA to Kyn in the Kyn pathway, upregulates metabolic enzymes in the liver (TDO2, KMO, KAT1). Analysis showed that metabolites and enzyme expression in the Kyn pathway were correlated with general physical, physical endurance, and emotional changes. Furthermore, Muribaculaceae Ruminococcus, Eggerthellaceae , etc. , showed positive correlations with the Kyn pathway. PSAE supplementation may prevent sub-health induced by poor lifestyle by modulating gut microbiota composition and Kyn metabolism. • This study offers a healthy functional food for sub-health from a poor lifestyle. • Polygonatum sibiricum (PS) fights sub-health by relieving fatigue, regulating mood, and correcting neuroendocrine imbalances. • PS targets sub-health via regulating Kyn metabolism and dysbacteriosis.