Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites.

Background/Objective: Aging is a significant risk factor for chronic diseases and disability, yet effective anti-aging interventions remain elusive. We explored the potential of 3-hydroxybutyrate (3HB), an endogenous metabolite with established safety, to modulate longevity in mice. Methods: In this study, we employed 2BS and WI-38 cell models, a yeast model, and naturally aging mouse models to investigate the effects of 3HB on aging in various systems. Additionally, we utilized RNA sequencing and metabolomics technologies to explore the potential mechanisms underlying the action of 3HB. Results: Our findings demonstrate that 3HB supplementation effectively delays cellular senescence, extending yeast lifespan by 51.3% and the median lifespan of naturally senescent mice by 21.0%. Notably, 3HB prolonged healthy lifespan in mice while mitigating age-related tissue morphology changes and organ senescence. Mechanistically, we identified that 3HB’s anti-aging properties are mediated through its ability to delay cellular senescence and metabolic reprogramming, while promoting the production of beneficial metabolites like trigoneline and isoguvacine. Conclusions: These findings highlight the promising therapeutic potential of 3HB as an anti-aging intervention and provide novel insights into its underlying mechanisms.