D-glucaro-1,4-lactone Alleviates Acetaminophen-Induced Hepatotoxicity in Mice via Modulating Gut Microbiota and Metabolites Associated with Lactobacillus-Glutamine and Nicotinic Acid Pathways

Zhiying Song¹Yiran Pan²Zeyu Wang²Yujing Chen²Yufeng Deng¹Lele Wang²Qi Hu¹Wenxiang Huang²Shuilin Sun^1*Baogang Xie^3*

• ¹Department of Infectious Diseases, the Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China
• ²Medical College of Jiaxing University, Key Laboratory of Medical Electronics and Digital Health of Zhejiang Province, Jiaxing University, Jiaxing, China
• ³Modern Industrial College of Traditional Chinese Medicine and Health, Lishui University, Lishui, China

, an active ingredient from various vegetables and fruits, has attracted extensive attention due to its pharmacological activities. However, the potential beneficial effects of 1,4-GL on mice with acetaminophen (APAP)-induced acute liver injury (ALI) have not been investigated.Here, administration of 1,4-GL (200.0 mg/kg) resulted in significant improvements in serum biochemical indices and alleviation of pathological liver tissue damage in ALI mice. Additionally, 1,4-GL corrected the APAP-induced gut microbiota imbalance, increased the abundance of Lactobacillus, and elevated hepatic levels of isoleucine, glutamine, and nicotinic acid. Correlation analyses between gut microbiota and liver metabolites revealed that glutamine and nicotinic acid were significantly positively correlated with Firmicutes and Lactobacillus, while showing a significant negative correlation with Lachnoclostridium. Lactobacillus was identified as a key beneficial bacterium, whereas Lachnoclostridium was associated with increased disease severity.Our findings suggest that 1,4-GL exerts a beneficial regulatory effect on APAP-induced ALI associated with Lactobacillus-Glutamine and Nicotinic Acid Pathways.