1. Academic Validation
  2. Bacterial PncA improves diet-induced NAFLD in mice by enabling the transition from nicotinamide to nicotinic acid

Bacterial PncA improves diet-induced NAFLD in mice by enabling the transition from nicotinamide to nicotinic acid

  • Commun Biol. 2023 Mar 2;6(1):235. doi: 10.1038/s42003-023-04613-8.
Shengyu Feng 1 Liuling Guo 1 Hao Wang 1 Shanshan Yang 1 Hailiang Liu 2 3
Affiliations

Affiliations

  • 1 Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, 200123, Shanghai, China.
  • 2 Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, 200123, Shanghai, China. hailiang_1111@tongji.edu.cn.
  • 3 Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, 832003, Shihezi, China. hailiang_1111@tongji.edu.cn.
Abstract

Nicotinamide adenine dinucleotide (NAD+) is crucial for energy metabolism, oxidative stress, DNA damage repair, longevity regulation, and several signaling processes. To date, several NAD+ synthesis pathways have been found in microbiota and mammals, but the potential relationship between gut microbiota and their hosts in regulating NAD+ homeostasis remains largely unknown. Here, we showed that an analog of the first-line tuberculosis drug pyrazinamide, which is converted by nicotinamidase/pyrazinamidase (PncA) to its active form, affected NAD+ level in the intestines and liver of mice and disrupted the homeostasis of gut microbiota. Furthermore, by overexpressing modified PncA of Escherichia coli, NAD+ levels in mouse liver were significantly increased, and diet-induced non-alcoholic fatty liver disease (NAFLD) was ameliorated in mice. Overall, the PncA gene in microbiota plays an important role in regulating NAD+ synthesis in the host, thereby providing a potential target for modulating host NAD+ level.

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