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

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.

• Authors: Shengyu Feng, Liuling Guo, Hao Wang, Shanshan Yang, Hailiang Liu
• Journal: Communications biology (Commun Biol) Vol. 6 Issue 1 Pg. 235 (03 02 2023) ISSN: 2399-3642 [Electronic] England
• PMID: 36864222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Niacin
• Niacinamide
• NAD

Topics

• Animals
• Niacin (pharmacology)
• Niacinamide (pharmacology)
• Non-alcoholic Fatty Liver Disease (etiology)
• NAD
• Diet
• Escherichia coli
• Mammals