Bacterial PncA improves diet-induced NAFLD in mice by enabling the transition from nicotinamide to nicotinic acid
Open accessAbstract
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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Most bacteria have a NAM deamidase, an enzyme that converts NAM into NA.
“Most bacteria have a NAM deamidase, an enzyme that converts NAM into NA.”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [28]
The Introduction (page unavailable) says bacterial PncA catalyzes the conversion of NAM to NA. The Results (page unavailable) describe PncA as highly conserved across different bacterial phyla, but do not establish that most bacterial species have it. (LLM, conf=0.82)
Experimental — accuracy not yet measuredGut microbiota deamidase converts NAM, NR, NMN, and NAD+ to their deamidated forms.
“have deamidase, which converts NAM, NR, NMN, and NAD+ to their deamidated forms (26–28).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [28]
The Introduction (page unavailable) says that gut-flora PncA deamidates NAM to nicotinic acid. The paper discusses NR, NMN, and NAD+ as NAD-related molecules, but the passages do not say that a gut-microbiota deamidase converts those three to their deamidated forms. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMammals do not have a homologous enzyme to NAM deamidase.
“However, mammals do not have a homologous enzyme (12, 25–28).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [28]
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“The increase of deamidated metabolites was unexpected because mammals, including humans and rodents, do not have deamidase, which converts NAM, NR, NMN, and NAD + to their deamidated forms ( 26 – 28 ).”
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- Authors
- Feng, S., Guo, L., Wang, H., Yang, S., & Liu, H.
- Affiliations
- Tongji University (CN)
- Shihezi University (CN)
- Corresponding author
- Liu, Hailiang
- Venue
- Communications Biology
- Published
- 2023-03-02
- Volume
- 6
- Issue
- 1
- Pages
- 235-235
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC9981684
- OpenAlex
- W4322768369
- Cited by
- 20
- References
- 49
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 1 · 2022: 1
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82271593)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- pncA, NAD+ homeostasis, non-alcoholic fatty liver disease, gut microbiota, pyrazinamide, nicotinamide, nicotinic acid, NAD+ synthesis, host-microbe interactions, Escherichia coli, diet-induced obesity
- MeSH terms
- Animals, Diet, Escherichia coli, Mammals, NAD, Niacin, Niacinamide, Non-alcoholic Fatty Liver Disease
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