The (amide-)N-methylnicotinamide is a microbe-derived NAD

Jiangmeng Han, Jayson M Antonio, Jagannatham Naidu Bhupana, Garam Choi, Jiaxing Yang, Eric Chiles, Yan Tong, Mohamed Asik Rajmohamed, Hung-Ting Wu, Dahui Wang, Vik Meadows, Nicolas Lapaque, Jean-Pierre Etchegaray, Rafal Filip, Ta-Chiang Liu, Pawel R Kiela, Nicholas Bessman, Ronaldo P Ferraris, Ching-On Wong, Xiaoyang Su, Nan Gao

Department of Biological Sciences, Rutgers University, Newark, New Jersey, USA. · pubmed

Paper

Abstract

Nicotinamide Adenine Dinucleotide (NAD) is a critical cellular coenzyme whose decline associates with various chronic and inflammatory diseases. Improved NAD restoration may reduce disease risks and extend healthy lifespan. We report here that certain commensal bacteria including specific probiotic species produce (amide-)N-methylnicotinamide (N-MNA), which is a structural isomer of methylnicotinamide, a nicotinamide degradative metabolite. Patients with gut dysbiosis and inflammation show reduced stool N-MNA. Stable isotope tracing revealed that N-MNA can be rapidly taken up and incorporated into NAD redox reactions by intestinal epithelial cells (IECs) and non-IECs of fruit fly, mouse, and human. Genetic and pharmacological analyses suggest that N-MNA is converted to NAD

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that commensal bacteria produce (amide-)N-methylnicotinamide (N-MNA), a metabolite that is rapidly taken up by intestinal cells and converted into NAD, thereby linking gut microbiome composition directly to host NAD+ homeostasis. This is relevant to longevity because NAD+ decline is a fundamental hallmark of aging, and identifying a microbial source for a novel NAD precursor suggests a potential mechanism by which the microbiome influences systemic metabolic aging and offers a new avenue for NAD+ restoration therapies.

Author of this paper? Send a correction.