The (amide-)N-methylnicotinamide is a microbe-derived NAD + precursor that drives gut stem cell renewal
Year: 2026
Type: article
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 + via the Preiss-Handler pathway, independent of the salvage pathway. Cell-type-specific ablation or overexpression of SIRT1, an NAD-consuming enzyme, in Drosophila , along with intestinal stem cell (ISC) lineage tracing in mice revealed that systemic N-MNA supplementation promotes ISC regeneration and gut epithelial repair. Compared to known NAD precursors, N-MNA brings a methyl group into host cells, representing a class of microbe-derived NAD precursor that stimulates the tissue regenerative power.
Source: Science Advances
Authors: 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
Institutions: Rutgers, The State University of New Jersey, Rutgers Health, Rutgers New Jersey Medical School, Rutgers Cancer Institute, Washington University in St. Louis, AgroParisTech, Université Paris-Saclay, Microbiologie de l’alimentation au service de la santé, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, MetaGenoPolis, University of Rzeszów, University of Arizona
Language: English
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: National Science Foundation, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Complementary and Integrative Health
Awards: Cell differentiation regulates intestinal tight junctions, Mucosal modulation by LGG and R. gnavus specific tryptophan metabolites, Intestinal lysozyme controls mucosal immune response to microbiota, EAGER: Integration and analysis of high-dimensional dataset, Cancer Center Support Grant, Paneth cell heterogeneity in infection and inflammation, Mechanism of intestinal TET3-mediated DNA oxidation and transcriptional regulation, Role of TTYH1 in mobilizing lipids and ApoE in glia: Implications for brain aging and neurodegeneration, Investigating the Role of SLC45A4 in GABA Metabolism, The role of local iron homeostasis in inflammatory bowel disease, PARP1 and PARylation as novel effectors of gut inflammation, TET-mediated DNA oxidations in mucosal innate defense
OpenAlex ID: W7225432606