@article{8cfbf08d668c423da1d1db3a728d119d,
title = "NAD precursors cycle between host tissues and the gut microbiome",
abstract = "Nicotinamide adenine dinucleotide (NAD) is an essential redox cofactor in mammals and microbes. Here we use isotope tracing to investigate the precursors supporting NAD synthesis in the gut microbiome of mice. We find that dietary NAD precursors are absorbed in the proximal part of the gastrointestinal tract and not available to microbes in the distal gut. Instead, circulating host nicotinamide enters the gut lumen and supports microbial NAD synthesis. The microbiome converts host-derived nicotinamide into nicotinic acid, which is used for NAD synthesis in host tissues and maintains circulating nicotinic acid levels even in the absence of dietary consumption. Moreover, the main route from oral nicotinamide riboside, a widely used nutraceutical, to host NAD is via conversion into nicotinic acid by the gut microbiome. Thus, we establish the capacity for circulating host micronutrients to feed the gut microbiome, and in turn be transformed in a manner that enhances host metabolic flexibility.",
keywords = "NAD, flux, gastrointestinal, microbe, microbiome, mononucleotide, niacin, nicotinamide, nicotinic acid, riboside",
author = "Karthikeyani Chellappa and McReynolds, {Melanie R.} and Wenyun Lu and Xianfeng Zeng and Mikhail Makarov and Faisal Hayat and Sarmistha Mukherjee and Bhat, {Yashaswini R.} and Lingala, {Siddharth R.} and Shima, {Rafaella T.} and Descamps, {H{\'e}l{\`e}ne C.} and Timothy Cox and Lixin Ji and Connor Jankowski and Qingwei Chu and Davidson, {Shawn M.} and Thaiss, {Christoph A.} and Migaud, {Marie E.} and Rabinowitz, {Joshua D.} and Baur, {Joseph A.}",
note = "Funding Information: This work was funded and supported by a Crohn{\textquoteright}s and Colitis Career Development Award to K.C.; the Howard Hughes Medical Institute and Burroughs Wellcome Fund via the PDEP and Hanna H. Gray Fellow Program awarded to M.R.M.; and NIH grants CA211437 to W.L., DP1DK113643 to J.D.R., and R01DK098656 and R01AG043483 to J.A.B. We acknowledge support from the Regional Metabolomics and Fluxomics Core and the Rodent Metabolic Phenotyping Core of the Penn Diabetes Research Center P30-DK19525 and S10-OD025098 , as well as the CINJ Cancer Center Support Grant, Rutgers Cancer Institute of New Jersey Metabolomics Shared Resource, supported, in part, with funding from NCI-CCSG P30CA072720-5923 . Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = dec,
day = "6",
doi = "10.1016/j.cmet.2022.11.004",
language = "English (US)",
volume = "34",
pages = "1947--1959.e5",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "12",
}