TY - JOUR
T1 - NAD precursors cycle between host tissues and the gut microbiome
AU - Chellappa, Karthikeyani
AU - McReynolds, Melanie R.
AU - Lu, Wenyun
AU - Zeng, Xianfeng
AU - Makarov, Mikhail
AU - Hayat, Faisal
AU - Mukherjee, Sarmistha
AU - Bhat, Yashaswini R.
AU - Lingala, Siddharth R.
AU - Shima, Rafaella T.
AU - Descamps, Hélène C.
AU - Cox, Timothy
AU - Ji, Lixin
AU - Jankowski, Connor
AU - Chu, Qingwei
AU - Davidson, Shawn M.
AU - Thaiss, Christoph A.
AU - Migaud, Marie E.
AU - Rabinowitz, Joshua D.
AU - Baur, Joseph A.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/12/6
Y1 - 2022/12/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cmet.2022.11.004
DO - 10.1016/j.cmet.2022.11.004
M3 - Article
C2 - 36476934
AN - SCOPUS:85143528388
SN - 1550-4131
VL - 34
SP - 1947-1959.e5
JO - Cell Metabolism
JF - Cell Metabolism
IS - 12
ER -