NAD precursors cycle between host tissues and the gut microbiome

Karthikeyani Chellappa, Melanie R. McReynolds, Wenyun Lu, Xianfeng Zeng, Mikhail Makarov, Faisal Hayat, Sarmistha Mukherjee, Yashaswini R. Bhat, Siddharth R. Lingala, Rafaella T. Shima, Hélène C. Descamps, Timothy Cox, Lixin Ji, Connor Jankowski, Qingwei Chu, Shawn M. Davidson, Christoph A. Thaiss, Marie E. Migaud, Joshua D. Rabinowitz, Joseph A. Baur

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1947-1959.e5
JournalCell Metabolism
Volume34
Issue number12
DOIs
StatePublished - Dec 6 2022

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Keywords

  • flux
  • gastrointestinal
  • microbe
  • microbiome
  • mononucleotide
  • NAD
  • niacin
  • nicotinamide
  • nicotinic acid
  • riboside

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