4.8 Article

NAD precursors cycle between host tissues and the gut microbiome

Journal

CELL METABOLISM
Volume 34, Issue 12, Pages 1947-+

Publisher

CELL PRESS
DOI: 10.1016/j.cmet.2022.11.004

Keywords

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Funding

  1. Elysium Health
  2. Metro International Biotech
  3. Crohn's and Colitis Career Development Award
  4. Howard Hughes Medical Institute
  5. Burroughs Wellcome Fund via the PDEP
  6. Burroughs Wellcome Fund via Hanna H. Gray Fellow Program
  7. NIH [CA211437, DP1DK113643, R01DK098656, R01AG043483]
  8. Regional Metabolomics and Fluxomics Core of the Penn Diabetes Research Center [P30-DK19525, S10-OD025098]
  9. Rodent Metabolic Phenotyping Core of the Penn Diabetes Research Center [P30-DK19525, S10-OD025098]
  10. CINJ Cancer Center Support Grant
  11. Rutgers Cancer Institute of New Jersey Metabolomics Shared Resource
  12. NCI-CCSG [P30CA072720-5923]

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Nicotinamide adenine dinucleotide (NAD) is an essential cofactor in mammals and microbes. This study reveals the ability of host micronutrients to support NAD synthesis in the gut microbiome and enhance host metabolic flexibility.
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 sup-ports 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 nu-traceutical, 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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