NAD precursors cycle between host tissues and the gut microbiome
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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.
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Intravenously injected NAM cycled between the host tissue and the gut microbiome.
“Intravenously injected NAM cycled between the host tissue and the gut microbiome.”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [24]
Gut microbiota also influenced host NAD+ metabolism by deamidating NAM coming across the blood vessels.
“The gut microbiota also influenced host NAD+ metabolism by deamidating NAM coming across the blood vessels (24).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [24]
The gut microbiota is essentially involved in the host NAD+ metabolism network.
“Recent studies indicated that the gut microbiota is essentially involved in the host NAD+ metabolism network (22–24).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [24]
Orally administered NR was degraded into NAM and then converted to NA by gut microbiota before absorption.
“However, subsequent studies and our current study demonstrated that orally administered NR was degraded into NAM and then converted to NA by gut microbiota before absorption (22–24).”
From Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD <sup>+</sup> synthesis via enterohepatic circulation (2025) · cites this paper as [24]
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Gaut, Z. N., & Solomon, H. M. (1971) · Biochemical Pharmacology · doi:10.1016/0006-2952(71)90202-4 · Cited by 23 · see citing works
Scalable syntheses of traceable ribosylated NAD + precursors
Makarov, M. V., Harris, N. W., Rodrigues, M. D. S., & Migaud, M. E. (2019) · Organic & Biomolecular Chemistry · doi:10.1039/c9ob01981b · Cited by 20 · see citing works
Self-citationElliott, G. C., & RECHSTEINER, M. C. (1982) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(82)91348-1 · Cited by 18 · see citing works
Reiche, I., Westphal, S., Martens‐Lobenhoffer, J., Tröger, U., Luley, C. H., & Bode‐Böger, S. M. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq344 · Cited by 18 · see citing works
Ibrahim, G. R., Shah, I., Gariballa, S., Yasin, J., Barker, J., & Ashraf, S. M. (2020) · Molecules · doi:10.3390/molecules25173932 · Cited by 16 · see citing works
Menon, R. M., Tolbert, D. S., & Cefali, E. A. (2007) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.555 · Cited by 10 · see citing works
Nicotinamide Deficiency in Primary Open-Angle GlaucomaPreprint
Nzoughet, J. K., de la Barca, J. M. C., Guehlouz, K., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/571638 · Cited by 8 · see citing works
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
Yaku, K., Palikhe, S., Iqbal, T., Hayat, F., Watanabe, Y., Fujisaka, S., Izumi, H., Yoshida, T., Karim, M., Uchida, H., et al. (2025) · Science Advances · doi:10.1126/sciadv.adr1538 · Cited by 40 · see citing works
Self-citation
- Authors
- Chellappa, K., McReynolds, M. R., Lu, W., Zeng, X., Makarov, M., Hayat, F., Mukherjee, S., Bhat, Y. R., Lingala, S. R., Shima, R. T., Descamps, H. C., Cox, T., Ji, L., Jankowski, C., Chu, Q., Davidson, S. M., Thaiss, C. A., Migaud, M. E., Rabinowitz, J. D., & Baur, J. A.
- Affiliations
- University of Pennsylvania (US)
- Princeton University (US)
- USA Mitchell Cancer Institute (US)
- Corresponding author
- Rabinowitz, Joshua D.
- Baur, Joseph A.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 34
- Issue
- 12
- Pages
- 1947-1959.e5
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC9825113
- OpenAlex
- W4311572757
- Cited by
- 146
- References
- 88
- Citations by year
- 2026: 39 · 2025: 50 · 2024: 33 · 2023: 21 · 2022: 3
- FWCI
- 15.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIDDK (R01DK098656)
- Burroughs Wellcome Fund
- Rutgers Cancer Institute of New Jersey
- Diabetes Research Center (P30-DK19525, S10-OD025098)
- Howard Hughes Medical Institute
- National Institutes of Health (CA211437, DP1DK113643, R01AG043483)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- NAD+ synthesis, nicotinamide, nicotinic acid, nicotinamide riboside, gut microbiota, isotope tracing, redox cofactors
- MeSH terms
- Animals, Mammals, NAD, Niacin, Niacinamide, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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