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Study · Measured the body's own peptide · 2022

9 results

Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia.

ElMokh O, Matsumoto S, Biniecka P, Bellotti A, Schaeuble K, Piacente F, Gallart-Ayala H, Ivanisevic J, Stamenkovic I, Nencioni A, Nahimana A, Duchosal MA

Cell death & disease8 Apr 2022Cited by 16 (Europe PMC)

PMID35396381 (opens in a new tab)PMCIDPMC8993809 (opens in a new tab)DOI10.1038/s41419-022-04763-3 (opens in a new tab)PepBankPUB-35396381
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Summary

Most cancer cells have high need for nicotinamide adenine dinucleotide (NAD+) to sustain their survival. This led to the development of inhibitors of nicotinamide (NAM) phosphoribosyltransferase (NAMPT), the rate-limiting NAD+ biosynthesis enzyme from NAM. Such inhibitors kill cancer cells in preclinical studies but failed in clinical ones. To identify parameters that could negatively affect the therapeutic efficacy of NAMPT inhibitors and propose therapeutic strategies to circumvent such failure, we performed metabolomics analyses in tumor environment and explored the effect of the interaction between microbiota and cancer cells. Here we show that tumor environment enriched in vitamin B3 (NAM) or nicotinic acid (NA) significantly lowers the anti-tumor efficacy of APO866, a prototypic NAMPT inhibitor. Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA. This leads to the rescue from NAD depletion, prevents reactive oxygen species production, preserves mitochondrial integrity, blunts ATP depletion, and protects cancer cells from death.Our data in an in vivo preclinical model reveal that antibiotic therapy down-modulating gut microbiota can restore the anti-cancer efficacy of APO866. Alternatively, NAphosphoribosyltransferase inhibition may restore anti-cancer activity of NAMPT inhibitors in the presence of gut microbiota and of NAM in the diet.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

No result from this study comes from a test of the peptide.

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 01LabEndogenous levelIn vitro (cells)Mechanism

    Bacterial conversion of NAM to NA fueled an alternative natural NAD synthesis pathway.

    In plain wordsIn lab tests, bacteria fueled an alternative pathway that makes natural NAD.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    IncreaseAlternative NAD synthesis
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Receptor activity and mechanism · Cancer

    Source sentences

    Summary
    Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA.

    This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.

  2. 02LabEndogenous levelIn vitro (cells)Mechanism

    In cancer cells, bacterial NAM conversion rescued natural NAD from depletion.

    In plain wordsIn cells, bacterial NAM conversion prevented depletion of the body's own NAD.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    IncreaseNAD depletion rescue
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Mitochondrial function · Cancer

    Source sentences

    Summary
    This leads to the rescue from NAD depletion
    1 context sentence
    Summary · context
    Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA.

    This result measures the body's own NAD+ (nicotinamide adenine dinucleotide). Nobody was given the peptide. It is not evidence about taking it.

Studies that did not test the peptide alone7

In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

  1. 03AnimalNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneAnimal study (in vivo)Efficacy outcome

    In a preclinical animal model, antibiotics that reduced gut microbiota restored the anticancer efficacy of NAD synthesis inhibitor APO866.

    In plain wordsIn animals, antibiotics that reduced gut microbes restored the anticancer effect of NAD synthesis inhibitor APO866.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    IncreaseAPO866 anticancer efficacy after antibiotics
    Study

    n: not reported in source

    In vivo preclinical cancer model
    Outcome group
    Tumor growth · Cancer

    Source sentences

    Summary
    Our data in an in vivo preclinical model reveal that antibiotic therapy down-modulating gut microbiota can restore the anti-cancer efficacy of APO866.

    In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

  2. 04LabNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneIn vitro (cells)Efficacy outcome

    In the tumor environment, vitamin B3 enrichment reduced the antitumor efficacy of the NAD synthesis inhibitor APO866.

    In plain wordsIn lab tests, vitamin B3 enrichment reduced the anticancer effect of the NAD synthesis inhibitor APO866.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    DecreaseAPO866 antitumor efficacy
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Tumor growth · Cancer

    Source sentences

    Summary
    Here we show that tumor environment enriched in vitamin B3 (NAM) or nicotinic acid (NA) significantly lowers the anti-tumor efficacy of APO866, a prototypic NAMPT inhibitor.

    In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

  3. 05LabNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneIn vitro (cells)Efficacy outcome

    In the tumor environment, nicotinic acid enrichment reduced the antitumor efficacy of the NAD synthesis inhibitor APO866.

    In plain wordsIn lab tests, nicotinic acid enrichment reduced the anticancer effect of the NAD synthesis inhibitor APO866.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    DecreaseAPO866 antitumor efficacy with nicotinic acid
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Tumor growth · Cancer

    Source sentences

    Summary
    Here we show that tumor environment enriched in vitamin B3 (NAM) or nicotinic acid (NA) significantly lowers the anti-tumor efficacy of APO866, a prototypic NAMPT inhibitor.

    In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

  4. 06LabNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneIn vitro (cells)Mechanism

    In cancer cells, bacterial support of alternative NAD synthesis prevented reactive oxygen species production.

    In plain wordsIn cells, bacterial support of NAD synthesis prevented reactive oxygen species production.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    DecreaseReactive oxygen species production
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Mitochondrial function · Cancer

    Source sentences

    Summary
    This leads to the rescue from NAD depletion, prevents reactive oxygen species production, preserves mitochondrial integrity, blunts ATP depletion, and protects cancer cells from death.
    1 context sentence
    Summary · context
    Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA.

    In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

  5. 07LabNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneIn vitro (cells)Mechanism

    In cancer cells, bacterial support of alternative NAD synthesis preserved mitochondrial integrity.

    In plain wordsIn cells, bacterial support of NAD synthesis preserved mitochondrial integrity.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    IncreaseMitochondrial integrity
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Mitochondrial function · Cancer

    Source sentences

    Summary
    This leads to the rescue from NAD depletion, prevents reactive oxygen species production, preserves mitochondrial integrity, blunts ATP depletion, and protects cancer cells from death.
    1 context sentence
    Summary · context
    Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA.

    In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

  6. 08LabNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneIn vitro (cells)Mechanism

    In cancer cells, bacterial support of alternative NAD synthesis blunted ATP depletion.

    In plain wordsIn cells, bacterial support of NAD synthesis reduced ATP depletion.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    DecreaseATP depletion
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Mitochondrial function · Cancer

    Source sentences

    Summary
    This leads to the rescue from NAD depletion, prevents reactive oxygen species production, preserves mitochondrial integrity, blunts ATP depletion, and protects cancer cells from death.
    1 context sentence
    Summary · context
    Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA.

    In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

  7. 09LabNot a test of NAD+ (nicotinamide adenine dinucleotide) aloneIn vitro (cells)Efficacy outcome

    In cancer cells, bacterial support of alternative NAD synthesis protected cells from death.

    In plain wordsIn cells, bacterial support of NAD synthesis protected cancer cells from death.

    Peptide
    NAD+ (nicotinamide adenine dinucleotide)
    Outcome
    DecreaseCancer cell death
    Study

    n: not reported in source

    Cancer cells
    Outcome group
    Tumor growth · Cancer

    Source sentences

    Summary
    This leads to the rescue from NAD depletion, prevents reactive oxygen species production, preserves mitochondrial integrity, blunts ATP depletion, and protects cancer cells from death.
    1 context sentence
    Summary · context
    Additionally, bacteria (from the gut, or in the medium) can convert NAM into NA and thus fuel an alternative NAD synthesis pathway through NA.

    In this study, NAD+ (nicotinamide adenine dinucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NAD+ (nicotinamide adenine dinucleotide).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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