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Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans.

ABSTRACT: The gut microbiota impacts systemic levels of multiple metabolites including NAD⁺ precursors through diverse pathways. Nicotinamide riboside (NR) is an NAD⁺ precursor capable of regulating mammalian cellular metabolism. Some bacterial families express the NR-specific transporter, PnuC. We hypothesized that dietary NR supplementation would modify the gut microbiota across intestinal sections. We determined the effects of 12 weeks of NR supplementation on the microbiota composition of intestinal segments of high-fat diet-fed (HFD) rats. We also explored the effects of 12 weeks of NR supplementation on the gut microbiota in humans and mice. In rats, NR reduced fat mass and tended to decrease body weight. Interestingly, NR increased fat and energy absorption but only in HFD-fed rats. Moreover, 16S rRNA gene sequencing analysis of intestinal and fecal samples revealed an increased abundance of species within Erysipelotrichaceae and Ruminococcaceae families in response to NR. PnuC-positive bacterial strains within these families showed an increased growth rate when supplemented with NR. The abundance of species within the Lachnospiraceae family decreased in response to HFD irrespective of NR. Alpha and beta diversity and bacterial composition of the human fecal microbiota were unaltered by NR, but in mice, the fecal abundance of species within Lachnospiraceae increased while abundances of Parasutterella and Bacteroides dorei species decreased in response to NR. In conclusion, oral NR altered the gut microbiota in rats and mice, but not in humans. In addition, NR attenuated body fat mass gain in rats, and increased fat and energy absorption in the HFD context.

SUBMITTER: Peluso AA

PROVIDER: S-EPMC10070358 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans.

Peluso A Augusto AA Lundgaard Agnete T AT Babaei Parizad P Mousovich-Neto Felippe F Rocha Andréa L AL Damgaard Mads V MV Bak Emilie G EG Gnanasekaran Thiyagarajan T Dollerup Ole L OL Trammell Samuel A J SAJ Nielsen Thomas S TS Kern Timo T Abild Caroline B CB Sulek Karolina K Ma Tao T Gerhart-Hines Zach Z Gillum Matthew P MP Arumugam Manimozhiyan M Ørskov Cathrine C McCloskey Douglas D Jessen Niels N Herrgård Markus J MJ Mori Marcelo A S MAS Treebak Jonas T JT

npj aging 20230403 1

The gut microbiota impacts systemic levels of multiple metabolites including NAD<sup>+</sup> precursors through diverse pathways. Nicotinamide riboside (NR) is an NAD<sup>+</sup> precursor capable of regulating mammalian cellular metabolism. Some bacterial families express the NR-specific transporter, PnuC. We hypothesized that dietary NR supplementation would modify the gut microbiota across intestinal sections. We determined the effects of 12 weeks of NR supplementation on the microbiota compo ...[more]

PMID: 37012386

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Project description:BackgroundNicotinamide riboside (NR) is an NAD+ precursor that boosts cellular NAD+ concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation.ObjectivesWe aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health parameters in overweight and obese volunteers.MethodsA randomized, double-blinded, placebo-controlled, crossover intervention study was conducted in 13 healthy overweight or obese men and women. Participants received 6 wk NR (1000 mg/d) and placebo supplementation, followed by broad metabolic phenotyping, including hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy, muscle biopsies, and assessment of ex vivo mitochondrial function and in vivo energy metabolism.ResultsMarkers of increased NAD+ synthesis-nicotinic acid adenine dinucleotide and methyl nicotinamide-were elevated in skeletal muscle after NR compared with placebo. NR increased body fat-free mass (62.65% ± 2.49% compared with 61.32% ± 2.58% in NR and placebo, respectively; change: 1.34% ± 0.50%, P = 0.02) and increased sleeping metabolic rate. Interestingly, acetylcarnitine concentrations in skeletal muscle were increased upon NR (4558 ± 749 compared with 3025 ± 316 pmol/mg dry weight in NR and placebo, respectively; change: 1533 ± 683 pmol/mg dry weight, P = 0.04) and the capacity to form acetylcarnitine upon exercise was higher in NR than in placebo (2.99 ± 0.30 compared with 2.40 ± 0.33 mmol/kg wet weight; change: 0.53 ± 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism.ConclusionsNR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD+ metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed.This trial was registered at clinicaltrials.gov as NCT02835664.

Project description:IntroductionAge-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.MethodsThe primary efficacy outcome was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Secondary outcomes included plasma phosphorylated tau 217 (pTau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Exploratory outcomes included Lumosity gameplay (z-scores) for cognition and step counts from wearables. Mixed model for repeated measures was used for between-group comparisons; paired t-tests were used for within-individual comparisons.ResultsForty-six participants aged over 55 were randomized to NR-PBO or PBO-NR groups; 41 completed baseline visits, and 37 completed the trial. NR supplementation was safe and well tolerated with no differences in adverse events reported between NR and PBO treatment phases. For the between-group comparison, there was a 7% reduction in pTau217 concentrations after taking NR, while an 18% increase with PBO (p = 0.02). No significant between-group differences were observed for RBANS, other plasma biomarkers(GFAP and NfL), Lumosity gameplay scores or step counts. For the within-individual comparison, pTau217 concentrations significantly decreased during the NR phase compared to the PBO (p = 0.02), while step counts significantly increased during the NR phase than PBO (p = 0.04).DiscussionEight weeks NR supplementation is safe and lowered pTau217 concentrations but did not alter cognition as measured by conventional or novel digital assessments. Further research is warranted to validate NR's efficacy in altering pathological brain aging processes.HighlightsThe integrated study design combines a two-arm parallel trial with a crossover phase, offering the opportunity to enhance sample size for within-individual analysis and assess carryover effects.NR is safe but did not alter cognition as measured by multi-modal assessments in SCD/MCI.For between-group comparison, pTau217 levels decreased with NR and increased with PBO at 8-week follow-up.For within-individual comparison, step counts increased after NR and decreased after PBO.A larger, longer study with pharmacodynamic and pathophysiological biomarkers is needed to assess NR's disease-modifying effects.

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Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans.

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Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans.

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