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Drawing of beneficial bacterial inside the intestine

At first, scientists worried that the gut microbiome might be degrading NAD precursors in unhelpful ways. But more recent research suggests that instead of just competing for NAD precursors, the. gut microbiome might be assisting with bioavailability. More remarkable still, NAD precursors may even be improving the condition of the gut microbiome that it can function better.

Here are the studies:

Nov 8, 2022

Liver - Gut Microbiome - NAFLD - Intestinal Barrier Dysfunction

International Journal of Molecular Sciences

Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors’ Combination

Quesada-Vazquez, Sergio


This specific combination of metabolic cofactors [including nicotinamide riboside] can reverse gut barrier disruption and microbiota dysbiosis contributing to the amelioration of NAFLD progression by modulating key players of the gut-liver axis.

Oct 11, 2022

NMN - Metabolism - Gut Microbiota - Bioavailability


Nicotinamide mononucleotide (NMN) deamidation by host-microbiome interactions

Kim, Lynn-Jee


Ablation of the microbiome by antibiotic treatment increases the uptake and conversion of orally delivered NMN into the NAD metabolome, and that isotope labelled NMN overwhelmingly presents in intestinal tissue in the form of NR. Contrary to the assumption that exogenous NMN treatment raises NAD+ levels solely through its direct incorporation into the NAD metabolome, we show that treatment with isotope labelled NMN increases the levels of endogenous, unlabelled NAD metabolites....Given this evidence for the decomposition of NMN into free Nam prior to its uptake, a key question for the field is why downstream precursors in NAD+ synthesis such as NMN and NR lead to different outcomes compared to Nam alone...

Apr 28, 2022

Muscle - Gut Microbiota - Stem Cells - Mitochondria - Obesity

Science Advances

Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota composition in a twin study

Lapatto, Helena


We aimed to determine whether long-term nicotinamide riboside (NR) supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twins from 22 BMI-discordant monozygotic pairs were supplemented with an escalating dose of NR (250-1000 mg/day) for 5 months ( entry NCT03951285). NR improved blood and tissue NAD+ metabolism, muscle mitochondrial number, myoblast differentiation and gut microbiota composition independent of BMI. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.

Apr 8, 2022

Cancer - Leukemia - Gut Microbiome

Cell Death & Disease

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

ElMokh, Oussama


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.

Mar 22, 2022

Gut Microbiota - Cancer

Frontiers in Molecular Biosciences

Interventions in Nicotinamide Adenine Dinucleotide Metabolism, the Intestinal Microbiota and Microcin Peptide Antimicrobials

Baquero, Fernando


New possibilities for employing NAD + boosting agents as modulators of the intestinal microbiota should be considered for fostering repopulation of microbiota after decontaminating antibiotic therapy...If certain pathogens increase in abundance, NAD boosting might favor beneficial organisms, particularly in combination with probiotics, prebiotics, or fecal transplantation...If the intestinal microbiota increases the effect of NAD boosting drugs, their concomitant use with antimicrobial agents should be prescribed only in patients where the presence of neoplastic disease can be ruled out.

Jan 25, 2022

Gut Microbiota - Obesity


Nicotinamide Riboside-Conditioned Microbiota Deflects High-Fat Diet-Induced Weight Gain in Mice

Lozada-Fernandez, Valery


...It is unknown how dietary supplementation of NR alters the microbiome and if those alterations contribute to deflection of weight gain. In this study, we fed C57BL/6J male mice a high-fat diet (HFD) supplemented with or without NR and performed a fecal material transfer (FMT) to establish a link between NR-conditioned microbiota and NR-induced deflection of weight gain...We also investigated the effects of NR on the microbiome by using metagenomics sequencing. We found that NR-treated mice displayed an altered gut microbial composition relative to controls and that fecal transplant resulted in a distinct functional metabolic profile characterized by enrichment of butyrate-producing Firmicutes...These findings suggest that microbial factors contribute to the beneficial effects of dietary NR supplementation, which may be useful to enhance the therapeutic effects of NR...

Jan 25, 2022

Metabolism - Gut Microbiome


Metabolic Disease, NAD Metabolism, Nicotinamide Riboside, and the Gut Microbiome: Connecting the Dots from the Gut to Physiology

Suave, Anthony


...The involvement of the gut microbiome as a factor in NR effects is linked to changes to the gut microbiome and its activity to transform NR and downstream catabolites. This commentary draws attention to these findings and focuses on some puzzling aspects of NAD+ boosters, exploring the still murky interactions between NAD+ metabolism, energy homeostasis, and the gut microbiome.

Nov 19, 2021

Metabolism - Bioavailability - Gut Microbiota

Cell Metabolism

NAD precursors cycle between host tissues and the gut microbiome

Chellappa, Karthikeyani


...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, NAD precursors cycle between the host and gut microbiome to maintain NAD homeostasis.

Nov 19, 2021

Metabolism - Bioavailability - Gut Microbiota

Nature Communications

BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities

Yaku, Keisuke


The present study demonstrated that orally administered NR increased NAD+ levels in a diphasic manner. First, in the early phase (within 1 h after administration), NR was directly taken up by the small intestine and utilized for NAD+ synthesis via the NR salvage pathway. In the late phase (~3 h after administration), NR increased NAD+ levels in a manner dependent on gut microbiota.

Mar 3, 2021

Metabolism - Bioavailability - Gut Microbiota

Cell Metabolism

Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway

Shats, Igor


In summary, through chemical screen, global and targeted metabolic analyses, and functional genetic and biochemical assays, we discovered that bacteria contribute to the deamidated NAD biosynthesis in host cells through a microbial nicotinamidase (PncA).

Dec 21, 2020

Gut Microbiota - Liver

Food Science and Nutrition

Effect of nicotinamide riboside on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice

Yu, Xioa


...This study aimed to explore the effects of nicotinamide riboside (NR) on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice. NR significantly improved liver histopathological damage and abnormal liver function... Therefore, NR supplementation has the potential to prevent Alcoholic Liver Disease (ALD), and its mechanism may be related to regulating lipid metabolism disorders and the gut microflora-bile acid axis.

Sep 1, 2020

Brain - Alzheimer's Disease - Gut Microbiota

Frontiers in Aging Neuroscience

Nicotinamide adenine dinucleotide supplementation drives gut microbiota variation in Alzheimer’s mouse model

Chu, Xixia


Alzheimer’s disease (AD) is the most common neurodegenerative disease. Growing evidence suggests an important role for gut dysbiosis and gut microbiota-host interactions in aging and neurodegeneration. Our previous works have demonstrated that supplementation with the nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide riboside (NR), reduced the brain features of AD, including neuroinflammation, deoxyribonucleic acid (DNA) damage, synaptic dysfunction, and cognitive impairment. However, the impact of NR administration on the intestinal microbiota of AD remains unknown. In this study, we investigated the relationship between gut microbiota and NR treatment in APP/PS1 transgenic (AD) mice. Compared with wild type (WT) mice, the gut microbiota diversity in AD mice was lower and the microbiota composition and enterotype were significantly different. Moreover, there were gender differences in gut microbiome between female and male AD mice. After supplementation with NR for 8 weeks, the decreased diversity and perturbated microbial compositions were normalized in AD mice. This included the species Oscillospira, Butyricicoccus, Desulfovibrio, Bifidobacterium, Olsenella, Adlercreutzia, Bacteroides, Akkermansia, and Lactobacillus. Our results indicate an interplay between NR and host-microbiota in APP/PS1 mice, suggesting that the effect of NR on gut dysbiosis may be an important component in its therapeutic functions in AD.

Mar 3, 2020

Gut Microbiota - Cancer

Cell Metabolism

Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway

Shats, Igor


Nicotinamide adenine dinucleotide (NAD), a cofactor for hundreds of metabolic reactions in all cell types, plays an essential role in metabolism, DNA repair, and aging. However, how NAD metabolism is impacted by the environment remains unclear. Here, we report an unexpected trans-kingdom cooperation between bacteria and mammalian cells wherein bacteria contribute to host NAD biosynthesis. Bacteria confer resistance to inhibitors of NAMPT, the rate-limiting enzyme in the amidated NAD salvage pathway, in cancer cells and xenograft tumors. Mechanistically, a microbial nicotinamidase (PncA) that converts nicotinamide to nicotinic acid, a precursor in the alternative deamidated NAD salvage pathway, is necessary and sufficient for this protective effect. Using stable isotope tracing and microbiota-depleted mice, we demonstrate that this bacteria-mediated deamidation contributes substantially to the NAD-boosting effect of oral nicotinamide and nicotinamide riboside supplementation in several tissues. Collectively, our findings reveal an important role of bacteria-enabled deamidated pathway in host NAD metabolism.

Dec 3, 2019

Gut Microbiota

Food & Function

Nicotinamide riboside alleviates alcohol-induced depression-like behaviours in C57BL/6J mice by altering the intestinal microbiota associated with microglial activation and BDNF expression

Yushan, Jiang


...Here, we investigated the effects of NR in the mouse model of alcohol-induced depression. Treatment with NR improved the alcohol-induced depressive behaviour in mice...Collectively, our findings show that NR dietary supplementation protects against alcohol-induced depression-like behaviours, possibly by altering the composition of the gut microbiota.

Dec 6, 2017

Diabetes - Gut Microbiome

Diabetes Care

Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans

Fangmann, Daniela


In humans in vivo, gut-targeted delayed-release NA but not NAM produced a significant increase in the abundance of Bacteroidetes. In the absence of systemic side effects, these favorable microbiome changes induced by microencapsulated delayed-release NA were associated with an improvement of biomarkers for systemic insulin sensitivity and metabolic inflammation. Targeted microbiome intervention by delayed-release NA might represent a future therapeutic option for prediabetes and type 2 diabetes.

NAD Research - Gut / Microbiome

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