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.

NAD+ Precursors and Intestinal Inflammation: Therapeutic Insights Involving Gut Microbiota

“…Furthermore, NAM also restored the reduction in valeric acid in mice with DSS-induced chronic colitis. Consistent with another report [21], fecal SCFA levels did not differ among groups, except for valeric acid, which was restored after NAM treatment. Similar results were reported in another mouse model of mild colitis [132].…”

“…In this same study, NR intake in mice also influenced the gut microbiota after 12 weeks of treatment, but the observed changes differ from those seen in rat feces [21]. In mice, NR intake increased the relative proportion of Lachnospiraceae (Firmicutes phylum) species.…”

“…In contrast to rats and mice, in humans, NR did not modulate the alpha and beta diversity and bacterial composition of fecal microbiota and was unlikely to influence bacterial species capable of synthesizing NAD+ from specific precursors [21]. Nonetheless, some benefits on intestinal inflammation could be inferred from favorable changes in fecal composition of microbiota, and therefore future studies evaluating the therapeutic potential of NR in humans may be required.…”

“…NR administration also influences intestinal microbiota [21,134,135]; however, its effects appear to be species-specific [21]. A study found that dietary supplementation of NR induced changes in the composition of gut microbiota in both rats and mice, favoring bacterial species capable of synthesizing NAD+ from specific precursors.…”

“…Moreover, the intestinal microbiota profoundly impacts host NAD+ metabolism by promoting host NAD+ synthesis [10]. Conversely, recent research supports the notion that vitamin B3-related supplements can have a beneficial effect on intestinal permeability [18] and inflammation [19][20][21] by modulating the composition of intestinal microbiota.…”