NAD+ and its possible role in gut microbiota: Insights on the mechanisms by which gut microbes influence host metabolism

Abstract

Nicotinamide adenine dinucleotide (NAD⁺) is an enzyme cofactor, co-substrate, and redox factor in all living cells and is necessary for maintaining cell metabolism. It has been shown that appropriate supplementation of NAD⁺ precursors or inhibition of NAD⁺-depleting enzymes can promote mitochondrial oxidative phosphorylation and improve host energy utilization efficiency. In addition, increasing evidence indicates that the gut microbiota plays a pivotal role in host metabolism. Theoretically, there should be a close correlation among NAD⁺, gut microbiota, and host metabolism; however, the information is limited. In this review, we summarize the metabolic process of NAD⁺ and its impact on host metabolism, the link between gut microbiota and host metabolism, as well as the potential effects of NAD⁺ on microbial metabolism, providing a new perspective on the interaction between gut microbiota and host metabolism.

Keywords: Gut microbiota; Host metabolism; Metabolic diseases; NAD+.

Fig. 1

NAD⁺ metabolic pathway in mammalian cells and gut microbes. ARTs = adenosine diphosphate-ribose transferases; NA = nicotinic acid; NAD = nicotinamide adenine dinucleotide; NADK = NAD kinase; NADP = nicotinamide adenine dinucleotide phosphate; NAM = nicotinamide; NAMN = nicotinic acid mononucleotide; NAMPT = nicotinamide phosphoribosyltransferase; NMN = nicotinamide mononucleotide; NMNAT = nicotinamide mononucleotide adenylyltransferase; NNMT = nicotinamide N-methyltransferase; NRK = nicotinamide ribose kinases; NR = nicotinamide ribose; NPRT = nicotinic acid phosphoribosyltransferase; MNA = 1-methylnicotinamide; PncA = nicotinamidase; PNP = purine nucleoside phosphorylase; QA = quinolinic acid; QPRT = quinolinic acid phosphoribosyltransferase; SIRTs = sirtuins; SARM1 = sterile alpha and Toll/interleukin-1 receptor motif-containing 1.

Fig. 2

The roles of NAD⁺ on the host metabolism and its speculated regulatory effects on gut microbiota. AMPK = AMP-activated protein kinase; BA = bile acids; FOXO = forkhead box O; NAD⁺ = nicotinamide adenine dinucleotide; PGC1α = peroxisome proliferator receptor gamma coactivator alpha; SIRT1 = sirtuin1; SCFA = short-chain fatty acids; TMA = trimethylamine.