Identification of enterohepatic circulation as a metabolic pathway for nicotinamide riboside and nicotinamide mononucleotide, nutrients considered to have anti-aging properties.
The research group of Prof. Takashi Nakagawa and lecturer Keisuke Yaku (Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama) recently identified enterohepatic circulation as a novel metabolic pathway for nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), in which gut microbiota play a crucial role.
NR and NMN are precursors of nicotinamide adenine dinucleotide (NAD?), a key molecule involved in energy production, protein post-translational modification, and DNA repair. NAD? levels decline with age, leading to decreased physiological function. Restoration of NAD? levels using NR and NMN has been widely explored as a strategy to counteract aging-related metabolic and physical deterioration. Recently, the involvement of gut microbiota in NAD? metabolism has attracted increasing attention. However, the mechanisms by which gut microbiota regulate NR and NMN metabolism remain poorly understood.
Prof. Nakagawa research group analyzed the metabolic fate of NR and NMN using mass spectrometry-based NAD? metabolomics, a method they had previously established. They found that both NR and NMN are metabolized into nicotinic acid (NA) by gut microbiota following oral administration. Interestingly, NR and NMN were also metabolized in a microbiota-dependent manner after intravenous administration. As the underlying mechanism, they discovered that enterohepatic circulation regulates this process: intravenously injected NAD? precursors are secreted into bile, metabolized into NA by gut microbiota, and subsequently utilized for NAD? synthesis in the liver.
These findings highlight the critical role of gut microbiota in the metabolism of NAD? precursors and underscore the importance of considering microbiota interactions in future clinical research involving these compounds.
Original article information
Title
Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD+ synthesis via enterohepatic circulation
Authors
Keisuke Yaku, Sailesh Palikhe, Tooba Iqbal, Faisal Hayat, Yoshiyuki Watanabe, Shiho Fujisaka, Hironori Izumi, Tomoyuki Yoshida, Mariam Karim, Hitoshi Uchida, Allah Nawaz, Kazuyuki Tobe, Hisashi Mori, Marie E Migaud, Takashi Nakagawa
Journal
Science Advances. 2025 Mar 21;11(12):eadr1538.