Bacteria help mammals build a key energy molecule
Every cell, from bacteria to humans, contains an energy molecule called nicotinamide adenine dinucleotide (NAD), which plays an essential role in metabolism, DNA repair, and aging. Studies have shown that boosting NAD levels can slow the development of age-related ailments and reduce the progression and symptoms of some diseases. At the same time, decreasing NAD levels inside tumors is a promising approach to stopping cancer cell growth. Although the ways that NAD is synthesized in bacterial and human cells have been extensively — but separately — studied, it is unclear how bacterial cells can influence mammalian cells’ production of the molecule.
IRP researchers led by Xiaoling Li, Ph.D., discovered that bacteria found in the gut, as well as inside tumors, in mice contribute to the synthesis of mammalian NAD by supplying molecules necessary for its creation. This alternative synthesis process makes commercial dietary supplements that boost NAD levels more efficient. On the other hand, the research team discovered that this bacteria-mediated NAD synthesis also confers resistance against anti-cancer drugs that target conventional NAD production in tumors.
The discovery of this type of metabolic crosstalk between a mammalian host and the microbes living in its body links two NAD synthesis pathways in mammals and opens the door for new therapeutic approaches that target NAD metabolism by manipulating the bacteria found within the gut or a tumor.
Shats I, Williams JG, Liu J, Makarov MV, Wu X, Lih FB, Deterding LJ, Lim C, Xu X, Randall TA, Lee E, Li W, Fan W, Li JL, Sokolsky M, Kabanov AV, Li L, Migaud ME, Locasale JW, Li X. (2020). Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway. Cell Metab. Mar 3;31(3):564-579.e7. doi: 10.1016/j.cmet.2020.02.001.