In silico insights into potential gut microbial modulation of NAD+ metabolism and longevity.

Autor: Salekeen R; Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh., Siam MHB; Department of Microbiology, Faculty of Biological Science, University of Dhaka, Dhaka, Bangladesh., Sharif DI; Department of Genetic Engineering and Biotechnology, Faculty of Life and Earth Sciences, Jagannath University, Dhaka, Bangladesh., Lustgarten MS; Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, Massachusetts, USA., Billah MM; Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh., Islam KMD; Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2021 Dec; Vol. 35 (12), pp. e22925. Date of Electronic Publication: 2021 Sep 27.
DOI: 10.1002/jbt.22925
Abstrakt: Recent evidence has prompted the notion of gut-microbial signatures as an indirect marker of aging and aging-associated decline in humans. However, the underlying host-symbiont molecular interactions contributing to these signatures remain poorly understood. In this study, we address this gap using cheminformatic analyses to elucidate potential gut microbial metabolites that may perturb the longevity-associated NAD+ metabolic network. In silico ADMET, KEGG interaction analysis, molecular docking, molecular dynamics simulation, and molecular mechanics calculation predict a large number of safe and bioavailable microbial metabolites to be direct and/or indirect activators of NAD+-dependent sirtuin proteins. Our simulation results suggest dihydropteroate, phenylpyruvic acid, indole-3-propionic acid, phenyllactic acid, all-trans-retinoic acid, and multiple deoxy-, methyl-, and cyclic nucleotides from intestinal microbiota as the best-performing regulators of NAD+ metabolism. Retracing these molecules to their source microorganisms also suggest commensal Escherichia, Bacteroides, Bifidobacteria, and Lactobacilli to be associated with the highest number of pro-longevity metabolites. These findings from our early-stage study, therefore, provide an informatics-based context for previous evidence in the area and grant novel insights for future clinical investigation intersecting anti-aging drug discovery, probiotics, and gut microbial signatures.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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