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Salekeen R, Siam MHB, Sharif DI, et al. In silico insights into potential gut microbial modulation of NAD+ metabolism and longevity. J Biochem Mol Toxicol. 2021;e22925doi: 10.1002/jbt.22925.
Salekeen, R., Siam, M. H. B., Sharif, D. I., Lustgarten, M. S., Billah, M. M., & Islam, K. M. D. (2021). In silico insights into potential gut microbial modulation of NAD+ metabolism and longevity. Journal of biochemical and molecular toxicology, e22925. https://doi.org/10.1002/jbt.22925
Salekeen, Rahagir, et al. "In silico insights into potential gut microbial modulation of NAD+ metabolism and longevity." Journal of biochemical and molecular toxicology vol. (2021): e22925. doi: https://doi.org/10.1002/jbt.22925
Salekeen R, Siam MHB, Sharif DI, Lustgarten MS, Billah MM, Islam KMD. In silico insights into potential gut microbial modulation of NAD+ metabolism and longevity. J Biochem Mol Toxicol. 2021 Sep 27;e22925. doi: 10.1002/jbt.22925. Epub 2021 Sep 27. PMID: 34580953.
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J Biochem Mol Toxicol. 2021 Sep 27;e22925. doi: 10.1002/jbt.22925. Epub 2021 Sep 27.

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

Journal of biochemical and molecular toxicology

Rahagir Salekeen, Md Hasanul Banna Siam, Dilara Islam Sharif, Michael S Lustgarten, Md Morsaline Billah, Kazi Mohammed Didarul Islam

Affiliations

  1. Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna, Bangladesh.
  2. Department of Microbiology, Faculty of Biological Science, University of Dhaka, Dhaka, Bangladesh.
  3. Department of Genetic Engineering and Biotechnology, Faculty of Life and Earth Sciences, Jagannath University, Dhaka, Bangladesh.
  4. Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center, Tufts University, Boston, Massachusetts, USA.

PMID: 34580953 DOI: 10.1002/jbt.22925

Abstract

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.

Keywords: antiaging; bioinformatics; cheminformatics; drug discovery; intestinal microbiota; sirtuins

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