Targeted Delivery of Persulfides to the Gut: Effects on the Microbiome
Kearsley M. Dillon
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorHolly A. Morrison
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorChadwick R. Powell
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorRyan J. Carrazzone
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorVeronica M. Ringel-Scaia
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorEthan W. Winckler
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorR. McAlister Council-Troche
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorCorresponding Author
Irving C. Allen
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorCorresponding Author
John B. Matson
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorKearsley M. Dillon
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorHolly A. Morrison
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorChadwick R. Powell
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorRyan J. Carrazzone
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorVeronica M. Ringel-Scaia
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorEthan W. Winckler
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorR. McAlister Council-Troche
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorCorresponding Author
Irving C. Allen
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorCorresponding Author
John B. Matson
Department of Chemistry, Virginia Tech Center for Drug Discovery, and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061 USA
Search for more papers by this authorAbstract
Persulfides (R−SSH) have been hypothesized as potent redox modulators and signaling compounds. Reported herein is the synthesis, characterization, and in vivo evaluation of a persulfide donor that releases N-acetyl cysteine persulfide (NAC-SSH) in response to the prokaryote-specific enzyme nitroreductase. The donor, termed NDP-NAC, decomposed in response to E. coli nitroreductase, resulting in release of NAC-SSH. NDP-NAC elicited gastroprotective effects in mice that were not observed in animals treated with control compounds incapable of persulfide release or in animals treated with Na2S. NDP-NAC induced these effects by the upregulation of beneficial small- and medium-chain fatty acids and through increasing growth of Turicibacter sanguinis, a beneficial gut bacterium. It also decreased the populations of Synergistales bacteria, opportunistic pathogens implicated in gastrointestinal infections. This study reveals the possibility of maintaining gut health or treating microbiome-related diseases by the targeted delivery of reactive sulfur species.
Conflict of interest
The authors declare no conflict of interest.
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