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Targeted Delivery of Persulfides to the Gut: Effects on the Microbiome
Author(s) -
Dillon Kearsley M.,
Morrison Holly A.,
Powell Chadwick R.,
Carrazzone Ryan J.,
RingelScaia Veronica M.,
Winckler Ethan W.,
CouncilTroche R. McAlister,
Allen Irving C.,
Matson John B.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202014052
Subject(s) - nitroreductase , bacteria , chemistry , microbiology and biotechnology , microbiome , cysteine , downregulation and upregulation , in vivo , enzyme , biochemistry , biology , gene , genetics
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 Na 2 S. 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.