Garlic-Derived Metabolites Exert Antioxidant Activity, Modulate Gut Microbiota Composition and Limit Citrobacter rodentium Infection in Mice

Ling Zhu, Audrey I.S. Andersen-Civil, Josue L. Castro-Meija, Dennis S. Nielsen, Alexandra Blanchard, John E. Olsen, Stig M. Thamsborg, Andrew R. Williams*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The garlic-derived compounds propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO) are metabolites with putative health benefits against intestinal inflammation that may be related to their antioxidant activity. However, the underlying mechanisms remain unclear, and whether PTS-PTSO can promote gut health by altering the microbiota and exert protection against enteric pathogens needs further investigation. Here, we explored the antioxidant activity of PTS-PTSO in murine macrophages in vitro, and in an in vivo model of bacterial infection with the bacterial pathogen Citrobacter rodentium. PTS-PTSO attenuated reactive oxygen species in lipopolysaccharide-stimulated macrophages in a nuclear factor erythroid factor 2-related factor 2 (Nrf2)-dependent manner, decreased nitric oxide levels both in macrophages in vitro and in the sera of mice fed PTS-PTSO, and had putatively beneficial effects on the commensal gut microbiota. Importantly, PTS-PTSO decreased faecal C. rodentium counts, concomitant with upregulation of Nrf2-related genes in colon tissue. Thus, PTS-PTSO mediates Nrf2-mediated antioxidant activity and modulates gut microbiota, which may protect the host against C. rodentium colonization. Our results provide further insight into how PTS-PTSO and related bioactive dietary compounds may reduce enteric infections.

Original languageEnglish
Article number2033
JournalAntioxidants
Volume11
Issue number10
Number of pages14
ISSN2076-3921
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • antioxidant activity
  • Citrobacter rodentium
  • nuclear factor erythroid factor 2-related factor 2
  • propyl propane thiosulfinate
  • propyl propane thiosulfonate

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