Gut microbiota-dependent metabolism of 6-shogaol generates bioactive metabolites that mediate its anti-inflammatory

Shuwei Zhang1, Yantao Zhao1, Rachel C Newsome2

  • 1Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Agricultural and Technical State University, North Carolina Research Campus, Kannapolis, NC, USA. ssang@ncat.edu.

Food & Function
|June 23, 2026
PubMed

Insights

Gut bacteria extensively metabolize 6-shogaol (6S), a ginger compound. Microbial metabolites of 6S retain significant anti-inflammatory properties, impacting key inflammatory pathways.

Area of Science:

  • Pharmacology
  • Microbiology
  • Natural Products

Background:

  • 6-Shogaol (6S), a key ginger compound, has known anti-inflammatory effects.
  • The role of gut microbiota in 6S metabolism and its biological impact is not well understood.

Purpose of the Study:

  • To investigate the role of gut microbiota in the metabolism of 6S.
  • To identify and characterize bioactive microbial metabolites of 6S.
  • To evaluate the anti-inflammatory potential of 6S microbial metabolites.

Main Methods:

  • Comparison of 6S metabolism in germ-free (GF) and specific pathogen-free (SPF) mice.
  • Isolation and structural elucidation of novel metabolites using LC-MS/MS and NMR.
  • Chemical synthesis for metabolite confirmation.
  • In vitro assays on RAW 264.7 macrophages to assess anti-inflammatory effects (NO, iNOS, COX-2, NF-κB).
  • In vivo studies evaluating inflammatory markers (TNF-α, IL-6) after LPS challenge.

Main Results:

  • Gut microbiota significantly influences 6S metabolism in vivo.
  • Two new microbial metabolites of 6S were identified and synthesized.
  • A potent fecal fraction containing 6S metabolites suppressed inflammatory mediators in macrophages.
  • Microbial metabolites of 6S attenuated LPS-induced inflammation in mice, comparable to 6S itself.

Conclusions:

  • Gut microbiota extensively metabolizes 6S.
  • Microbial metabolites of 6S possess significant anti-inflammatory activity.
  • These findings highlight the importance of microbial biotransformation in the bioactivity of natural compounds.

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