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Updated: May 28, 2026

Applying Advanced In Vitro Culturing Technology to Study the Human Gut Microbiota
Published on: February 15, 2019
Activity-guided substructure prioritization accelerates discovery of gut microbiota-derived immune-regulating
Haoduo Zhao1, Liang Chi1, Zhenfa Zhang1
1Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA.
Researchers discovered new indole derivatives from gut microbes that activate the aryl hydrocarbon receptor (AhR), impacting host physiology. This work reveals novel microbiome-mediated reactions and their immune regulatory effects.
Area of Science:
- Microbiology
- Pharmacology
- Metabolomics
Background:
- Gut microbiota produce bioactive indole derivatives influencing host physiology.
- Indole derivatives often activate the aryl hydrocarbon receptor (AhR), suggesting structure-activity relationships (SAR).
Purpose of the Study:
- To develop a mass spectrometry pipeline for elucidating SAR in metabolite data.
- To identify unknown gut microbiome-derived indole derivatives with AhR agonistic potential.
Main Methods:
- Developed a substructure-activity relationship mass spectrometry pipeline.
- Applied the pipeline to identify novel gut microbial metabolites.
- Validated AhR agonistic activities and immune effects in male mice.
Main Results:
- Identified 22 metabolites with activity-related substructures, including four previously uncharacterized compounds.
- Discovered novel sulfonated and methylthiolated indole derivatives.
- Confirmed AhR agonistic activities and immune regulatory effects of the discovered compounds.
Conclusions:
- Presents a framework for MS data mining using activity-guided substructure prioritization.
- Enables discovery of bioactive microbiota-derived molecules.
- Highlights distinct microbiome-mediated reactions and their physiological relevance.
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