Presentation Type

Poster Presentation

Abstract

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease primarily affecting premature infants. Toll-like receptor 4 (TLR4)-mediated epithelial damage allows microbial translocation, triggering inflammation that can lead to sepsis and death. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor, and AhR ligands have been shown to prevent NEC in a mouse model. Indole, an AhR ligand, has been reported to extend the healthspan of C. elegans, and we have shown previously it mitigates poor outcomes in wild-type worms infected with Cronobacter sakazakii (Cs), a bacterial pathogen linked to NEC. We hypothesized that C. elegans must express ahr-1, the ortholog of human AHR, for indole to confer protection against Cs infection. To test this, we used ZG24 C. elegans, an ahr-1 knockout strain, and performed a larval stage 4 (L4) killing assay. Worms were infected with Cs on day 0 and treated with either indole or methanol (vehicle control) on days 1 and 4. We monitored motility over seven days and conducted a heat stress assay on day 7 to assess health. Our results showed no difference in health outcomes between Cs-infected worms treated with indole versus methanol, indicating that indole-mediated protection requires AhR activity. These findings highlight AhR ligands as potential therapeutic candidates for NEC and support further investigation into their protective mechanisms.

Faculty Mentor

Dr. Kyle Brawner

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Indole improves outcomes of Cronobacter sakazakii infection in C. elegans through ahr-1

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease primarily affecting premature infants. Toll-like receptor 4 (TLR4)-mediated epithelial damage allows microbial translocation, triggering inflammation that can lead to sepsis and death. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor, and AhR ligands have been shown to prevent NEC in a mouse model. Indole, an AhR ligand, has been reported to extend the healthspan of C. elegans, and we have shown previously it mitigates poor outcomes in wild-type worms infected with Cronobacter sakazakii (Cs), a bacterial pathogen linked to NEC. We hypothesized that C. elegans must express ahr-1, the ortholog of human AHR, for indole to confer protection against Cs infection. To test this, we used ZG24 C. elegans, an ahr-1 knockout strain, and performed a larval stage 4 (L4) killing assay. Worms were infected with Cs on day 0 and treated with either indole or methanol (vehicle control) on days 1 and 4. We monitored motility over seven days and conducted a heat stress assay on day 7 to assess health. Our results showed no difference in health outcomes between Cs-infected worms treated with indole versus methanol, indicating that indole-mediated protection requires AhR activity. These findings highlight AhR ligands as potential therapeutic candidates for NEC and support further investigation into their protective mechanisms.

 

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