Work

Circadian tryptophan metabolism contributes to systemic aryl hydrocarbon receptor activity

Year: 2026

Type: article

Abstract: Diet-phytochemical derived activation, host and microbial tryptophan metabolism represent the dominant route to endogenously mediated stimulation of physiological Ah receptor (AHR) activity. Whether host tryptophan metabolism provides a phytochemical independent circadian AHR tone has not been established. Using mice maintained on a nocturnally restricted feeding schedule with a nutritionally defined diet, we utilized quantitative gene/protein expression analyses in conjunction with targeted metabolomics to examine the temporal relationship between host tryptophan metabolism and circadian AHR activity. Time-resolved, targeted LCMS metabolomic, gene, and protein expression analyses reveal circadian cycling of hepatic tryptophan metabolizing enzymes (TDO2, TAT, GOT1, GOT2, KAT1, KAT2, and IL4I1) and serum tryptophan metabolites (indole-3-acetate, indole-3-lactate, indole-3-propionate, indole aldehyde, kynurenine, kynurenic acid) previously established as AHR ligands. We observed cyclical hepatic AHR activity directed by circadian feeding. These data suggest that a circadian rhythm of tryptophan metabolism orchestrates a daily tone in AHR activity that likely modulates AHR dependent physiology.

Source: iScience

DOI: 10.1016/j.isci.2026.114680

Authors: Ethan W. Morgan, Iain A. Murray, Denise M. Coslo, Andrew D. Patterson, Gary H. Perdew

Institution: Pennsylvania State University

Language: English

Topic: Tryptophan and brain disorders

Subfield: Biological Psychiatry

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240