Gut bacterial lauroyl tryptamine reduces GPR183-associated inflammatory responses in human macrophages and T cells in vitro
- 1Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands.
- 2Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, Academic Medical Center (AMC), Amsterdam, Netherlands.
- 3Department of Chemistry, University of Zurich, Zurich, Switzerland.
Abstract
Introduction: Recent research has highlighted the role of gut microbiota in producing bioactive metabolites that interact with G-protein coupled receptors (GPRs) and influence immune responses. Lauroyl tryptamine (LT), a metabolite produced by Agathobacter rectalis (formerly Eubacterium rectale ), has been reported to antagonize GPR183, a receptor implicated in inflammatory bowel diseases (IBD). LT inhibits the binding of GPR183 with its natural ligands 7a,25-dihydroxycholesterol (OHC).
Methods: Here, we analyzed the GPR183 gene expression in intestinal tissues from IBD patients and non-IBD controls, as well as our previous single-cell transcriptomic dataset to identify key GPR183-expressing cells. We then use in vitro THP-1 derived macrophage and Jurkat T cell culture to test the effects of LT on inflammatory responses.
Results and discussion: The GPR183 gene expression is elevated specifically in colonic and rectal tissues of ulcerative colitis patients, but not in Crohn’s disease or ileal tissue. By analyzing single-cell transcriptomic dataset, we identified monocytes/macrophages, T cells, B cells, and innate lymphoid cells as key GPR183 -expressing populations in human intestine. Using cell culture models, we demonstrated that LT modulates inflammatory pathways. In LPS-stimulated macrophages, OHC increased transcription of pro-inflammatory genes IL6, TNFA , and IL1B , which are reduced by LT. In activated Jurkat T cells, LT slightly decreased the OHC-mediated increase in the transcription of IL2. These findings support the hypothesis that LT, a known GPR183 antagonist, could modulate GPR183-associated inflammation in human macrophages and T cells in a context- and cell type-dependent manner, offering potential mechanistic insights into bioactive metabolite-mediated host-microbiota interactions in human intestine.
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BibTeX
@article{lezzerini2026bacterial,
title = {{Gut bacterial lauroyl tryptamine reduces GPR183-associated inflammatory responses in human macrophages and T cells in vitro}},
author = {Marco Lezzerini and Vera Spek and Ivan C N Fung and Michelle Jessy Müller and Aleksej Kubelka and Simon Sieber and Wouter J de Jonge and Andrew Y F Li Yim and Anje A Te Velde and Jianbo Zhang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1878373},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1878373/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Gut bacterial lauroyl tryptamine reduces GPR183-associated inflammatory responses in human macrophages and T cells in vitro
AU - Marco Lezzerini
AU - Vera Spek
AU - Ivan C N Fung
AU - Michelle Jessy Müller
AU - Aleksej Kubelka
AU - Simon Sieber
AU - Wouter J de Jonge
AU - Andrew Y F Li Yim
AU - Anje A Te Velde
AU - Jianbo Zhang
PY - 2026
DA - 2026/10/15
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1878373
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1878373/full
AB - Introduction: Recent research has highlighted the role of gut microbiota in producing bioactive metabolites that interact with G-protein coupled receptors (GPRs) and influence immune responses. Lauroyl tryptamine (LT), a metabolite produced by Agathobacter rectalis (formerly Eubacterium rectale ), has been reported to antagonize GPR183, a receptor implicated in inflammatory bowel diseases (IBD). LT inhibits the binding of GPR183 with its natural ligands 7a,25-dihydroxycholesterol (OHC). Methods: Here, we analyzed the GPR183 gene expression in intestinal tissues from IBD patients and non-IBD controls, as well as our previous single-cell transcriptomic dataset to identify key GPR183-expressing cells. We then use in vitro THP-1 derived macrophage and Jurkat T cell culture to test the effects of LT on inflammatory responses. Results and discussion: The GPR183 gene expression is elevated specifically in colonic and rectal tissues of ulcerative colitis patients, but not in Crohn’s disease or ileal tissue. By analyzing single-cell transcriptomic dataset, we identified monocytes/macrophages, T cells, B cells, and innate lymphoid cells as key GPR183 -expressing populations in human intestine. Using cell culture models, we demonstrated that LT modulates inflammatory pathways. In LPS-stimulated macrophages, OHC increased transcription of pro-inflammatory genes IL6, TNFA , and IL1B , which are reduced by LT. In activated Jurkat T cells, LT slightly decreased the OHC-mediated increase in the transcription of IL2. These findings support the hypothesis that LT, a known GPR183 antagonist, could modulate GPR183-associated inflammation in human macrophages and T cells in a context- and cell type-dependent manner, offering potential mechanistic insights into bioactive metabolite-mediated host-microbiota interactions in human intestine.
SN - 1664-3224
ER -