A helminth-microbiota metabolic relay promotes disease tolerance.
6 affiliations
- 1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
- 2College of Food Science and Engineering, Jilin University, Changchun, China.
- 3Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians University of Würzburg, Würzburg, Germany.
- 4ANSES, Laboratory for Animal Health, Maisons-Alfort, France.
- 5UMR BIPAR, Anses, Laboratoire de Santé Animale, INRAE, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
- 6School of Life Sciences, Jilin University, Changchun, China.
Abstract
Persistent infection by helminths requires limiting inflammatory damage despite incomplete pathogen clearance, yet how helminths mobilize resident microbiota to establish this state remains unclear. Here we identify a cross-kingdom metabolic relay through which Trichinella spiralis promotes systemic disease tolerance. Infection selectively expanded Ligilactobacillus murinus and redirected microbial tryptophan metabolism toward indole-3-lactic acid (ILA), a direct ligand of the aryl hydrocarbon receptor (AhR). Antibiotic perturbation abrogated ILA production, AhR activation and Treg-Th17 remodeling, whereas transfer of helminth-conditioned fecal preparations or supplementation with L. murinus or ILA restored these responses. Pharmacological inhibition or genetic deletion of AhR eliminated the protection conferred by T. spiralis, L. murinus and ILA against endotoxin-induced lung injury. In lethal SARS-CoV-2 infection, oral ILA improved survival and limited pulmonary immunopathology without reducing viral burden, thereby uncoupling host protection from pathogen control. In a human COVID-19 cohort, ILA relative abundance remained inversely associated with IFN-γ after adjustment for available clinical covariates. These findings reveal that helminths can reprogram commensal metabolism to govern systemic immune tolerance and identify microbial ILA production as a tractable postbiotic strategy for limiting inflammatory tissue damage.
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BibTeX
@article{sun2026helminthmicrobiota,
title = {{A helminth-microbiota metabolic relay promotes disease tolerance.}},
author = {Ruohang Sun and Yi Liu and Yang Wang and Nuo Xu and Xiaoxiao Ma and Qingbo Lv and Xiufeng Zhao and Pascal Boireau and Zeming Wu and Mingyuan Liu and Xiaolei Liu and Xuemin Jin},
journal = {Gut microbes},
year = {2026},
month = oct,
doi = {10.1080/19490976.2026.2748132},
url = {https://europepmc.org/article/MED/42881529},
note = {CC BY},
}
RIS
TY - JOUR
TI - A helminth-microbiota metabolic relay promotes disease tolerance.
AU - Ruohang Sun
AU - Yi Liu
AU - Yang Wang
AU - Nuo Xu
AU - Xiaoxiao Ma
AU - Qingbo Lv
AU - Xiufeng Zhao
AU - Pascal Boireau
AU - Zeming Wu
AU - Mingyuan Liu
AU - Xiaolei Liu
AU - Xuemin Jin
PY - 2026
DA - 2026/10/15
JO - Gut microbes
DO - 10.1080/19490976.2026.2748132
UR - https://europepmc.org/article/MED/42881529
AB - Persistent infection by helminths requires limiting inflammatory damage despite incomplete pathogen clearance, yet how helminths mobilize resident microbiota to establish this state remains unclear. Here we identify a cross-kingdom metabolic relay through which Trichinella spiralis promotes systemic disease tolerance. Infection selectively expanded Ligilactobacillus murinus and redirected microbial tryptophan metabolism toward indole-3-lactic acid (ILA), a direct ligand of the aryl hydrocarbon receptor (AhR). Antibiotic perturbation abrogated ILA production, AhR activation and Treg-Th17 remodeling, whereas transfer of helminth-conditioned fecal preparations or supplementation with L. murinus or ILA restored these responses. Pharmacological inhibition or genetic deletion of AhR eliminated the protection conferred by T. spiralis, L. murinus and ILA against endotoxin-induced lung injury. In lethal SARS-CoV-2 infection, oral ILA improved survival and limited pulmonary immunopathology without reducing viral burden, thereby uncoupling host protection from pathogen control. In a human COVID-19 cohort, ILA relative abundance remained inversely associated with IFN-γ after adjustment for available clinical covariates. These findings reveal that helminths can reprogram commensal metabolism to govern systemic immune tolerance and identify microbial ILA production as a tractable postbiotic strategy for limiting inflammatory tissue damage.
SN - 1949-0976
SN - 1949-0984
ER -