Gut Microbiota-Derived Indole-3-Acetaldehyde Contributes to the Disease-Alleviating Effects of Kurarinone in Experimental Autoimmune Encephalomyelitis.
- 1Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
- 2Department of Neurology, Airforce Medical Center of PLA, Beijing, China.
Abstract
Multiple sclerosis (MS) is a central nervous system autoimmune disease primarily driven by Th1 and Th17 cells, whose onset and progression are closely associated with gut microbiota. Kurarinone (KU), an active component from Radix Sophora Flavescens, exhibits anti-inflammatory, immunoregulatory and gut microbiota-modulating properties. However, whether KU alleviates MS severity via a gut microbiota-mediated mechanism remains unclear. Here, we demonstrate that KU ameliorates experimental autoimmune encephalomyelitis (EAE)-an animal model of MS-by modulating the gut microbiota, particularly via enriching Akkermansia muciniphila, and A. muciniphila is essential for the protective effects of KU in EAE. Furthermore, KU elevates levels of the tryptophan metabolite indole-3-acetaldehyde (IAAld). IAAld levels are positively correlated with the relative abundance of A. muciniphila and negatively correlated with EAE severity. In vitro, A. muciniphila alone is sufficient to facilitate tryptophan metabolism to produce IAAld. IAAld treatment ameliorates EAE and reduces the frequencies of pathogenic Th1 and Th17 cells in mice. Mechanistically, IAAld activates the aryl hydrocarbon receptor (AhR) and suppresses JAK/STAT signaling, thereby dampening Th1 and Th17 differentiation; these effects are abolished following AhR blockade. Collectively, this study identifies a novel mechanism by which KU mitigates EAE via the gut metabolite IAAld-AhR-immune axis and unveils potential therapeutic targets for MS.
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BibTeX
@article{han2026microbiotaderived,
title = {{Gut Microbiota-Derived Indole-3-Acetaldehyde Contributes to the Disease-Alleviating Effects of Kurarinone in Experimental Autoimmune Encephalomyelitis.}},
author = {Xinyan Han and Jiaqi Ding and Zonghao Pan and Weitai He and Xue Kang and Cong Zhao and Yi Li and Di Wu and Hongzeng Li and Kaixi Ren and Jiaji Lin and Jun Guo},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78358},
url = {https://europepmc.org/article/MED/42885156},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut Microbiota-Derived Indole-3-Acetaldehyde Contributes to the Disease-Alleviating Effects of Kurarinone in Experimental Autoimmune Encephalomyelitis.
AU - Xinyan Han
AU - Jiaqi Ding
AU - Zonghao Pan
AU - Weitai He
AU - Xue Kang
AU - Cong Zhao
AU - Yi Li
AU - Di Wu
AU - Hongzeng Li
AU - Kaixi Ren
AU - Jiaji Lin
AU - Jun Guo
PY - 2026
DA - 2026/10/15
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78358
UR - https://europepmc.org/article/MED/42885156
AB - Multiple sclerosis (MS) is a central nervous system autoimmune disease primarily driven by Th1 and Th17 cells, whose onset and progression are closely associated with gut microbiota. Kurarinone (KU), an active component from Radix Sophora Flavescens, exhibits anti-inflammatory, immunoregulatory and gut microbiota-modulating properties. However, whether KU alleviates MS severity via a gut microbiota-mediated mechanism remains unclear. Here, we demonstrate that KU ameliorates experimental autoimmune encephalomyelitis (EAE)-an animal model of MS-by modulating the gut microbiota, particularly via enriching Akkermansia muciniphila, and A. muciniphila is essential for the protective effects of KU in EAE. Furthermore, KU elevates levels of the tryptophan metabolite indole-3-acetaldehyde (IAAld). IAAld levels are positively correlated with the relative abundance of A. muciniphila and negatively correlated with EAE severity. In vitro, A. muciniphila alone is sufficient to facilitate tryptophan metabolism to produce IAAld. IAAld treatment ameliorates EAE and reduces the frequencies of pathogenic Th1 and Th17 cells in mice. Mechanistically, IAAld activates the aryl hydrocarbon receptor (AhR) and suppresses JAK/STAT signaling, thereby dampening Th1 and Th17 differentiation; these effects are abolished following AhR blockade. Collectively, this study identifies a novel mechanism by which KU mitigates EAE via the gut metabolite IAAld-AhR-immune axis and unveils potential therapeutic targets for MS.
SN - 2198-3844
ER -