Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis

The Th17/Treg imbalance is an important cause of immune cell infiltration into the central nervous system (CNS) in multiple sclerosis (MS). The gut microbiota affects the Th17/Treg balance in the gut and in distal areas, such as the CNS, which further contributes to the onset and progression of MS....

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Main Authors: Jinyun Ma, Xiaojun Liu, Yan Zhao, Qijin Lu, Guiqing Ding, Yuanhua Wang, Xiaodong Cheng
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923024003058
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author Jinyun Ma
Xiaojun Liu
Yan Zhao
Qijin Lu
Guiqing Ding
Yuanhua Wang
Xiaodong Cheng
author_facet Jinyun Ma
Xiaojun Liu
Yan Zhao
Qijin Lu
Guiqing Ding
Yuanhua Wang
Xiaodong Cheng
author_sort Jinyun Ma
collection DOAJ
description The Th17/Treg imbalance is an important cause of immune cell infiltration into the central nervous system (CNS) in multiple sclerosis (MS). The gut microbiota affects the Th17/Treg balance in the gut and in distal areas, such as the CNS, which further contributes to the onset and progression of MS. Our previous studies have shown that Astragalus polysaccharide (APS) has a role in alleviating the clinical symptoms and demyelination of experimental autoimmune encephalomyelitis (EAE) mice, a classic MS model. However, the mechanism of action is not fully understood. In this study, we found that APS suppressed inflammation and regulated the Th17/Treg balance in the CNS and peripheral blood of EAE mice. It was further shown that APS inhibited gut inflammation and reduced Th17 function. The experiment with an antibiotic cocktail interfering with the gut microbiota proved that APS alleviated EAE by regulating the gut microbiota. Through 16S rRNA sequencing, we showed that APS regulated gut microbiota diversity and composition in EAE mice. Then, we found that APS regulated metabolite composition in feces and plasma, thus altering gut and blood metabolic functions. Metabolites related to this pathway, including sphingosine 1 phosphate (S1P), prostaglandin E2 (PGE2), ADP, and ATP, were downregulated by APS. The levels of bile acid metabolites such as taurochenodeoxycholate-7-sulfate and N-palmitoyl aspartic acid were upregulated by APS. In summary, our study demonstrated that APS exerts a suppressive effect on EAE by regulating gut microbiota composition, affecting metabolite composition, and improving the Th17/Treg balance in the peripheral blood and CNS.
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spelling doaj-art-af0c44791156452aa055324ff75963e52025-01-10T04:37:03ZengElsevierBrain Research Bulletin1873-27472025-01-01220111171Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axisJinyun Ma0Xiaojun Liu1Yan Zhao2Qijin Lu3Guiqing Ding4Yuanhua Wang5Xiaodong Cheng6Institute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaInstitute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaInstitute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaInstitute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaInstitute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaInstitute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaCorresponding author.; Institute of Clinical Immunology, Yue-yang Hospital of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, ChinaThe Th17/Treg imbalance is an important cause of immune cell infiltration into the central nervous system (CNS) in multiple sclerosis (MS). The gut microbiota affects the Th17/Treg balance in the gut and in distal areas, such as the CNS, which further contributes to the onset and progression of MS. Our previous studies have shown that Astragalus polysaccharide (APS) has a role in alleviating the clinical symptoms and demyelination of experimental autoimmune encephalomyelitis (EAE) mice, a classic MS model. However, the mechanism of action is not fully understood. In this study, we found that APS suppressed inflammation and regulated the Th17/Treg balance in the CNS and peripheral blood of EAE mice. It was further shown that APS inhibited gut inflammation and reduced Th17 function. The experiment with an antibiotic cocktail interfering with the gut microbiota proved that APS alleviated EAE by regulating the gut microbiota. Through 16S rRNA sequencing, we showed that APS regulated gut microbiota diversity and composition in EAE mice. Then, we found that APS regulated metabolite composition in feces and plasma, thus altering gut and blood metabolic functions. Metabolites related to this pathway, including sphingosine 1 phosphate (S1P), prostaglandin E2 (PGE2), ADP, and ATP, were downregulated by APS. The levels of bile acid metabolites such as taurochenodeoxycholate-7-sulfate and N-palmitoyl aspartic acid were upregulated by APS. In summary, our study demonstrated that APS exerts a suppressive effect on EAE by regulating gut microbiota composition, affecting metabolite composition, and improving the Th17/Treg balance in the peripheral blood and CNS.http://www.sciencedirect.com/science/article/pii/S0361923024003058Th17/Treg balanceMicrobiota-gut-brain axisNeuroinflammationAstragalus polysaccharideExperimental autoimmune encephalomyelitis (EAE)
spellingShingle Jinyun Ma
Xiaojun Liu
Yan Zhao
Qijin Lu
Guiqing Ding
Yuanhua Wang
Xiaodong Cheng
Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis
Brain Research Bulletin
Th17/Treg balance
Microbiota-gut-brain axis
Neuroinflammation
Astragalus polysaccharide
Experimental autoimmune encephalomyelitis (EAE)
title Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis
title_full Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis
title_fullStr Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis
title_full_unstemmed Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis
title_short Th17/Treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by Astragalus polysaccharides via the microbiota-gut-brain axis
title_sort th17 treg balance is regulated during the suppression of experimental autoimmune encephalomyelitis treated by astragalus polysaccharides via the microbiota gut brain axis
topic Th17/Treg balance
Microbiota-gut-brain axis
Neuroinflammation
Astragalus polysaccharide
Experimental autoimmune encephalomyelitis (EAE)
url http://www.sciencedirect.com/science/article/pii/S0361923024003058
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