Sheng-Jiang Powder and Akkermansia muciniphila interventions in experimental autoimmune encephalomyelitis: microbiota-linked sphingolipid/S1PR1-associated barrier remodeling
Abstract
BackgroundSheng-Jiang Powder (SJP) is a classical traditional Chinese medicine formula with reported anti-inflammatory and gut microbiota-modulating activities. However, whether its protective effects in experimental autoimmune encephalomyelitis (EAE) are associated with gut microbial changes, sphingolipid/S1P metabolism, and S1PR1-related barrier signaling remains unclear.MethodsEAE was induced in female C57BL/6 mice, with SJP, Akkermansia muciniphila (AKK intervention group), or their combination administered from day 2 after immunization, before the expected onset of clinical signs. Clinical severity, histopathology, inflammatory cytokines, and barrier-related markers were evaluated. Gut microbiota changes were assessed by fluorescence in situ hybridization and 16S rRNA sequencing. Untargeted serum and fecal metabolomic profiles were analyzed by LC–MS. Serum-detected SJP-related compounds were characterized by UPLC–MS/MS and analyzed using network pharmacology. S1PR1-associated signaling was further examined by Western blotting, immunofluorescence, and S1PR1-overexpression experiments in bEnd.3 cells.ResultsPre-onset SJP, AKK, and AKK_SJP interventions reduced EAE severity, inflammatory pathology, and serum inflammatory cytokine levels. These effects were accompanied by improved colonic barrier markers, increased Akkermansia-associated mucosal signals, and altered gut microbial profiles. Serum and fecal metabolomic analyses highlighted lipid-related pathways, particularly sphingolipid metabolism and signaling. Serum-detected SJP-related compounds mapped to a candidate network containing S1PR1. In colon and CNS tissues, treatment altered barrier-related markers and S1PR1 expression. In bEnd.3 cells, S1PR1 overexpression reduced ZO-1 expression, whereas SJP-containing serum partially attenuated this change.ConclusionsPre-onset SJP administration alleviated EAE and was accompanied by changes in gut microbial composition, sphingolipid/S1P-related metabolism, S1PR1 expression, and barrier-related markers. AKK-related intervention showed overlapping effects on several microbial, metabolic, and barrier-associated markers.
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BibTeX
@article{xia2026shengjiang,
title = {{Sheng-Jiang Powder and Akkermansia muciniphila interventions in experimental autoimmune encephalomyelitis: microbiota-linked sphingolipid/S1PR1-associated barrier remodeling}},
author = {Hui Xia and Jingjing Zeng and Ye Tang and Tianshan Liang and Lilin Peng and Chang Zhou and Yibo Zhan and Guixian Chen and Min Zhao and Haoyou Xu and Longlong Wen and Jiahui Zhang and Wenlin Yu and Zequan Zheng and Yuanqi Zhao},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1933272},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1933272},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sheng-Jiang Powder and Akkermansia muciniphila interventions in experimental autoimmune encephalomyelitis: microbiota-linked sphingolipid/S1PR1-associated barrier remodeling
AU - Hui Xia
AU - Jingjing Zeng
AU - Ye Tang
AU - Tianshan Liang
AU - Lilin Peng
AU - Chang Zhou
AU - Yibo Zhan
AU - Guixian Chen
AU - Min Zhao
AU - Haoyou Xu
AU - Longlong Wen
AU - Jiahui Zhang
AU - Wenlin Yu
AU - Zequan Zheng
AU - Yuanqi Zhao
PY - 2026
DA - 2026/11/06
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1933272
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1933272
AB - BackgroundSheng-Jiang Powder (SJP) is a classical traditional Chinese medicine formula with reported anti-inflammatory and gut microbiota-modulating activities. However, whether its protective effects in experimental autoimmune encephalomyelitis (EAE) are associated with gut microbial changes, sphingolipid/S1P metabolism, and S1PR1-related barrier signaling remains unclear.MethodsEAE was induced in female C57BL/6 mice, with SJP, Akkermansia muciniphila (AKK intervention group), or their combination administered from day 2 after immunization, before the expected onset of clinical signs. Clinical severity, histopathology, inflammatory cytokines, and barrier-related markers were evaluated. Gut microbiota changes were assessed by fluorescence in situ hybridization and 16S rRNA sequencing. Untargeted serum and fecal metabolomic profiles were analyzed by LC–MS. Serum-detected SJP-related compounds were characterized by UPLC–MS/MS and analyzed using network pharmacology. S1PR1-associated signaling was further examined by Western blotting, immunofluorescence, and S1PR1-overexpression experiments in bEnd.3 cells.ResultsPre-onset SJP, AKK, and AKK_SJP interventions reduced EAE severity, inflammatory pathology, and serum inflammatory cytokine levels. These effects were accompanied by improved colonic barrier markers, increased Akkermansia-associated mucosal signals, and altered gut microbial profiles. Serum and fecal metabolomic analyses highlighted lipid-related pathways, particularly sphingolipid metabolism and signaling. Serum-detected SJP-related compounds mapped to a candidate network containing S1PR1. In colon and CNS tissues, treatment altered barrier-related markers and S1PR1 expression. In bEnd.3 cells, S1PR1 overexpression reduced ZO-1 expression, whereas SJP-containing serum partially attenuated this change.ConclusionsPre-onset SJP administration alleviated EAE and was accompanied by changes in gut microbial composition, sphingolipid/S1P-related metabolism, S1PR1 expression, and barrier-related markers. AKK-related intervention showed overlapping effects on several microbial, metabolic, and barrier-associated markers.
SN - 1664-3224
ER -