Jianpi Yiqi Busui Formula (JPYQBSF) alleviates immune microenvironment disorder of myasthenia gravis by targeting PD-1 expression of Treg through LDHA/ gut microbiota-mediated lactate metabolism and histone lactylation

ABSTRACT: autoantibodies impairing neuromuscular junction function. Jianpi Yiqi Busui Formula (JPYQBSF) is a traditional Chinese herbal compound with multiple bioactive constituents, but its effects in MG remain unclear. Purpose: This study investigated the therapeutic effects and mechanisms of JPYQBSF in MG, focusing on immune homeostasis, gut microbiota, lactate metabolism, and Treg function via histone lactylation. Study design: A combined clinical and preclinical study was conducted, integrating anti-acetylcholine receptor antibody-positive MG patients, experimental autoimmune MG (EAMG) rats, and multi-omics mechanistic analyses. Methods: MG patients received JPYQBSF for six months, with clinical and immunological assessments. In EAMG rats, behavioral tests, electrophysiology, flow cytometry, 16S rRNA sequencing, metabolomics, proteomics, and histone modification assays were performed. LDHA inhibition and network pharmacology were used to clarify mechanisms. Results: JPYQBSF improved neuromuscular symptoms and restored Treg/Th17 balance (p<0.01). Multi-omics analyses revealed regulation of LDHA-mediated lactate metabolism and gut microbiota. In Tregs, JPYQBSF increased PD-1 expression and H3K18 lactylation, effects abolished by LDHA inhibition (p<0.001). LDHA inhibition exacerbated inflammation and disrupted Treg/Th17 balance in EAMG rats, whereas JPYQBSF mitigated these effects. Conclusion: JPYQBSF rebalanced immune microenvironment disorder in MG via LDHA/gut microbiota-mediated lactate metabolism and histone lactylation–dependent PD-1 activation in Tregs. These findings support its potential clinical application in MG.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Yibin Zhang  

PROVIDER: PXD078341 | iProX | Thu May 14 00:00:00 BST 2026

REPOSITORIES: iProX