Multi-omics insights into Shenling Baizhu Powder's amelioration of murine asthma through gut microbiota and Glutamine-GLS1 pathway.

Abstract

Shenling Baizhu Powder (SLBZP) is a prominent formulation widely used in the treatment of pulmonary diseases. However, studies examining the mechanisms of SLBZP for treating asthma are limited. This study aimed to clarify the efficacy and possible mechanisms of SLBZP in the context of asthma from the perspective of gut microbiota-metabolism-immune crosstalk. Key parameters including airway hyperresponsiveness, lung pathological features and the expression of inflammatory mediators from Th2 and Th17 cells were employed to validate the anti-inflammatory properties of SLBZP. The anti-asthma mechanism of SLBZP was investigated using metagenomic sequencing, metabolomics, flow cytometry, RT-qPCR, immunohistochemistry (IHC) and immunofluorescence (IF). SLBZP demonstrated significant capacity to mitigate histopathological alterations associated with ovalbumin-induced asthma and suppress the secretion of inflammatory mediators (IL-4, IL-5, IL-13 and IL-17A) in BALF. Metagenomic results demonstrated that the protective effects of SLBZP were primarily associated with Ligilactobacillus, Eubacterium and Clostridium. Additionally, metabolomics results identified that three vital metabolic pathways were substantially regulated by SLBZP in asthmatic mice, especially D-glutamine and -glutamate metabolism. Furthermore, IHC and IF results showed that SLBZP significantly inhibited the expression of GLS1 and GOT1, which inhibited the conversion of L-glutamine to α-ketoglutarate and regulated the imbalance of Th1/Th2 and Treg/Th17. RT-qPCR results showed that SLBZP promoted the expressions of T-bet, IFN-γ, IL-10 and Foxp3 mRNA, and inhibited the expression of GATA3, IL-4, IL-5, IL-13, IL-17A and RORγt mRNA. The findings from flow cytometry provided additional evidence. Thus, this modulated the imbalance of Th1/Th2 and Treg/Th17 and exerted the immunomodulatory properties of SLBZP. SLBZP exerted protective effects against OVA-induced asthma and modified the structure and functional characteristics of the gut microbiota, and serum metabolite profiles in asthmatic mice. The anti-asthma mechanism of SLBZP may be associated with the modulation of the gut microbiota and Glutamine-GLS1 pathway.