Aqueous Artemisia argyi extract mitigates acute lung injury in association with coordinated alterations in gut microbiota, metabolic homeostasis, and pulmonary inflammatory gene expression

Background: Artemisia argyi is a traditional medicinal herb with established anti-inflammatory and immunomodulatory properties. Its aqueous extract (AEAA), enriched in water-soluble bioactive constituents, exhibits favorable safety and bioavailability; however, its potential protective effects against acute lung injury (ALI) and its associations with systemic immunometabolic regulation remain incompletely understood. Methods: An LPS-induced ALI mouse model was established following 28 days of AEAA pretreatment. Lung histopathology, pulmonary edema, and inflammatory cytokines were evaluated. Integrated multi-omics analyses-including gut microbiota profiling, untargeted metabolomics of colonic contents and serum, and lung transcriptomics-were performed to characterize treatment-associated microbial, metabolic, and transcriptional alterations. Results: AEAA pretreatment dose-dependently alleviated lung injury, reduced pulmonary edema, and suppressed pro-inflammatory cytokines while restoring anti-inflammatory IL-10 levels. AEAA treatment was associated with partial reversal of LPS-induced gut dysbiosis, characterized by reduced abundance of inflammation-associated taxa and enrichment of beneficial genera, particularly Akkermansia and Lactobacillus. Metabolomic analyses revealed treatment-associated normalization of intestinal and systemic metabolic disturbances, including increased homeostasis-related metabolites and reduced inflammation-associated metabolites. Lung transcriptomic profiling suggested attenuation of LPS-associated transcriptional signatures related to NF-κB, MAPK, Toll-like receptor, and PI3K-AKT signaling pathways. Cross-omics integration further revealed coordinated associations among microbial shifts, metabolic remodeling, and pulmonary inflammatory gene expression. Conclusion: These findings suggest that aqueous Artemisia argyi extract is associated with mitigation of LPS-induced acute lung injury, accompanied by coordinated alterations in gut microbiota composition, host metabolic profiles, and pulmonary inflammatory gene expression. Although causal relationships were not established, this integrated multi-omics analysis provides a systems-level, hypothesis-generating framework supporting the potential of AEAA as a multi-target botanical candidate for ALI.