Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
L-Kynurenine Reshapes Immune Microenvironment to Alleviate Methamphetamine-Induced Chronic Lung Injury Through Gut-Lung Axis
24 Pages Posted: 27 Jan 2025
More...Abstract
Long-term methamphetamine (MA) abuse is strongly associated with severe lung injury. The gut microbiota and its metabolites are crucial in the gut-lung axis. Microbiome metabolites are one way to understand the interactions between microbes and disease. However, microbial mechanism of MA-induced pulmonary injury remains unclear. This work aims to identify an omics characteristic factor and investigate its action mechanism by 16s rDNA sequencing, LC-MS/MS non-targeted metabolomics analysis, hemodynamics, flow cytometry, Western blotting, and other cellular molecular biology and morphological techniques. Through the combined analysis of gut microbiome and metabolite omics, MA was observed to affect the structure of the gut microbiota and drive the reprogramming of metabolites, resulting in a reduction of Lactobacillus and metabolite l-kynurenine (L-KYN). Consequently, L-KYN, the end product of Lactobacillus, was strongly associated with MA-induced lung injury. L-KYN induced differentiation of Treg cells from CD4+ T cells and reshaped the immune microenvironment. L-KYN induced the secretion of IL-10 from Treg cells and mediated the communication between Treg cells and alveolar epithelial cells (AEC) via IL-10. L-KYN alleviated lung inflammation and damages of the alveolar barrier induced by MA through IL-10/JAK1/STAT3 pathway. The above mechanism was further confirmed in vivo. Therefore, it was indicated from the perspective of gut microbiota-metabolite-immune network regulation that an omics feature factor L-kynurenine reshaped immune microenvironment to alleviate methamphetamine-induced chronic lung injury through gut-lung axis. It provides a novel theoretical and experimental basis for the prevention and treatment of MA-induced lung injury.
Keywords: L-kynurenine, Methamphetamine, Chronic lung injury, Gut microbiota, Microbiome, Metabolomics, Gut-lung axis, Treg, immune microenvironment, IL-10
Suggested Citation: Suggested Citation