Fine mapping-based multi-omics analysis interprets the gut-lung axis function of SGLT2 inhibitors

作者：Fengqin Yuan, Tianlong Zhang, Sixiang Jia, Jianqiang Zhao, Binbin Wan, Gang Liu · 发表于：Frontiers in Cellular and Infection Microbiology · 年份：2024 · DOI：10.3389/fcimb.2024.1447327 · 被引用次数：7 · 研究领域：Gut microbiota and health、Drug Transport and Resistance Mechanisms、Helicobacter pylori-related gastroenterology studies

Background: Currently, Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrate additional effects beyond glucose control on the gut microbiota and circulating metabolites. The gut microbiota and metabolites have been found to be useful in elucidating potential biological mechanisms of pulmonary diseases. Therefore, our study aims to investigate the effects of gut microbiota and metabolites mediating SGLT2 inhibition in 10 pulmonary diseases through Mendelian randomization (MR) research. Methods: We conducted a two-sample, two-step MR study to assess the association between SGLT2 inhibition and 10 pulmonary diseases and to investigate the mediating effects of gut microbiota and metabolite. Gene-fine mapping and annotation of mediators by FUMA and Magma analyses were performed, and causal associations of mapped genes with diseases were assessed by muti-omics MR analyses. Possible side effects of SGLT2 inhibition were assessed by PheWAS analysis. Results: SGLT2 inhibition was linked to a reduced risk of T2DM, Interstitial lung disease (ILD), Pneumoconiosis, Pulmonary tuberculosis, and Asthma(OR=0.457, 0.054, 0.002, 0.280, 0.706). The family Enterobacteriaceae and order Enterobacteriales were associated with SGLT2 inhibition and ILD(95% CI:0.079-0.138). The family Alcaligenaceae and X-12719 were linked to pneumoconiosis (95% CI: 0.042-0.120, 0.050-0.099). The genus Phascolarctobacterium was connected to pulmonary tuberculosis (95% CI: 0.236-0.703).The degree of unsaturation...