基础研究

二甲双胍保护 LPS 肺损伤:多组学指向肠源代谢特征

来源:Pharmaceuticals (Basel) · PMID 42943340 · DOI 10.3390/ph19101643** · 来源:IMA 知识库《文献层·文献监控卡片》2026-10-29 期 · 全文级(file_id dGBunAeRiRlm,下载实测 692,872 B) · 全文已获取并通过归属校验

数据日期 2026-10-29 · 生成时间 2026-10-29 06:03

研究问题

However, whether metformin attenuates LPS-induced pulmonary inflammation through coordinated remodeling of the gut microbiota and host-microbe metabolites remains insufficiently understood.

方法

Six-week-old SPF male C57BL/6J mice were obtained from GemPharmatech (Nanjing, China).;Mice were housed three per cage under specific pathogen-free conditions in a temperature-controlled room (21 ± 2 °C) with a 12 h light/dark cycle and free access to food and sterile drinking water.;Following a one-week acclimatization period, mice were randomly assigned to four groups: control (CON), LPS, metformin 200 mg/kg (MET 200 mg/kg), and metformin 400 mg/kg (MET 400 mg/kg).;Mice in the MET groups received metformin by oral gavage once daily for 7 days.

核心结论

These results identified a set of gut-serum synchronized metabolites associated with metformin-mediated improvement of lung inflammation, without establishing their colonic origin or causal role.;Histopathology and Immunostaining Lung and colon tissues were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H&E).;In the assessment of colonic-content samples, approximately 50 mg of sample was homogenized with 500 μL of 80% ice-cold methanol and incubated at –20 °C for 30 min. ‖ 结论:In conclusion, this study suggests that metformin alleviates LPS-induced pulmonary inflammation and colonic injury in association with coordinated remodeling of gut microbiota, intestinal luminal metabolites and circulating metabolites.

局限

The biological identity of several metformin-responsive metabolites provides plausible mechanistic clues for future studies.;The correlation networks were based on nominal p values and should be considered hypothesis-generating.;Future studies using metformin-only controls, post-LPS therapeutic dosing schedules, antibiotic depletion, fecal microbiota transplantation, germ-free animals, AMPK-pathway perturbation, isotope tracing, targeted metabolomics, and metabolite supplementation will be needed to test the causal structure and clinical translatability of this gut microbiota–metabolite–lung axis.

对本项目的价值

★★★★☆ 方法学进展决定我们能否在有限样本下检出真实效应,属基础设施级收益。命中核心 微生物组;设计 多组学。

全文来源

PMC JATS 全文(正文 37,534 字符,已过标题/DOI 逐字归属校验)

原文题录

  • 英文标题:Multi-Omics Analysis Identifies Gut-Associated Metabolic Signatures Associated with Metformin-Mediated Protection Against LPS-Induced Lung Injury.
  • 期刊与标识:Pharmaceuticals (Basel) · PMID 42943340 · DOI 10.3390/ph19101643**

B 级证据分级:B 级(同行评议临床前研究,主要为动物模型)

本文核心结论来自动物模型或体外细胞学,属临床前证据,不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义,与人类临床结局之间仍有距离。

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