Characterizing the impact of podophyllotoxin on pulmonary toxicity and gut-lung microbiota interactions in SD rats based on TEC concept

作者：Min Wang, Xiao Ma, Junjie He, Jiaxing Sun, Feng Cai, Chuanxin Liu, Jiajia Duan · 发表于：Microbiology Spectrum · 年份：2025 · DOI：10.1128/spectrum.01653-24 · 被引用次数：8 · 研究领域：Plant-derived Lignans Synthesis and Bioactivity、Childhood Cancer Survivors' Quality of Life、Cannabis and Cannabinoid Research

ABSTRACT Podophyllotoxin (PPT), an extract from the traditional medicinal plant Dysosma , offers anti-viral and anti-cancer benefits, though its use is limited by toxicity. The mechanisms of PPT’s inherent pulmonary toxicity remain elusive. This study leverages the novel “Toxicological Evidence Chain” theory to explore the potential involvement of the “gut-lung axis” in PPT-induced pulmonary toxicity. In this study, we examined injury phenotypes in rats, evaluated pulmonary pathological changes, measured pro-inflammatory factors, and conducted comprehensive analyses of both pulmonary and gut microbiomes and metabolomics. Our findings indicate that exposure to PPT leads to significant pulmonary damage in these animals. The PPT group exhibited significantly elevated levels of total protein, albumin, alkaline phosphatase, and lactate dehydrogenase in bronchoalveolar lavage fluid, accompanied by marked upregulation of interleukin (IL)-18, tumor necrosis factor-alpha, IL-6, and IL-1β expression in lung tissue. Furthermore, 16S rRNA gene sequencing analysis revealed significant increases of Akkermansia , Escherichia - Shigella , and Bacteroides in both intestinal contents and lung tissue of PPT-treated animals, concomitant with notable elevations in short-chain fatty acids (SCFAs) such as isobutyric acid and isovaleric acid, and reductions in acetic acid, propionic acid, and butyric acid. The increased abundance of Akkermansia and Escherichia - Shigella may enhance pulmonary inflam...