State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
National Center of Technology Innovation for Pigs, Chongqing 402460, China.
Proc Natl Acad Sci U S A. 2024 Oct 8;121(41):e2413241121. doi: 10.1073/pnas.2413241121. Epub 2024 Oct 3.
Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal -derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, delays recovery of dextran sodium sulfate-induced colitis by reducing polyamine levels in mice. Notably, a decline in the abundance of small RNAs was observed in the colon of mice with colorectal cancer (CRC) and human CRC specimens, accompanied by elevated polyamine levels. Collectively, our study identifies a specific underlying mechanism used by intestinal microbiota to modulate host polyamine metabolism, which provides potential intervention for the treatment of polyamine-associated diseases.
肠道微生物群在宿主代谢中起着至关重要的作用;然而,肠道微生物对多胺代谢的影响尚不清楚。在这里,我们发现无菌模型在结肠中具有更高的多胺水平。从机制上讲,来源于肠道的细胞外囊泡中的小 RNA 通过靶向多胺代谢中酶的表达来下调宿主多胺代谢。此外, 通过降低小鼠多胺水平来延迟葡聚糖硫酸钠诱导的结肠炎的恢复。值得注意的是,在结直肠癌(CRC)小鼠和人 CRC 标本的结肠中观察到小 RNA 的丰度下降,同时多胺水平升高。总的来说,我们的研究确定了肠道微生物群用于调节宿主多胺代谢的特定潜在机制,这为多胺相关疾病的治疗提供了潜在的干预措施。