Intestinal Lactobacillus murinus-derived small RNAs target porcine polyamine metabolism.

IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2024-10-08 Epub Date: 2024-10-03 DOI:10.1073/pnas.2413241121
Lijuan Fan, Bingnan Liu, Youxia Wang, Bin Tang, Tianqi Xu, Jian Fu, Chuanlong Wang, Yuan Liu, Liangpeng Ge, Hong Wei, Wenkai Ren
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Abstract

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 Lactobacillus murinus-derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, Lactobacillus murinus 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.

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肠道乳酸杆菌衍生的小核糖核酸靶向猪的多胺代谢。
肠道微生物群在宿主的新陈代谢中发挥着重要作用,但肠道微生物对多胺代谢的影响尚不清楚。在这里,我们发现无菌模型结肠中的多胺水平升高。从机理上讲,细胞外囊泡中的肠道乳酸杆菌衍生小核糖核酸通过靶向多胺代谢酶的表达来下调宿主的多胺代谢。此外,鼠乳杆菌还能通过降低小鼠体内的多胺水平,延缓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)小鼠和人类 CRC 标本的结肠中观察到小 RNA 丰度下降,同时多胺水平升高。总之,我们的研究确定了肠道微生物群调节宿主多胺代谢的一种特定基本机制,这为治疗多胺相关疾病提供了潜在的干预措施。
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来源期刊
CiteScore
19.00
自引率
0.90%
发文量
3575
审稿时长
2.5 months
期刊介绍: The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.
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