Polypeptides synthesized by common bacteria in the human gut improve rodent metabolism

IF 19.4 1区生物学 Q1 MICROBIOLOGY

Nature Microbiology Pub Date : 2025-07-31 DOI:10.1038/s41564-025-02064-x

Yong Fan, Liwei Lyu, Ruben Vazquez-Uribe, Wanliang Zhang, Mareike Bongers, Andreas Koulouktsis, Mengliu Yang, Vita Sereika-Bejder, Tulika Arora, Evelina Stankevic, Jeremy Armetta, Franziska Zosel, Charlotta D. de la Cour, Lotte Simonsen, Alina Kulakova, Michael Wierer, Pernille Harris, Joachim Gæde, Peter Rossing, Filip K. Knop, Tune H. Pers, Tue Haldor Hansen, Trine Nielsen, Ling Li, Kristian Strømgaard, Gangyi Yang, Morten Otto Alexander Sommer, Oluf Pedersen

{"title":"Polypeptides synthesized by common bacteria in the human gut improve rodent metabolism","authors":"Yong Fan, Liwei Lyu, Ruben Vazquez-Uribe, Wanliang Zhang, Mareike Bongers, Andreas Koulouktsis, Mengliu Yang, Vita Sereika-Bejder, Tulika Arora, Evelina Stankevic, Jeremy Armetta, Franziska Zosel, Charlotta D. de la Cour, Lotte Simonsen, Alina Kulakova, Michael Wierer, Pernille Harris, Joachim Gæde, Peter Rossing, Filip K. Knop, Tune H. Pers, Tue Haldor Hansen, Trine Nielsen, Ling Li, Kristian Strømgaard, Gangyi Yang, Morten Otto Alexander Sommer, Oluf Pedersen","doi":"10.1038/s41564-025-02064-x","DOIUrl":null,"url":null,"abstract":"<p>The human gut microbiota has the potential to synthesize proteins that may influence host metabolism. Here we report two polypeptides, RUMTOR-derived peptide (RORDEP) 1 and RORDEP2, circulating in human blood and synthesized by specific strains of gut commensal <i>Ruminococcus torques</i> that correlate inversely with adiposity in humans. Oral gavage with RORDEP-expressing strains improved glucose tolerance, increased bone density and reduced fat mass with an enhanced expression of genes and proteins involved in thermogenesis and lipolysis in lean mice on a high-fat diet and diet-induced obese mice. Recombinant RORDEP1 given to rats intraperitoneally decreased plasma gastric inhibitory polypeptide but increased glucagon-like peptide 1, peptide YY and insulin. Intestinal delivery of recombinant RORDEP1 to rats potentiated insulin-mediated inhibition of hepatic glucose production by downregulating genes and proteins controlling liver gluconeogenesis, glycogenolysis and lipogenesis but upregulating those involved in insulin signalling, glycogenesis and glycolysis. These preclinical findings warrant the exploration of RORDEPs for the prevention and treatment of human metabolic disorders.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"13 1","pages":""},"PeriodicalIF":19.4000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41564-025-02064-x","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The human gut microbiota has the potential to synthesize proteins that may influence host metabolism. Here we report two polypeptides, RUMTOR-derived peptide (RORDEP) 1 and RORDEP2, circulating in human blood and synthesized by specific strains of gut commensal Ruminococcus torques that correlate inversely with adiposity in humans. Oral gavage with RORDEP-expressing strains improved glucose tolerance, increased bone density and reduced fat mass with an enhanced expression of genes and proteins involved in thermogenesis and lipolysis in lean mice on a high-fat diet and diet-induced obese mice. Recombinant RORDEP1 given to rats intraperitoneally decreased plasma gastric inhibitory polypeptide but increased glucagon-like peptide 1, peptide YY and insulin. Intestinal delivery of recombinant RORDEP1 to rats potentiated insulin-mediated inhibition of hepatic glucose production by downregulating genes and proteins controlling liver gluconeogenesis, glycogenolysis and lipogenesis but upregulating those involved in insulin signalling, glycogenesis and glycolysis. These preclinical findings warrant the exploration of RORDEPs for the prevention and treatment of human metabolic disorders.

Abstract Image

查看原文本刊更多论文

人类肠道中常见细菌合成的多肽可改善啮齿动物的新陈代谢

人类肠道微生物群具有合成可能影响宿主代谢的蛋白质的潜力。在这里，我们报道了两种多肽，肿瘤衍生肽（RORDEP） 1和RORDEP2，它们在人类血液中循环，由肠道共生瘤胃球菌的特定菌株合成，与人类肥胖呈负相关。在高脂肪饮食的瘦小鼠和饮食诱导的肥胖小鼠中，用表达rordep的菌株灌胃可改善葡萄糖耐量，增加骨密度，减少脂肪量，并增强参与产热和脂肪分解的基因和蛋白质的表达。重组RORDEP1腹腔注射大鼠可使血浆胃抑制多肽降低，胰高血糖素样肽1、YY肽和胰岛素升高。重组RORDEP1通过下调控制肝脏糖异生、糖原分解和脂肪生成的基因和蛋白质，而上调参与胰岛素信号传导、糖原分解和糖酵解的基因和蛋白质，增强了胰岛素介导的肝糖生成抑制。这些临床前研究结果为探索RORDEPs预防和治疗人类代谢紊乱提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Microbiology Immunology and Microbiology-Microbiology

CiteScore

44.40

自引率

1.10%

发文量

226

期刊介绍： Nature Microbiology aims to cover a comprehensive range of topics related to microorganisms. This includes: Evolution: The journal is interested in exploring the evolutionary aspects of microorganisms. This may include research on their genetic diversity, adaptation, and speciation over time. Physiology and cell biology: Nature Microbiology seeks to understand the functions and characteristics of microorganisms at the cellular and physiological levels. This may involve studying their metabolism, growth patterns, and cellular processes. Interactions: The journal focuses on the interactions microorganisms have with each other, as well as their interactions with hosts or the environment. This encompasses investigations into microbial communities, symbiotic relationships, and microbial responses to different environments. Societal significance: Nature Microbiology recognizes the societal impact of microorganisms and welcomes studies that explore their practical applications. This may include research on microbial diseases, biotechnology, or environmental remediation. In summary, Nature Microbiology is interested in research related to the evolution, physiology and cell biology of microorganisms, their interactions, and their societal relevance.