腸内細菌が慢性疾患治療の鍵を握る可能性を示唆(Microbiome Breakthrough: Gut Bacterium May Hold Key to Future Treatments for Widespread Chronic Diseases)

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2025-08-01 コペンハーゲン大学(UCPH)

コペンハーゲン大学の研究チームは、腸内細菌が産生するタンパク質RORDEPが、血糖・食欲・脂肪代謝を制御するホルモン分泌を促進することを発見した。これにより体重減少、血糖値改善、骨密度上昇などが確認され、肥満、糖尿病、心血管疾患、骨粗鬆症などの治療に新たな道を開く可能性がある。すでに第1相臨床試験も開始されており、腸内細菌を用いた革新的な慢性疾患治療への応用が期待される。

<関連情報>

ヒト腸内における一般的な細菌によって合成されるポリペプチドがげっ歯類の代謝を改善する Polypeptides synthesized by common bacteria in the human gut improve rodent metabolism

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,… Oluf Pedersen
Nature Microbiology  Published:31 July 2025
DOI:https://doi.org/10.1038/s41564-025-02064-x

腸内細菌が慢性疾患治療の鍵を握る可能性を示唆(Microbiome Breakthrough: Gut Bacterium May Hold Key to Future Treatments for Widespread Chronic Diseases)

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.

医療・健康
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