Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae.
Angiogenin maintains gut microbe homeostasis by balancing α-Proteobacteria and Lachnospiraceae.
复制标题
血管生成素通过平衡 α-变形菌和 Lachnospiraceae 来维持肠道微生物稳态
作者：
Sun D;Bai R;Zhou W;Yao Z;Liu Y;Tang S;Ge X;Luo L;Luo C;Hu GF;Sheng J;Xu Z
抗菌肽在维持肠道健康方面发挥着重要作用，并与IBD有关。本研究旨在探讨肠源性AMP--血管生成素(Ang)对肠道微生物区系的影响及其与IBD的关系。在不同的共栖结肠炎模型和粪便微生物区系移植模型中，评价血管紧张素转换酶对微生物区系的影响及其在结肠炎中的作用。通过16S rDNA测序确定Ang调节细菌，并通过细菌定植分析它们在结肠炎中的作用。采用微生物学和生物化学方法进一步研究了Ang的种属特异性抗菌活性及其作用机制。对IBD粪便标本进行ANG水平和主要致病菌的特征分析。Ang调节微生物区系组成，抑制肠道炎症。具体地说，小鼠的血管紧张素1缺乏导致保护肠道共生的乳杆菌科细菌减少，但增加了α-变形杆菌的共生菌株。血管紧张素与α-变形杆菌的直接结合导致细菌膜完整性的致死性破坏，从而促进乳酸菌的生长，而α-变形杆菌则对此有拮抗作用。口服Ang1逆转了Ang1基因缺陷小鼠的菌群失调，减轻了结肠炎的严重程度。建立ANG、细菌鉴定与IBD患者病情的相关性。这些发现证明了Ang在塑造肠道微生物组成从而维持肠道健康方面的新作用，表明Ang-微生物区轴可能被开发为一种潜在的预防和/或治疗与失调相关的肠道疾病的方法。
Antimicrobial peptides (AMPs) play essential roles in maintaining gut health and are associated with IBD. This study is to elucidate the effect of angiogenin (ANG), an intestine-secreted AMP, on gut microbiota and its relevance with IBD. The effect of ANG on microbiota and its contribution to colitis were evaluated in different colitis models with co-housing and faecal microbiota transplantation. ANG-regulated bacteria were determined by 16S rDNA sequencing and their functions in colitis were analysed by bacterial colonisation. The species-specific antimicrobial activity of ANG and its underlying mechanism were further investigated with microbiological and biochemical methods. ANG level and the key bacteria were characterised in IBD faecal samples. ANG regulated microbiota composition and inhibited intestinal inflammation. Specifically, Ang1 deficiency in mice led to a decrease in the protective gut commensal strains of Lachnospiraceae but an increase in the colitogenic strains of α-Proteobacteria. Direct binding of ANG to α-Proteobacteria resulted in lethal disruption of bacterial membrane integrity, and consequently promoted the growth of Lachnospiraceae, which otherwise was antagonised by α-Proteobacteria. Oral administration of ANG1 reversed the dysbiosis and attenuated the severity of colitis in Ang1-deficient mice. The correlation among ANG, the identified bacteria and IBD status was established in patients. These findings demonstrate a novel role of ANG in shaping gut microbe composition and thus maintaining gut health, suggesting that the ANG-microbiota axis could be developed as a potential preventive and/or therapeutic approach for dysbiosis-related gut diseases.
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影响因子：
3.7
作者：
Berkowitz, Loni;Pardo-Roa, Catalina;Bueno, Susan M.
通讯作者：
Bueno, Susan M.
DOI：
10.1007/s00018-017-2693-8
发表时间：
2018-01
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Hugenholtz F;de Vos WM
通讯作者：
de Vos WM
影响因子：
2.9
作者：
FETT, JW;STRYDOM, DJ;VALLEE, BL
通讯作者：
VALLEE, BL
影响因子：
4.4
作者：
Cho, S;Beintema, JJ;Zhang, JZ
通讯作者：
Zhang, JZ
影响因子：
56.9
作者：
Coyte, Katharine Z.;Schluter, Jonas;Foster, Kevin R.
通讯作者：
Foster, Kevin R.