肠道菌群失衡能够增加糖尿病风险
2016年7月21日，英国《自然》发表丹麦、瑞典、芬兰、德国、比利时、法国、瑞士、沙特阿拉伯、英国、中国（深圳华大基因、澳门科技大学、香港大学）的MetaHIT研究报告，发现特定的肠道细菌不平衡能够导致胰岛素抵抗，从而导致2型糖尿病等健康问题的风险增加。
该研究对277位非糖尿病丹麦人和75位2型糖尿病丹麦患者分析了胰岛素的作用，监测了血液中1200多种代谢物的浓度，并且对人肠道上百种细菌进行基于DNA的分析，以便探究肠道菌群的某些不平衡是否与常见的代谢疾病和心血管疾病存在因果关系。
结果发现，胰岛素作用能力下降因而产生胰岛素抵抗者，血液支链氨基酸（BCAA）水平增加。重要的是，血液BCAA水平上升与肠道菌群组成和功能发生的特定变化有相关性。
经过证实，肠道合成BCAA的主要驱动力是两种细菌：人体普氏菌和普通拟杆菌。为了在机制上测试肠道细菌是否导致胰岛素抵抗，该研究在3周内给小鼠喂食人体普氏菌。喂食人体普氏菌的小鼠与不喂食人体普氏菌的小鼠相比，血液BCAA水平增加，而且产生胰岛素抵抗和葡萄糖不耐受。
重要的是，该研究评估了不同细菌物种对疾病相关性的重要性，因此将一种特定细菌转移到小鼠体内时，能够使我们确定这种导致胰岛素抵抗的细菌。
Nature. 2016;535(7612):376-81.
Human gut microbes impact host serum metabolome and insulin sensitivity.
Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, Forslund K, Hildebrand F, Prifti E, Falony G, Le Chatelier E, Levenez F, Doré J, Mattila I, Plichta DR, Poho P, Hellgren LI, Arumugam M, Sunagawa S, Vieira-Silva S, Jorgensen T, Holm JB, Trost K; MetaHIT Consortium, Kristiansen K, Brix S, Raes J, Wang J, Hansen T, Bork P, Brunak S, Oresic M, Ehrlich SD, Pedersen O.
Collaborators (61): Almeida M, Antolin M, Artiguenave F, Batto JM, Bertalan M, Blottière H, Boruel N, Brechot C, Bruls T, Burgdorf K, Casellas F, Cultrone A, de Vos WM, Delorme C, Denariaz G, Derrien M, Dervyn R, Feng Q, Grarup N, Guarner F, Guedon E, Haimet F, Jamet A, Juncker A, Juste C, Kennedy S, Khaci G, Kleerebezem M, Knoll J, Layec S, Leclerc M, Leonard P, LePaslier D, M'Rini C, Maguin E, Manichanh C, Mende D, Mérieux A, Oozeer R, Parkhill J, Pelletier E, Pons N, Qin J, Rasmussen S, Renault P, Rescigno M, Sanchez N, Sicheritz-Ponten T, Tap J, Tims S, Torrejon A, Turner K, van de Guchte M, van Hylckama Vlieg JE, Vandemeulebrouck G, Varela E, Viega P, Weissenbach J, Winogradski Y, Yamada T, Zoetendal EG.
Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
PMID: 27409811
DOI: 10.1038/nature18646
