Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.
Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.
复制标题
妊娠糖尿病是由诊断前微生物群引起的炎症驱动的。
DOI：
10.1136/gutjnl-2022-328406
复制
发表时间：
2023-05
期刊：
影响因子：
24.5
通讯作者：
Koren, Omry
中科院分区：
文献类型：
--
作者：
Pinto, Yishay;Frishman, Sigal;Turjeman, Sondra;Eshel, Adi;Nuriel-Ohayon, Meital;Shrossel, Oshrit;Ziv, Oren;Walters, William;Parsonnet, Julie;Ley, Catherine;Johnson, Elizabeth L.;Kumar, Krithika;Schweitzer, Ron;Khatib, Soliman;Magzal, Faiga;Muller, Efrat;Tamir, Snait;Tenenbaum-Gavish, Kinneret;Rautava, Samuli;Salminen, Seppo;Isolauri, Erika;Yariv, Or;Peled, Yoav;Poran, Eran;Pardo, Joseph;Chen, Rony;Hod, Moshe;Borenstein, Elhanan;Ley, Ruth E.;Schwartz, Betty;Louzoun, Yoram;Hadar, Eran;Koren, Omry
妊娠期糖尿病（GDM）是一种没有糖尿病的妇女在怀孕期间被诊断为葡萄糖耐受不良的情况，通常在妊娠中期或晚期。早期诊断，以及在妊娠前三个月更好地了解其病理生理，可能有效降低发病率和相关的短期和长期发病率。我们全面分析了394名妊娠前三个月（GDM诊断前）妇女的肠道微生物组、代谢组、炎症细胞因子、营养和临床记录。然后，我们建立了一个模型，可以在典型诊断前几周预测GDM的发病。此外，我们通过三个独特队列的孕妇早期妊娠样本的粪便微生物群移植（FMT）证明了微生物组在疾病中的作用。我们发现，在后来发展为GDM的女性中，促炎细胞因子水平升高，粪便短链脂肪酸减少，微生物群改变。接下来，我们通过FMT实验证实，妊娠早期GDM相关微生物组成的差异在GDM诊断前10周以上导致炎症和胰岛素抵抗。根据这些观察结果，我们使用机器学习方法基于妊娠早期临床、微生物和炎症标志物来预测GDM，准确率很高。GDM的发病可以在妊娠的前三个月确诊，比目前公认的要早。此外，肠道微生物群似乎在炎症诱导的GDM发病机制中发挥作用，白细胞介素-6可能是发病机制的一个潜在因素。潜在的GDM标志物，包括微生物群，可以作为早期诊断和治疗干预的目标，从而导致预防。
Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.
登录
查看更多内容
影响因子：
5
作者：
COHEN, S;KAMARCK, T;MERMELSTEIN, R
通讯作者：
MERMELSTEIN, R
影响因子：
24.5
作者：
Cani PD
通讯作者：
Cani PD
影响因子：
9.8
作者：
Chorell, Elin;Hall, Ulrika Andersson;Holmang, Agneta
通讯作者：
Holmang, Agneta
影响因子：
3.3
作者：
Heimann E;Nyman M;Pålbrink AK;Lindkvist-Petersson K;Degerman E
通讯作者：
Degerman E
影响因子：
7.3
作者：
Gbotosho, Oluwabukola T.;Kapetanaki, Maria G.;Kato, Gregory J.
通讯作者：
Kato, Gregory J.