IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans.
IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans.
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DOI：
10.1007/s00125-022-05711-8
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发表时间：
2022-08
期刊：
影响因子：
8.2
通讯作者：
Wen, Li
中科院分区：
文献类型：
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作者：
Pearson, James A.;Ding, Heyuan;Hu, Changyun;Peng, Jian;Galuppo, Brittany;Wong, F. Susan;Caprio, Sonia;Santoro, Nicola;Wen, Li
IgM是由B细胞产生的第一抗体，我们假设肠道微生物群的IgM抗体可能在肥胖和2型糖尿病的免疫代谢中发挥作用。为了验证我们的假设，我们使用了缺乏激活诱导的胞苷脱氨酶（Aid-/-[也称为Aicda-/-]）的B6小鼠，它们只分泌IgM抗体，以及人类粪便样本。我们研究了与野生型小鼠相比，Aid−/− B6小鼠在高脂饮食诱导的肥胖（HFDIO）中的免疫代谢效应和肠道微生物变化。为了确定小鼠和人类之间的相似性，从患有正常葡萄糖耐量（NGT）的肥胖儿童和青少年，患有葡萄糖耐受不良（IGT）的肥胖儿童和青少年，或新诊断为2型糖尿病的肥胖儿童和青少年中收集人类粪便样本，用于将粪便微生物群移植（FMT）到无菌（GF）B6小鼠中，并评估IgM结合的细菌和免疫反应。与野生型小鼠相比，Aid−/− B6小鼠由于IgM水平丰富而加重了HFDIO。与使用野生型小鼠粪便微生物群的FMT相比，从Aid−/− B6小鼠到GF B6小鼠的FMT促进了受体小鼠的体重增加。患有2型糖尿病的肥胖青年有更多的IgM结合的肠道细菌。使用来自患有2型糖尿病的肥胖青年的粪便用于FMT到GF B6小鼠，我们观察到肠道微生物群促进了受体GF B6小鼠的体重增加和葡萄糖耐量受损。重要的是，这些肥胖年轻个体的一些临床特征在FMT后的GF B6小鼠中得到反映。我们的研究结果表明，IgM结合的肠道微生物群可能在肥胖和2型糖尿病的免疫发病机制中发挥重要作用，并提供了小鼠和人类肥胖和2型糖尿病中IgM之间的新联系。支持当前研究的16 s rRNA测序数据集已保存在NCBI SRA公共存储库（https：//www.ncbi.nlm.nih.gov/sra;登录号SAMN 18796639）。在线版本包含同行评审但未经编辑的补充材料，可通过10.1007/s 00125 -022-05711-8获得。
IgM is the primary antibody produced by B cells and we hypothesise that IgM antibodies to gut microbiota may play a role in immunometabolism in obesity and type 2 diabetes. To test our hypothesis, we used B6 mice deficient in activation-induced cytidine deaminase (Aid−/− [also known as Aicda−/−]) which secrete only IgM antibodies, and human faecal samples. We studied the immunometabolic effects and gut microbial changes in high-fat-diet-induced obesity (HFDIO) in Aid−/− B6 mice compared with wild-type mice. To determine similarities between mice and humans, human stool samples were collected from children and adolescents who were obese with normal glucose tolerance (NGT), obese with glucose intolerance (IGT), or obese and newly diagnosed with type 2 diabetes, for faecal microbiota transplant (FMT) into germ-free (GF) B6 mice and we assessed IgM-bound bacteria and immune responses. Compared with wild-type mice, Aid−/− B6 mice developed exacerbated HFDIO due to abundant levels of IgM. FMT from Aid−/− B6 to GF B6 mice promoted greater weight gain in recipient mice compared with FMT using wild-type mouse faecal microbiota. Obese youth with type 2 diabetes had more IgM-bound gut bacteria. Using the stools from the obese youth with type 2 diabetes for FMT to GF B6 mice, we observed that the gut microbiota promoted body weight gain and impaired glucose tolerance in the recipient GF B6 mice. Importantly, some clinical features of these obese young individuals were mirrored in the GF B6 mice following FMT. Our results suggest that IgM-bound gut microbiota may play an important role in the immuno-pathogenesis of obesity and type 2 diabetes, and provide a novel link between IgM in obesity and type 2 diabetes in both mice and humans. The 16s rRNA sequencing datasets supporting the current study have been deposited in the NCBI SRA public repository (https://www.ncbi.nlm.nih.gov/sra; accession no. SAMN18796639). The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-022-05711-8.
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DOI：
10.1126/science.1241214
发表时间：
2013-09-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ridaura VK;Faith JJ;Rey FE;Cheng J;Duncan AE;Kau AL;Griffin NW;Lombard V;Henrissat B;Bain JR;Muehlbauer MJ;Ilkayeva O;Semenkovich CF;Funai K;Hayashi DK;Lyle BJ;Martini MC;Ursell LK;Clemente JC;Van Treuren W;Walters WA;Knight R;Newgard CB;Heath AC;Gordon JI
通讯作者：
Gordon JI
DOI：
10.4049/jimmunol.1601031
发表时间：
2017-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kosaraju R;Guesdon W;Crouch MJ;Teague HL;Sullivan EM;Karlsson EA;Schultz-Cherry S;Gowdy K;Bridges LC;Reese LR;Neufer PD;Armstrong M;Reisdorph N;Milner JJ;Beck M;Shaikh SR
通讯作者：
Shaikh SR
影响因子：
64.5
作者：
Revy, P;Muto, T;Durandy, A
通讯作者：
Durandy, A
影响因子：
16.6
作者：
Jackson-Jones, Lucy H.;Duncan, Sheelagh M.;Magalhaes, Marlene S.;Campbell, Sharon M.;Maizels, Rick M.;McSorley, Henry J.;Allen, Judith E.;Benezech, Cecile
通讯作者：
Benezech, Cecile
影响因子：
46.9
作者：
通讯作者：
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