Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes.
Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes.
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早期生命中的抗生素改变了肠道微生物组并增加了自身免疫胰岛素依赖性糖尿病的自发小鼠模型。
DOI：
10.1371/journal.pone.0125448
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chatenoud L
中科院分区：
文献类型：
--
作者：
Candon S;Perez-Arroyo A;Marquet C;Valette F;Foray AP;Pelletier B;Milani C;Ventura M;Bach JF;Chatenoud L
胰岛素依赖型或 1 型糖尿病是一种典型的自身免疫性疾病，过去几十年来，工业化国家的发病率稳步上升。最近的证据表明肠道微生物群对于解释这一趋势非常重要。在这里，自发发展为自身免疫 1 型糖尿病的非肥胖糖尿病 (NOD) 小鼠接受了不同的抗生素治疗，以探索有针对性的肠道菌群失调对疾病进展的影响。从受孕那一刻起，口服广谱抗生素混合物（即链霉素、粘菌素和氨苄青霉素）或单独使用万古霉素，治疗繁殖配对，并在产后和成年期间直至 40 周随访结束。在用这两种抗生素疗法治疗后，雄性小鼠的糖尿病发病率显着且类似地增加。在 NOD 雌性中，观察到疾病发病率有轻微但不显着的增加趋势。通过对细菌 16S rRNA 基因的 V3 区域进行测序来评估肠道微生物群组成的变化。抗生素混合物的施用导致肠道微生物群几乎完全消融。与对照小鼠相比，万古霉素治疗导致大肠埃希氏菌属、乳杆菌属和沙氏菌属增加，梭状芽胞杆菌目、毛螺菌科、普氏菌科和理肯氏菌科成员减少。在万古霉素处理的小鼠的回肠和结肠固有层中观察到产生 IL-17 的细胞、CD4+TCRαβ+ 和 TCRγδ+ T 细胞的大量消除。这些结果表明，万古霉素诱导的肠道微生物群的定向甚至部分消融会显着增加雄性 NOD 小鼠的 1 型糖尿病发病率，因此提示孕妇和新生儿在使用抗生素时应谨慎。
Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD) mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin) or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.
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DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
5
作者：
Hviid, Anders;Svanstrom, Henrik
通讯作者：
Svanstrom, Henrik
影响因子：
4.8
作者：
FITZPATRICK, F;LEPAULT, F;DARDENNE, M
通讯作者：
DARDENNE, M
影响因子：
3.7
作者：
Aumeunier A;Grela F;Ramadan A;Pham Van L;Bardel E;Gomez Alcala A;Jeannin P;Akira S;Bach JF;Thieblemont N
通讯作者：
Thieblemont N
影响因子：
15.3
作者：
FOX, HS
通讯作者：
FOX, HS