Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification.

Low-dose penicillin exposure in early life decreases Th17 and the susceptibility to DSS colitis in mice through gut microbiota modification.
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生命早期接触低剂量青霉素可通过改变肠道微生物群来降低小鼠的 Th17 和 DSS 结肠炎的易感性

DOI:
10.1038/srep43662
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发表时间:
2017-03-08
期刊:
影响因子:
4.6
通讯作者:
Zheng Q
Zheng Q
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jin S;Zhao D;Cai C;Song D;Shen J;Xu A;Qiao Y;Ran Z;Zheng Q

文献摘要

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在生命早期暴露于抗生素会导致肠道微生物群的显著变化,并可能导致炎症性肠病(IBD)的后期发作。然而,根据流行病学研究的矛盾结果,早期抗生素治疗与IBD之间的关系是模糊的。在本研究中,我们证明了低剂量青霉素预处理对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎具有独特的保护作用。低剂量青霉素还抑制了各种肠组织中促炎细胞因子IL-17的表达,并减少了小肠固有层中Th 17细胞的数量。甲硝唑和恩诺沙星都没有类似的效果。我们进一步证实,低剂量青霉素可以引起肠道微生物群的特定变化,特别是消除分节丝状菌(SFB)。未接种SFB的小鼠在接受青霉素或水治疗时没有表现出差异。总之,结果表明,低剂量青霉素可以实现对敏感细菌的高度特异性操作,并干扰生命早期肠道免疫系统的发育。该研究可能进一步表明,通过微调肠道微生物群,在某些IBD或其他自身免疫性疾病患者群体中实现良好免疫状态的可能性。
Antibiotic exposure in early life can lead to a significant change of the gut microbiota and may contribute to later onset of inflammatory bowel disease (IBD). However, the relationship between early-life antibiotic treatment and IBD is ambiguous, according to contradicting results of epidemiologic studies. In the present study, we demonstrated that low-dose penicillin pre-treatment had a unique protective effect against mouse colitis induced by dextran sodium sulfate (DSS). Low-dose penicillin also suppressed the expression of pro-inflammatory cytokine IL-17 in various intestinal tissues, and decreased the amount of Th17 cells in small-intestine lamina propria. Neither metronidazole nor enrofloxacin had a similar effect. We further confirmed that low-dose penicillin could cause specific changes of the gut microbiota, especially the eradication of segmented filamentous bacteria (SFB). Mice without SFB inoculation showed no disparity when treated with penicillin or water. Taken together, the results showed that low-dose penicillin can achieve a highly specific manipulation of sensitive bacteria and interfere with development of intestinal immune system in early life. The study may further indicate the possibility of achieving a favorable immune state among a certain group of patients with IBD, or other autoimmune diseases, by fine-tuning the gut microbiota.