早期抗生素导致的菌群失调会破坏吲哚-3-丙酸的产生,并加剧成年后的过敏性气道炎症

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-07-15 DOI:10.1016/j.immuni.2024.06.010
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引用次数: 0

摘要

幼年时期使用抗生素会破坏微生物定植,增加患过敏症和哮喘的风险。我们报告说,早期服用抗生素(EL-Abx)的小鼠更容易受到屋尘螨(HDM)诱发的过敏性气道炎症的影响,而成年后则不会。即使在肠道微生物组恢复正常后,这种易感性仍会保持。EL-Abx降低了吲哚-3-丙酸(IPA)的全身水平,而IPA会诱发肺上皮细胞应激、新陈代谢和线粒体呼吸的长期变化。IPA减少了线粒体呼吸和超氧化物的产生,并改变了趋化因子和细胞因子的产生。因此,早期补充IPA可保护EL-Abx小鼠在成年后免受HDM诱发的过敏性气道炎症的加重。这些结果揭示了EL-Abx可导致肺部过敏性气道炎症的机制,并强调了减轻EL-Abx有害后果的一种可能的预防方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood

Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx.

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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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