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Bifidobacteria-mediated immune system imprinting early in life
Cell ( IF 45.5 ) Pub Date : 2021-06-17 , DOI: 10.1016/j.cell.2021.05.030
Bethany M Henrick 1 , Lucie Rodriguez 2 , Tadepally Lakshmikanth 2 , Christian Pou 2 , Ewa Henckel 3 , Aron Arzoomand 2 , Axel Olin 2 , Jun Wang 2 , Jaromir Mikes 2 , Ziyang Tan 2 , Yang Chen 2 , Amy M Ehrlich 4 , Anna Karin Bernhardsson 2 , Constantin Habimana Mugabo 2 , Ylva Ambrosiani 5 , Anna Gustafsson 6 , Stephanie Chew 4 , Heather K Brown 4 , Johann Prambs 4 , Kajsa Bohlin 6 , Ryan D Mitchell 4 , Mark A Underwood 7 , Jennifer T Smilowitz 8 , J Bruce German 8 , Steven A Frese 9 , Petter Brodin 10
Affiliation  

Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host’s immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon β (IFNβ) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.



中文翻译:

双歧杆菌介导的免疫系统在生命早期留下印记

生命早期的免疫微生物相互作用会影响过敏、哮喘和其他炎症性疾病的风险。母乳喂养通过为特殊微生物提供营养,进而有益于宿主的免疫系统,从而引导更健康的免疫微生物关系。这种细菌与人类共同进化,但现在在现代社会中越来越少见。在这里,我们表明双歧杆菌的缺乏,特别是宏基因组中人乳寡糖 (HMO) 利用所需基因的消耗,与生命早期的全身炎症和免疫失调有关。在母乳喂养的婴儿中给予婴儿双歧杆菌表达所有 HMO 使用基因的 EVC001、肠道 T 辅助细胞 2 (Th2) 和 Th17 细胞因子被沉默并诱导干扰素 β (IFNβ)。来自补充了 EVC001 的婴儿的粪便中含有丰富的吲哚乳酸和婴儿双歧杆菌衍生的吲哚-3-乳酸 (ILA) 在极化期间上调 Th2 和 Th17 细胞中的免疫调节半乳糖凝集素-1,在第一阶段提供有益微生物和免疫调节之间的功能联系几个月的生命。

更新日期:2021-07-22
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