Bifidobacteria-mediated immune system imprinting early in life

被引:490
作者
Henrick, Bethany M. [1 ,2 ]
Rodriguez, Lucie [3 ]
Lakshmikanth, Tadepally [3 ]
Pou, Christian [3 ]
Henckel, Ewa [3 ,4 ,5 ]
Arzoomand, Aron [3 ]
Olin, Axel [3 ]
Wang, Jun [3 ]
Mikes, Jaromir [3 ]
Tan, Ziyang [3 ]
Chen, Yang [3 ]
Ehrlich, Amy M. [1 ]
Bernhardsson, Anna Karin [3 ]
Mugabo, Constantin Habimana [3 ]
Ambrosiani, Ylva [4 ]
Gustafsson, Anna [4 ,5 ]
Chew, Stephanie [1 ]
Brown, Heather K. [1 ]
Prambs, Johann [1 ]
Bohlin, Kajsa [4 ,5 ]
Mitchell, Ryan D. [1 ]
Underwood, Mark A. [6 ,7 ]
Smilowitz, Jennifer T. [6 ,8 ]
German, J. Bruce [6 ,8 ]
Frese, Steven A. [2 ,9 ]
Brodin, Petter [3 ,10 ]
机构
[1] Evolve BioSyst Inc, Davis, CA 95618 USA
[2] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68588 USA
[3] Karolinska Inst, Dept Womens & Childrens Hlth, Sci Life Lab, S-17121 Solna, Sweden
[4] Karolinska Inst, Dept Clin Sci Intervent & Technol, S-14152 Stockholm, Sweden
[5] Karolinska Univ Hosp, Dept Neonatol, S-14186 Stockholm, Sweden
[6] Univ Calif Davis, Foods Hlth Inst, Davis, CA 95616 USA
[7] Univ Calif Davis, Childrens Hosp, Dept Pediat, Sacramento, CA 95817 USA
[8] Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA
[9] Univ Nevada, Dept Nutr, Reno, NV 89557 USA
[10] Karolinska Univ Hosp, Pediat Rheumatol, S-17176 Solna, Sweden
基金
瑞典研究理事会; 欧洲研究理事会;
关键词
LONGUM SUBSP INFANTIS; GUT MICROBIOTA; MILK UTILIZATION; T-CELLS; SEQUENCE; IMMUNOBIOLOGY; ACTIVATION; EXPRESSION; DIVERSITY; DYSBIOSIS;
D O I
10.1016/j.cell.2021.05.030
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Bifido-bacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon beta (IFN beta) 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.
引用
收藏
页码:3884 / +
页数:26
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