Maternal gut microbiome regulates immunity to RSV infection in offspring

被引:30
作者
Fonseca, Wendy [1 ]
Malinczak, Carrie-Anne [1 ]
Fujimura, Kei [2 ]
Li, Danny [2 ]
McCauley, Kathryn [2 ]
Li, Jia [3 ]
Best, Shannon K. K. [1 ]
Zhu, Diana [1 ]
Rasky, Andrew J. [1 ]
Johnson, Christine C. [3 ]
Bermick, Jennifer [4 ]
Zoratti, Edward M. [5 ]
Ownby, Dennis [6 ]
Lynch, Susan, V [2 ]
Lukacs, Nicholas W. [1 ,7 ]
Ptaschinski, Catherine [1 ,7 ]
机构
[1] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[2] Univ Calif San Francisco, Dept Med Gastroenterol, San Francisco, CA 94143 USA
[3] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA
[4] Univ Michigan, Dept Pediat, Div Neonatal Perinatal Med, Ann Arbor, MI 48109 USA
[5] Henry Ford Hlth Syst, Div Allergy & Clin Immunol, Dept Med, Detroit, MI USA
[6] Augusta Univ, Dept Pediat, Augusta, GA USA
[7] Univ Michigan, Mary H Weiser Food Allergy Ctr, Ann Arbor, MI 48109 USA
基金
美国国家卫生研究院;
关键词
SYNCYTIAL-VIRUS BRONCHIOLITIS; EARLY-LIFE; ASTHMA; CELLS; BACTERIA; ALLERGY; AGE; METABOLITES; CYTOKINES; STRAINS;
D O I
10.1084/jem.20210235
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.
引用
收藏
页数:15
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