Journal
CELL HOST & MICROBE
Volume 27, Issue 6, Pages 899-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2020.04.008
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Funding
- GSK
- NIH [DK30292]
- Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust, UK [096100]
- Thought Leader award from Agilent Technologies
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Undernourished children in low-income countries often exhibit poor responses to oral vaccination. Perturbed microbiota development is linked to undernutrition, but whether and how microbiota changes affect vaccine responsiveness remains unclear. Here, we show that gnotobiotic mice colonized withmicrobiota from undernourished Bangladeshi children and fed a Bangladeshi diet exhibited microbiota-dependent differences in mucosal IgA responses to oral vaccination with cholera toxin (CT). Supplementation with a nutraceutical consisting of spirulina, amaranth, flaxseed, and micronutrients augmented CT-IgA production. Mice initially colonized with a microbiota associated with poor CT responses exhibited improved immunogenicity upon invasion of bacterial taxa from cagemates colonized with a more responsive'' microbiota. Additionally, a consortium of five cultured bacterial invaders conferred augmented CT-IgA responses in mice fed the supplemented diet and colonized with the hypo-responsive'' community. These results provide preclinical proof-of-concept that diet and microbiota influencemucosal immune responses to CT vaccination and identify a candidate synbiotic formulation.
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