Combined Prebiotic and Microbial Intervention Improves Oral Cholera Vaccination Responses in a Mouse Model of Childhood Undernutrition

Blanda Di Luccia, Philip P. Ahern, Nicholas W. Griffin, Jiye Cheng, Janaki L. Guruge, Alexandra E. Byrne, Dmitry A. Rodionov, Semen A. Leyn, Andrei L. Osterman, Tahmeed Ahmed, Marco Colonna, Michael J. Barratt, Nicolas F. Delahaye, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 with microbiota 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 influence mucosal immune responses to CT vaccination and identify a candidate synbiotic formulation.

Original languageEnglish
Pages (from-to)899-908.e5
JournalCell Host and Microbe
Volume27
Issue number6
DOIs
StatePublished - Jun 10 2020

Keywords

  • childhood undernutrition
  • cholera toxin
  • gnotobiotic mouse models
  • human gut microbiota
  • microbial metabolism
  • oral vaccine responses
  • prebiotics
  • probiotics
  • synbiotics

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