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.

低收入国家的营养不良儿童通常对口服疫苗反应不佳。受干扰的微生物群发育与营养不良有关，但微生物群变化是否以及如何影响疫苗反应性仍不清楚。在这里，我们展示了来自营养不良的孟加拉国儿童的微生物群定殖并喂食孟加拉国饮食的无菌小鼠在口服霍乱毒素 (CT) 疫苗接种的粘膜 IgA 反应中表现出微生物群依赖性差异。补充由螺旋藻、苋菜、亚麻籽和微量营养素组成的营养保健品可增强 CT-IgA 的产生。最初定植与较差 CT 反应相关的微生物群的小鼠在从具有更“反应性”微生物群的笼友入侵细菌类群时表现出改善的免疫原性。此外，由五种培养的细菌入侵者组成的联盟在喂食补充饮食并定植于“低反应”群落的小鼠中赋予了增强的 CT-IgA 反应。这些结果提供了临床前概念验证，即饮食和微生物群影响对 CT 疫苗接种的粘膜免疫反应，并确定了一种候选的合生元制剂。