Increased bacterial taxonomic and functional diversity is associated with impaired rotavirus vaccine immunogenicity in infants from India and Malawi.
Increased bacterial taxonomic and functional diversity is associated with impaired rotavirus vaccine immunogenicity in infants from India and Malawi.
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DOI：
10.1186/s12866-023-03098-z
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发表时间：
2023-11-18
期刊：
影响因子：
4.2
通讯作者：
Parker, Edward P. K.
中科院分区：
文献类型：
--
作者：
Cunningham-Oakes, Edward;Bronowski, Christina;Chinyama, End;Jere, Khuzwayo C.;Sindhu, Kulandaipalayam Natarajan C.;Kang, Gagandeep;Iturriza-Gomara, Miren;Darby, Alistair C.;Parker, Edward P. K.
在疾病负担最重的中低收入国家，针对严重轮状病毒相关胃肠炎的口服轮状病毒疫苗（ORVs）的免疫原性和有效性受到损害。确定ORV反应受损的危险因素可能有助于确定提高疫苗有效性的策略。在这项研究中，我们在印度和马拉维进行了一项关于ORV免疫原性的前瞻性研究，使用宏基因组测序对6周龄（与第一次口服ORV剂量相符）收集的粪便样本进行了高分辨率的分类分析。然后，我们分析了这些队列中发育中的微生物组的功能能力。微生物组组成在国家之间差异显著，尽管功能容量比分类组成更相似。我们的研究结果证实了先前报道的结果，即ORV非伺服转换器的微生物组在分类组成上比伺服转换器的微生物组更多样化，并且我们还证明了类似的功能能力模式。尽管分类或功能特征丰度是ORV反应的较差预测因子，但我们表明，这些微生物组数据中关联方向的偏差可用于识别跨LMIC婴儿队列的ORV反应的一致标记。我们还强调了来自低收入中等收入国家的内参基因的系统性代表性不足，这限制了我们研究中的功能注释（在途径和酶委员会水平上分别有7%和13%的注释）。总体而言，在印度和马拉维，生命早期较高的微生物组多样性可能是ORV反应受损的标志，而功能能力的整体视角可能隐藏在微生物组的“暗物质”中。在线版本包含补充材料，可在10.1186/s12866-023-03098-z获得。
The immunogenicity and effectiveness of oral rotavirus vaccines (ORVs) against severe rotavirus-associated gastroenteritis are impaired in low- and middle-income countries (LMICs) where the burden of disease is highest. Determining risk factors for impaired ORV response may help identify strategies to enhance vaccine effectiveness. In this study, we use metagenomic sequencing to provide a high-resolution taxonomic analysis of stool samples collected at 6 weeks of age (coinciding with the first ORV dose) during a prospective study of ORV immunogenicity in India and Malawi. We then analyse the functional capacity of the developing microbiome in these cohorts. Microbiome composition differed significantly between countries, although functional capacity was more similar than taxonomic composition. Our results confirm previously reported findings that the developing microbiome is more diverse in taxonomic composition in ORV non-seroconverters compared with seroconverters, and we additionally demonstrate a similar pattern in functional capacity. Although taxonomic or functional feature abundances are poor predictors of ORV response, we show that skews in the direction of associations within these microbiome data can be used to identify consistent markers of ORV response across LMIC infant cohorts. We also highlight the systemic under-representation of reference genes from LMICs that limit functional annotation in our study (7% and 13% annotation at pathway and enzyme commission level, respectively). Overall, higher microbiome diversity in early life may act as marker for impaired ORV response in India and Malawi, whilst a holistic perspective of functional capacity may be hidden in the “dark matter” of the microbiome. The online version contains supplementary material available at 10.1186/s12866-023-03098-z.
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