Center for Research on the Respiratory Microbiota of African Children (ReMAC)

非洲儿童呼吸道微生物区系研究中心 上呼吸道的微生物区系(微生物群落)在肺炎的发生发展中起着关键作用。 儿童下呼吸道感染(LRTI)大多数重要的细菌性LRTI病原体也会定居 鼻咽(NP)，它通常是儿童下呼吸道感染的感染源，也是宿主 传给其他孩子。我们已经召集了调查人员之间的跨学科合作 在南非、冈比亚和马拉维的三个领先的非洲研究机构，以及一个领先的基因组 研究决定因素、成分和生物学意义的关键问题 非洲儿童上呼吸道的微生物区系。我们将利用几个现有的大型队列和样本 进行三个互补但不相互依赖的研究项目的储存库，每个项目都在多个 非洲网站。第一个项目将集中于对NP微生物区系(细菌、真菌)的全面描述 和病毒成分)在健康的非洲儿童生命的第一年，经常使用纵向的 抽样的队列。我们还将研究NP微生物区系在抵抗殖民方面的作用 呼吸道病原体肺炎链球菌，包括调节疫苗诱导的保护作用。这个 第二个项目将调查NP微生物区系的作用，包括考虑抗菌素耐药性， 非洲儿童下呼吸道感染的发生率、严重性和复发率。第三个项目将检查 季节性、吸入环境暴露(或污染物)、家庭粉尘之间的关系 微生物区系，以及南非和冈比亚儿童的NP和口咽微生物区系。我们 将使用扩增子测序来定义微生物区系的细菌和真菌成分，即靶向核 病毒成分的酸扩增测试和补充的鸟枪式元基因组测序， 验证和扩展我们的发现。我们将应用统计建模工具，包括那些源自生态学的工具， 了解微生物区系的演化、相互作用和决定因素。 我们将建立一个非洲儿童呼吸微生物区系研究中心(ReMAC)，该中心将 通过建立一个可持续的合作网络，在非洲建立呼吸微生物区系研究能力 非洲和美国调查人员，重点是专门培训、研究生学习、技术转让和 职业发展。成功完成建议的工作，将会加深我们对 鼻咽部生态学和下呼吸道感染的发病机制，促进诊断或治疗的发展 LRTI儿童的预后工具，提供了对微生物区系的治疗性操作的洞察 可能是可取的，并确定可修改的风险因素，这些因素对 微生物区系。 第1条

Center for Research on the Respiratory Microbiota of African Children (ReMAC): Abstract The microbiota (community of microorganisms) of the upper airways plays a key role in the development of lower respiratory tract infection (LRTI) in children. Most of the important bacterial LRTI pathogens also colonize the nasopharynx (NP), which often serves as the source of infection for LRTI in a child as well as the reservoir for transmission to other children. We have assembled an interdisciplinary collaboration between investigators at three leading African research institutions, in South Africa, The Gambia and Malawi, and a leading genomic center in the USA to address key questions on the determinants, composition and biological significance of the microbiota of the upper airways in African children. We will leverage several large existing cohorts and sample repositories to conduct three complementary but not co-dependent research projects, each done at multiple African sites. The first project will focus on comprehensive description of the NP microbiota (bacterial, fungal and viral components) in healthy African children over the first year of life, using longitudinal, frequently sampled cohorts. We will also study the role of the NP microbiota in resistance to colonization with the respiratory pathogen, Streptococcus pneumoniae, including modulation of vaccine-induced protection. The second project will investigate the role of the NP microbiota, including consideration of antimicrobial resistance, in the incidence, severity, and recurrence of LRTI in African children. The third project will examine the association between seasonality, inhaled environmental exposures (or pollutants), the household dust microbiota, and the microbiota of the NP and oropharynx in children from South Africa and The Gambia. We will use amplicon sequencing to define the bacterial and fungal components of the microbiota, targeted nucleic acid amplification testing for the viral component, and shotgun metagenomic sequencing to complement, validate and extend our findings. We will apply statistical modeling tools, including those derived from ecology, to understand the evolution of, interactions within, and determinants of, the microbiota. We will develop a Center for Research into the Respiratory Microbiota of African Children (ReMAC) which will build capacity for respiratory microbiota research in Africa, by establishing a sustainable, collaborative network of African and US investigators, with focus on specialized training, postgraduate study, technology transfer and career development. Successful completion of the proposed work will enhance our understanding of the ecology of the nasopharynx and of the pathogenesis of LRTI, promote the development of diagnostic or prognostic tools for children with LRTI, provide insight into whether therapeutic manipulation of the microbiota may be desirable and identify modifiable risk factors which negatively influence the composition of the microbiota.   1