Microbial dispersal, skin-to-skin contact, and assembly of the neonatal gut microbiome

微生物扩散、皮肤接触以及新生儿肠道微生物组的组装

• 批准号: 10178070
• 负责人: DAVID A. RELMAN
• 金额: $ 11.83万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10178070
• 关键词: 16S ribosomal RNA sequencing; Affect; Age; Antibiotic Therapy; Antibiotics; Automobile Driving; Birth; Blood specimen; Caring; Cells; Child; Collection; Communities; Complex; Cytometry; Data; Development; Digestion; Disease; Ensure; Environment; Event; Evolution; Exposure to; Frequencies; Goals; Health; High-Throughput Nucleotide Sequencing; Human; Human Microbiome; Immune; Immune system; Infant; Intervention; Life; Measurement; Measures; Mediating; Modeling; Nature; Neonatal; Neonatal Intensive Care Units; Newborn Infant; Outcome; Parents; Pediatric Hospitals; Physiological; Physiology; Process; Recovery; Research; Resistance; Resistance to infection; Role; Sampling; Services; Shapes; Shotguns; Skin; Source; Systems Development; Testing; Time; Variant; base; dysbiosis; effective intervention; experience; fecal microbiome; gut microbiome; improved; indigenous community; metagenome; metagenomic sequencing; microbial; microbial community; microbiome; microbiome research; microorganism; migration; neonatal health; pathogen; postnatal development; rRNA Genes; resilience; theories; therapy design; trait; transmission process

The microbial communities associated with humans, referred to as the human microbiome, provide many important beneficial services to their hosts. Yet, despite their importance, we still know very little about the fundamental processes shaping microbial community formation. Understanding the assembly of microbiomes in newborns following birth is necessary for the design of interventions that manipulate them to improve health and development. Broadly, microbiome assembly is believed to be a product of microbial dispersal and selection by the host, both of which are likely disrupted for newborns in neonatal intensive care units (NICUs). NICUs provide a hygienic environment with relatively limited opportunities for the transmission of commensal microorganisms, and the impact of host selection on resident microbiomes is likely affected by the altered physiology and underdeveloped state of newborns in NICUs. Characterizing the effects of factors that potentially increase the dispersal of commensals, such as skin-to-skin contact care between parents and newborns, or that alter the nature of host selection, such as the development of the immune system, will provide us with a deeper understanding of microbiome assembly in early life. We propose to study the assembly of newborn microbiomes in NICUs, with a focus on the interactive effects of the development of the immune system, skin-to-skin contact care, and microbial dispersal. We will characterize the composition of newborn fecal microbiomes in the NICU using high-throughput 16S rRNA gene and shotgun metagenomic sequencing at multiple time points: just after birth, before and after antibiotic use, and just before transitioning out of the NICU, in addition to regular intervals in between. We will also characterize the immune cell profiles of newborns using mass cytometry on blood samples taken at regular intervals, as well as record the frequency and duration of skin-to-skin contact between parents and infants, and antibiotic use. Using these combined data, we will first determine the relationship between the assembly of newborn microbiomes and the development of the immune system and identify the features that most strongly determine the strength of this relationship. We will then determine the effect of skin-to-skin contact on newborn microbiomes and test the hypothesis that increases in skin-to-skin contact are correlated with increases in microbiome diversity, stability, and the rate of recovery from antibiotics. In addition, we will also test the hypothesis that skin-to-skin contact mediates the relationship between microbiome assembly and immune development. Finally, using ecological theory and dispersal-based community assembly models, we will estimate microbial migration rates and measure the contribution of microbial dispersal to microbiome assembly relative to other factors. By elucidating the ecological mechanisms driving the assembly of newborn microbiomes in NICUs, this research has the potential to inform safe and effective intervention strategies to ensure the transmission and development of healthy microbiomes in newborns.

与人类相关的微生物群落，被称为人类微生物群，为宿主提供许多重要的有益服务。然而，尽管它们很重要，我们仍然对微生物群落形成的基本过程知之甚少。了解新生儿出生后微生物群的组装情况对于设计干预措施以改善健康和发育是必要的。广泛地说，微生物组的组装被认为是宿主微生物扩散和选择的产物，这两个过程都可能对新生儿重症监护病房(NICU)中的新生儿造成干扰。NICU提供了一个卫生的环境，但传播共生微生物的机会相对有限，宿主选择对NICU中驻留微生物群的影响可能受到NICU中新生儿生理变化和不发达状态的影响。确定可能增加共生体扩散的因素(如父母和新生儿之间的皮肤接触护理)的影响，或改变宿主选择性质的因素(如免疫系统的发育)的影响，将为我们提供对早期生命中微生物群组装的更深层次的理解。我们建议研究新生儿微生物群在NICU中的组装，重点放在免疫系统发展、皮肤接触护理和微生物传播的交互作用上。我们将在多个时间点使用高通量16S rRNA基因和鸟枪元基因组测序来表征NICU中新生儿粪便微生物群的组成：出生后、使用抗生素之前和之后，以及在过渡出NICU之前，以及之间有规律的间隔。我们还将定期采集血液样本，使用质量细胞仪分析新生儿的免疫细胞特征，并记录两人皮肤接触的频率和持续时间。 父母和婴儿，以及抗生素的使用。使用这些组合数据，我们将首先确定新生儿微生物群组装和免疫系统发育之间的关系，并确定最强烈地决定这种关系强度的特征。然后，我们将确定皮肤接触对新生儿微生物群的影响，并检验皮肤接触增加与微生物群多样性、稳定性和抗生素恢复率增加相关的假设。此外，我们还将检验皮肤接触调节微生物组组装和免疫发育之间关系的假设。最后，利用生态学理论和基于分散的群落组装模型，我们将估计微生物的迁移速率，并测量相对于其他因素，微生物分散对微生物群落组装的贡献。通过阐明驱动新生儿微生物群在NICU中聚集的生态机制，本研究有可能提供安全有效的干预策略，以确保健康微生物群在新生儿中的传播和发展。