Functional consequences of bacterial-fungal dysbiosis in E/VLBW infants

摘要 细菌在人类肠道微生物群中提供重要的功能(例如，代谢能力)； 然而，古生物和微型真核生物(真菌和原生动物)产生的重要影响才刚刚开始。 有待探索。这些多微生物相互作用有助于调节机会主义的扩张和过度生长 并在塑造免疫反应方面发挥重要作用。例如，真菌群落可以是 在出生期间或从环境中垂直获得，并在塑造 细菌群落的方式尚不完全清楚。极低出生体重(E/VLBW) 早产儿出生时免疫系统非常不成熟，特别容易受到侵袭。 感染，所以他们经常用广谱抗生素和抗真菌药物治疗。这些早产儿 在新生儿重症监护室呆的时间最长，经历各种压力源。这个 广谱抗菌剂的使用可能对发育中的细菌和真菌产生长期影响 在婴儿肠道定居的社区，这反过来可能会影响长期健康。而且因为 肠道微生物组的代谢潜能是原核生物和真核生物相互作用的产物 微生物，迫切需要“微生物组”研究纳入更全面的方法 (例如，多组)以捕获影响功能相互作用的基因产物和特征代谢物 网络。我们已经证明，E/VLBW婴儿中的早产儿包括明显的生物失调，很可能 影响关键代谢物特征，这些特征可能影响营养感知和/或卡路里处理能力 可能影响增长和发展的方式。这项研究将利用来自 E/VLBW婴儿，其中许多被跟踪到4岁，通过 元基因组测序和代谢组学。微生物组的早期变化也可能有助于或 易患上日后的健康问题，如代谢障碍和肥胖。我们建议，一个产品的 受干扰的E/VLBW婴儿肠道微生物群与长期健康后果有关，但尚未完全 了解，但可能包括对营养感知、卡路里摄入的代谢过程的影响，以及 在生命的最初几年中，随后的生长。

Abstract Bacteria deliver a significant functionality (e.g., metabolic capability) in the gut microbiome of humans; however, Archaea and microeukaryotes (fungi and protozoans) exert important influences that are only starting to be explored. These polymicrobial interactions help regulate the expansion and overgrowth of opportunistic organisms, and serve important roles in shaping immune responses. Fungal communities, for example, can be acquired vertically during birth or from the environment and serve important roles in shaping the composition of bacterial communities in ways that are not yet fully understood. Extremely and very low birth weight (E/VLBW) preterm infants are born with very immature immune systems and are particularly vulnerable to invasive infections, so they are often treated with broad-spectrum antibiotics and antifungals. These premature infants spend the most amount of time in the neonatal intensive care units and experience a variety of stressors. The use of broad-spectrum antimicrobials likely has long-term impacts on the developing bacterial and fungal communities that colonize the infant gut, and this in turn may impact long-term health. And because the metabolic potential of the gut microbiome is a product of the interactions of prokaryotic and eukaryotic microbes, there is an urgent need for ‘microbiome’ studies to incorporate more comprehensive approaches (e.g., multi-omic) to capture the gene products and signature metabolites impacting functional interaction networks. We have shown that prematurity among E/VLBW infants includes a significant dysbiosis that likely impacts key metabolite signatures that may influence nutrient sensing and/or calorie processing capabilities, in ways that can impact growth and development. This study will leverage banked temporal stool samples from E/VLBW infants, many of which were followed until the age of 4, to evaluate functional metabolic networks via metagenomic sequencing and metabolomics. Early changes to the microbiome may also contribute to or predispose later health, such as metabolic dysfunction and obesity. We propose that the products of a perturbed E/VLBW infant gut microbiome are linked to long-term health consequences that are not yet fully understood, but likely include effects on nutrient sensing, metabolic processing of caloric intake, and subsequent growth in the first few years of life.