Persistent delay in maturation of the developing gut microbiota in infants with cystic fibrosis.
Persistent delay in maturation of the developing gut microbiota in infants with cystic fibrosis.
复制标题
囊性纤维化婴儿正在发育的肠道微生物群的成熟持续延迟。
DOI：
10.1101/2023.05.02.539134
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ross,BenjaminD
中科院分区：
文献类型：
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作者：
Salerno,Paige;Verster,Adrian;Valls,Rebecca;Barrack,Kaitlyn;Price,Courtney;Madan,Juliette;O'Toole,GeorgeA;Ross,BenjaminD
健康的人类婴儿肠道微生物组在出生和成熟之间经历分类组成的定型变化，达到成人样稳定状态。在此期间，微生物群和宿主免疫系统之间的广泛交流有助于以后的健康状况。尽管有许多报道称微生物组成改变与成人疾病之间存在关联，但对儿科疾病中微生物组发育如何改变知之甚少。一种与肠道微生物群组成改变有关的儿科疾病是囊性纤维化（CF），这是一种多器官遗传性疾病，涉及上皮细胞的氯化物分泌受损以及肠道和其他身体部位的炎症加剧。在这里，我们使用鸟枪宏基因组学来分析从出生到超过36个月的几个CF和非CF纵向队列的婴儿粪便微生物群的菌株水平组成和发育动态。我们确定了一组关键物种，其患病率和丰度可重复地定义了非CF婴儿早期生活中的微生物群发育，但在CF婴儿中相对丰度缺失或减少。肠道微生物群组成和动力学的这些CF特异性差异的后果是微生物群成熟的延迟模式，过渡发育阶段的持续巩固，以及随后未能获得类似成年人的稳定微生物群。我们还检测到CF中口腔来源细菌的相对丰度增加和真菌水平较高，这些特征与炎症性肠病中肠道细菌密度降低相关。我们的研究结果定义了CF个体发育过程中肠道微生物群的关键差异，并表明了定向治疗克服微生物群成熟发育延迟的潜力。
The healthy human infant gut microbiome undergoes stereotypical changes in taxonomic composition between birth and maturation to an adult-like stable state. During this time, extensive communication between microbiota and the host immune system contributes to health status later in life. Although there are many reported associations between microbiota compositional alterations and disease in adults, less is known about how microbiome development is altered in pediatric diseases. One pediatric disease linked to altered gut microbiota composition is cystic fibrosis (CF), a multi-organ genetic disease involving impaired chloride secretion across epithelia and heightened inflammation both in the gut and at other body sites. Here, we use shotgun metagenomics to profile the strain-level composition and developmental dynamics of the infant fecal microbiota from several CF and non-CF longitudinal cohorts spanning from birth to greater than 36 months of life. We identify a set of keystone species whose prevalence and abundance reproducibly define microbiota development in early life in non-CF infants, but are missing or decreased in relative abundance in infants with CF. The consequences of these CF-specific differences in gut microbiota composition and dynamics are a delayed pattern of microbiota maturation, persistent entrenchment in a transitional developmental phase, and subsequent failure to attain an adult-like stable microbiota. We also detect the increased relative abundance of oral-derived bacteria and higher levels of fungi in CF, features that are associated with decreased gut bacterial density in inflammatory bowel diseases. Our results define key differences in the gut microbiota during ontogeny in CF and suggest the potential for directed therapies to overcome developmental delays in microbiota maturation.