Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, USA.
Department of Pediatrics, Children's Hospital at Dartmouth, Dartmouth Health , Lebanon, New Hampshire, USA.
mSphere. 2023 Aug 24;8(4):e0004623. doi: 10.1128/msphere.00046-23. Epub 2023 Jul 5.
Cystic fibrosis (CF) is a heritable disease that causes altered physiology at mucosal sites; these changes result in chronic infections in the lung, significant gastrointestinal complications as well as dysbiosis of the gut microbiome, although the latter has been less well explored. Here, we describe the longitudinal development of the gut microbiome in a cohort of children with CF (cwCF) from birth through early childhood (0-4 years of age) using 16S rRNA gene amplicon sequencing of stool samples as a surrogate for the gut microbiota. Similar to healthy populations, alpha diversity of the gut microbiome increases significantly with age, but diversity plateaus at ~2 years of age for this CF cohort. Several taxa that have been associated with dysbiosis in CF change with age toward a more healthy-like composition; notable exceptions include , which decreases with age, and , which increases with age. We also examined the relative abundance and prevalence of nine taxa associated with CF lung disease, several of which persist across early life, highlighting the possibility of the lung being seeded directly from the gut early in life. Finally, we applied the Crohn's Dysbiosis Index to each sample, and found that high Crohn's-associated dysbiosis early in life (<2 years) was associated with significantly lower in samples collected from 2 to 4 years of age. Together, these data comprise an observational study that describes the longitudinal development of the CF-associated gut microbiota and suggest that early markers associated with inflammatory bowel disease may shape the later gut microbiota of cwCF. IMPORTANCE Cystic fibrosis is a heritable disease that disrupts ion transport at mucosal surfaces, causing a buildup of mucus and dysregulation of microbial communities in both the lungs and the intestines. Persons with CF are known to have dysbiotic gut microbial communities, but the development of these communities over time beginning at birth has not been thoroughly studied. Here, we describe an observation study following the development of the gut microbiome of cwCF throughout the first 4 years of life, during the critical window of both gut microbiome and immune development. Our findings indicate the possibility of the gut microbiota as a reservoir of airway pathogens and a surprisingly early indication of a microbiota associated with inflammatory bowel disease.
囊性纤维化（CF）是一种遗传性疾病，会导致黏膜部位的生理改变；这些变化导致肺部慢性感染、严重的胃肠道并发症以及肠道微生物组的失调，尽管后者研究较少。在这里，我们通过粪便样本 16S rRNA 基因扩增子测序来描述一组 CF 患儿（cwCF）从出生到幼儿期（0-4 岁）的肠道微生物组的纵向发展，以此作为肠道微生物组的替代物。与健康人群相似，肠道微生物组的α多样性随着年龄的增长显著增加，但对于这个 CF 队列，多样性在 2 岁左右达到平台期。一些与 CF 中失调相关的分类群随着年龄的增长向更健康的组成方向变化；值得注意的例外包括，随着年龄的增长而减少，和，随着年龄的增长而增加。我们还检查了与 CF 肺部疾病相关的九个分类群的相对丰度和流行率，其中几个在整个幼儿期都持续存在，这突出了肺部可能在生命早期直接从肠道播种的可能性。最后，我们对每个样本应用了克罗恩病失调指数，发现生命早期（<2 岁）高克罗恩病相关失调与 2 至 4 岁时采集的样本中的显著降低相关。综上所述，这些数据构成了一项观察性研究，描述了 CF 相关肠道微生物组的纵向发展，并表明与炎症性肠病相关的早期标志物可能会影响 cwCF 的后期肠道微生物组。重要性囊性纤维化是一种遗传性疾病，它会破坏黏膜表面的离子转运，导致肺部和肠道中的黏液积聚和微生物群落失调。已知 CF 患者存在肠道微生物群落失调，但从出生开始随着时间的推移这些群落的发展尚未得到彻底研究。在这里，我们描述了一项观察性研究，即 cwCF 在生命的前 4 年中肠道微生物组的发展情况，这是肠道微生物组和免疫系统发育的关键窗口期。我们的研究结果表明，肠道微生物组可能是气道病原体的储库，也是与炎症性肠病相关的微生物组的一个惊人的早期指标。
