OBJECTIVES Patients with Cystic Fibrosis (CF) suffer from pancreatic insufficiency, lipid malabsorption and gastrointestinal complaints, next to progressive pulmonary disease. Altered mucosal homoeostasis due to malfunctioning chloride channels results in an adapted microbial composition of the gastrointestinal and the respiratory tract. Additionally, antibiotic treatment has the potential to distort resident microbial communities dramatically. This study aims to investigate early life development of the gut microbial community composition of children with CF compared to healthy infants and to study the independent effects of antibiotics taking into account other clinical and lifestyle factors. STUDY DESIGN Faecal samples from 20 infants with CF and 45 healthy infants were collected regularly during the first 18 months of life and microbial composition was determined using 16S rRNA based sequencing. RESULTS We observed significant differences in the overall microbiota composition between infants with CF and healthy infants (p<0.001). Akkermansia and Anaerostipes were significantly more abundant in control infants, whereas Streptococci and E. coli were significantly more abundant in infants with CF, also after correction for several clinical factors (p<0.05). Antibiotic use in infants with CF was associated with a lower alpha diversity, a reduced abundance of Bifidobacterium and Bacteroides, and a higher abundance of Enterococcus. CONCLUSION Microbial development of the gut is different in infants with CF compared to healthy infants from the first months of life on, and further deviates over time, in part as a result of antibiotic treatment. The resulting dysbiosis may have significant functional consequences for the microbial ecosystem in CF patients.

中文翻译：

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生命早期肠道微生物群的发育：囊性纤维化和抗生素治疗的影响

目标 囊性纤维化 (CF) 患者患有胰腺功能不全、脂质吸收不良和胃肠道不适，以及进行性肺病。由于氯离子通道发生故障而改变的黏膜稳态导致胃肠道和呼吸道的微生物组成发生变化。此外，抗生素治疗有可能显着扭曲常驻微生物群落。本研究旨在调查与健康婴儿相比，CF 儿童肠道微生物群落组成的早期生命发展，并在考虑其他临床和生活方式因素的情况下研究抗生素的独立影响。研究设计 在生命的前 18 个月内定期收集 20 名 CF 婴儿和 45 名健康婴儿的粪便样本，并使用基于 16S rRNA 的测序确定微生物组成。结果 我们观察到 CF 婴儿和健康婴儿的整体微生物群组成存在显着差异（p<0.001）。Akkermansia 和 Anerostipes 在对照婴儿中的含量显着更高，而链球菌和大肠杆菌在 CF 婴儿中的含量显着更高，同样在对几个临床因素进行校正后（p<0.05）。CF婴儿使用抗生素与α多样性降低、双歧杆菌和拟杆菌丰度降低以及肠球菌丰度增加有关。结论 CF 婴儿的肠道微生物发育与出生后头几个月的健康婴儿不同，并且随着时间的推移进一步偏离，部分原因是抗生素治疗。由此产生的生态失调可能对 CF 患者的微生物生态系统产生重大的功能影响。