Altered Stool Microbiota of Infants with Cystic Fibrosis Shows a Reduction in Genera Associated with Immune Programming from Birth
Altered Stool Microbiota of Infants with Cystic Fibrosis Shows a Reduction in Genera Associated with Immune Programming from Birth
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DOI：
10.1128/jb.00274-19
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发表时间：
2019-08-01
影响因子：
3.2
通讯作者：
Madan, Juliette C.
中科院分区：
文献类型：
--
作者：
Antosca, Katherine M.;Chernikova, Diana A.;Madan, Juliette C.
本小组先前的工作表明，囊性纤维化（CF）婴儿的胃肠道微生物群与该人群的气道疾病之间存在关联。在这里，我们报告了CF婴儿的粪便微生物群在生命的第一年显示出个体内细菌多样性（α多样性）的改变，但在很大程度上没有变化，与没有CF的婴儿（对照队列）相比，在第一年显示出预期的α多样性增加。这两个队列的β多样性，或样本间多样性，在第一年的生命中有显著差异，并且在统计学上与气道恶化显著相关，证实了我们早期的发现。与对照组婴儿相比，CF婴儿早在出生6周时，类杆菌（一种与免疫调节相关的细菌属）的水平就降低了，并且CF队列中类杆菌的显著降低持续了整个第一年的生命。只有另外两个属在第一年有显著差异：Roseburia显著减少，Veillonella显著增加。其他属在两个队列之间显示差异，但仅在选定的时间点。体外研究表明，将极化肠细胞系的顶面暴露于拟杆菌属的上清液中可显著降低白细胞介素8 （IL-8）的产生，这表明肠道微生物群的变化可能影响CF的炎症。CF患儿的气道疾病，并提供了从生命早期开始进行治疗干预的潜在机会。越来越多的证据表明，CF患者的胃肠道细菌群落与气道疾病进展之间存在联系
Previous work from our group indicated an association between the gastrointestinal microbiota of infants with cystic fibrosis (CF) and airway disease in this population. Here we report that stool microbiota of infants with CF demonstrates an altered but largely unchanging within-individual bacterial diversity (alpha diversity) over the first year of life, in contrast to the infants without CF (control cohort), which showed the expected increase in alpha diversity over the first year. The beta diversity, or between-sample diversity, of these two cohorts was significantly different over the first year of life and was statistically significantly associated with airway exacerbations, confirming our earlier findings. Compared with control infants, infants with CF had reduced levels of Bacteroides, a bacterial genus associated with immune modulation, as early as 6 weeks of life, and this significant reduction of Bacteroides spp. in the cohort with CF persisted over the entire first year of life. Only two other genera were significantly different across the first year of life: Roseburia was significantly reduced and Veillonella was significantly increased. Other genera showed differences between the two cohorts but only at selected time points. In vitro studies demonstrated that exposure of the apical face of polarized intestinal cell lines to Bacteroides species supernatants significantly reduced production of interleukin 8 (IL-8), suggesting a mechanism whereby changes in the intestinal microbiota could impact inflammation in CF. This work further establishes an association between gastrointestinal microbiota, inflammation, and airway disease in infants with CF and presents a potential opportunity for therapeutic interventions beginning in early life.IMPORTANCE There is growing evidence for a link between gastrointestinal bacterial communities and airway disease progression in CF. We demonstrate that infants with CF