Department of Pediatrics, Division of Pediatric Gastroenterology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
J Pediatr Gastroenterol Nutr. 2024 Sep;79(3):695-704. doi: 10.1002/jpn3.12350. Epub 2024 Aug 9.
The gut microbiota plays an important role in childhood growth. Our longitudinal cohort includes children with cystic fibrosis (CwCF) treated with highly effective modulator therapy. We aimed to elucidate early premodulator microbial signatures associated with postmodulator weight for CwCF later in childhood.
Stool samples were collected from CwCF at 13 days to 60 months. Metagenomic sequencing determined differentially abundant taxa. Children with body mass index or weight for length Z-scores within 1 standard deviation of the mean (SD) were considered normal weight, those >1 SD were classified as risk of overweight while children <1 SD were considered undernourished, although no CwCF met this latter criterion here. Multivariate regression models were applied to identify significant associations between metadata and microbial taxonomic relative abundances.
One hundred and eighty-nine stool samples were analyzed from 39 CwCF. We identified statistically significant differences in early microbiome patterns among those at risk of being overweight compared to those who were normal weight when adjusted for age, sex, CF mutation, and early feeding method. Early microbiome was a stronger driver of growth status than current modulator use. Among those at risk of overweight, several taxa that were consistently in lower abundance included Eggerthella lentha, Ruminococcus, Bacteroides, with increase in abundance of Bacteroides stercoris.
The early microbiome strongly predicts growth in the setting of modulator use for CwCF and we identify microbiome signatures associated with risk of being overweight. We highlight the possibility for interventions or early alternations to nutritional guidance for prevention of comorbid complications.
肠道微生物群在儿童生长中起着重要作用。我们的纵向队列包括接受高效调节剂治疗的囊性纤维化（CwCF）患儿。我们旨在阐明与儿童后期调节剂后体重相关的早期调节剂前微生物特征。
从 13 天至 60 个月的 CwCF 中收集粪便样本。宏基因组测序确定了差异丰富的分类群。体重指数或长度 Z 分数在平均值（SD）的 1 个标准差内的儿童被认为是正常体重，大于 1 SD 的儿童被归类为超重风险，而小于 1 SD 的儿童被认为是营养不良，尽管这里没有 CwCF 符合后者标准。多元回归模型用于确定元数据和微生物分类相对丰度之间的显著关联。
从 39 例 CwCF 中分析了 189 个粪便样本。当调整年龄、性别、CF 突变和早期喂养方法时，与正常体重相比，超重风险的儿童早期微生物组模式存在统计学显著差异。早期微生物组是生长状况的更强驱动因素，而不是当前调节剂的使用。在超重风险的儿童中，一些丰度持续较低的分类群包括 Eggerthella lentha、Ruminococcus、Bacteroides，而 Bacteroides stercoris 的丰度增加。
在 CwCF 使用调节剂的情况下，早期微生物组强烈预测生长，并且我们确定了与超重风险相关的微生物组特征。我们强调了干预或早期改变营养指导以预防合并症并发症的可能性。
