Infants with cystic fibrosis (CF) suffer from gastrointestinal (GI) complications, including pancreatic insufficiency and intestinal inflammation, which have been associated with impaired nutrition and growth. Recent evidence identified altered fecal microbiota taxonomic compositions in infants with CF relative to healthy infants that were characterized by differences in the abundances of taxa associated with GI health and nutrition. Furthermore, these taxonomic differences were more pronounced in low length infants with CF, suggesting a potential link to linear growth failure. We hypothesized that these differences would entail shifts in the microbiome’s functional capacities that could contribute to inflammation and nutritional failure in infants with CF. To test this hypothesis, we compared fecal microbial metagenomic content between healthy infants and infants with CF, supplemented with an analysis of fecal metabolomes in infants with CF. We identified notable differences in CF fecal microbial functional capacities, including metabolic and environmental response functions, compared to healthy infants that intensified during the first year of life. A machine learning-based longitudinal metagenomic age analysis of healthy and CF fecal metagenomic functional profiles further demonstrated that these differences are characterized by a CF-associated delay in the development of these functional capacities. Moreover, we found metagenomic differences in functions related to metabolism among infants with CF that were associated with diet and antibiotic exposure, and identified several taxa as potential drivers of these functional differences. An integrated metagenomic and metabolomic analysis further revealed that abundances of several fecal GI metabolites important for nutrient absorption, including three bile acids, correlated with specific microbes in infants with CF. Our results highlight several metagenomic and metabolomic factors, including bile acids and other microbial metabolites, that may impact nutrition, growth, and GI health in infants with CF. These factors could serve as promising avenues for novel microbiome-based therapeutics to improve health outcomes in these infants.

中文翻译：

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患有囊性纤维化的婴儿的粪便功能能力发生了改变，具有潜在的临床和代谢后果

患有囊性纤维化 (CF) 的婴儿患有胃肠道 (GI) 并发症，包括胰腺功能不全和肠道炎症，这与营养和生长受损有关。最近的证据表明，与健康婴儿相比，CF 婴儿的粪便微生物群分类组成发生了变化，其特征在于与胃肠道健康和营养相关的类群丰度存在差异。此外，这些分类学差异在患有 CF 的低身高婴儿中更为明显，这表明与线性生长障碍存在潜在联系。我们假设这些差异将导致微生物组功能能力的变化，这可能导致 CF 婴儿的炎症和营养不良。为了检验这个假设，我们比较了健康婴儿和 CF 婴儿之间的粪便微生物宏基因组含量，并补充了对 CF 婴儿粪便代谢组的分析。我们发现，与出生后第一年强化的健康婴儿相比，CF 粪便微生物功能能力（包括代谢和环境反应功能）存在显着差异。基于机器学习的健康和 CF 粪便宏基因组功能谱的纵向宏基因组年龄分析进一步表明，这些差异的特征在于这些功能能力发展中与 CF 相关的延迟。此外，我们发现与饮食和抗生素暴露相关的 CF 婴儿代谢相关功能的宏基因组差异，并确定了几个分类群是这些功能差异的潜在驱动因素。一项综合宏基因组和代谢组学分析进一步揭示，几种对营养吸收很重要的粪便 GI 代谢物（包括三种胆汁酸）的丰度与 CF 婴儿的特定微生物相关。我们的研究结果强调了几种宏基因组和代谢组学因素，包括胆汁酸和其他微生物代谢物，它们可能会影响 CF 婴儿的营养、生长和胃肠道健康。这些因素可以作为新的基于微生物组的疗法来改善这些婴儿的健康状况的有希望的途径。与 CF 婴儿的特定微生物相关。我们的研究结果强调了几种宏基因组和代谢组学因素，包括胆汁酸和其他微生物代谢物，它们可能会影响 CF 婴儿的营养、生长和胃肠道健康。这些因素可以作为新的基于微生物组的疗法来改善这些婴儿的健康状况的有希望的途径。与 CF 婴儿的特定微生物相关。我们的研究结果强调了几种宏基因组和代谢组学因素，包括胆汁酸和其他微生物代谢物，它们可能会影响 CF 婴儿的营养、生长和胃肠道健康。这些因素可以作为新的基于微生物组的疗法来改善这些婴儿的健康状况的有希望的途径。