Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Department of Microbiology, University of Washington, Seattle, WA, USA.
BMC Microbiol. 2021 Sep 15;21(1):247. doi: 10.1186/s12866-021-02305-z.
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.
囊性纤维化（CF）患儿存在胃肠道（GI）并发症，包括胰腺功能不全和肠道炎症，这些并发症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 患儿的粪便微生物群分类组成发生了改变，其特征是与 GI 健康和营养相关的分类群丰度存在差异。此外，CF 低身长婴儿的这些分类差异更为明显，这表明与线性生长失败有潜在联系。我们假设这些差异将导致微生物组功能能力的转变，从而导致 CF 患儿发生炎症和营养衰竭。
为了验证这一假设，我们比较了健康婴儿和 CF 患儿的粪便微生物宏基因组内容，并对 CF 患儿的粪便代谢组进行了分析。与健康婴儿相比，我们在 CF 患儿的粪便微生物功能能力方面发现了显著差异，包括代谢和环境反应功能，并且这些差异在生命的第一年加剧。基于机器学习的 CF 和健康婴儿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，这些差异的特征是 CF 相关的这些功能能力发展延迟。此外，我们发现 CF 患儿的代谢功能相关的功能存在差异，这些差异与饮食和抗生素暴露有关，并且确定了几个可能是这些功能差异潜在驱动因素的分类群。整合宏基因组和代谢组分析进一步表明，粪便 GI 代谢物的丰度与 CF 患儿的营养吸收有关，包括三种胆汁酸，与 CF 患儿中的特定微生物相关。
我们的研究结果突出了几个宏基因组和代谢组因素，包括胆汁酸和其他微生物代谢物，这些因素可能会影响 CF 患儿的营养、生长和 GI 健康。这些因素可能成为基于微生物组的新型治疗方法的有前途的途径，以改善这些婴儿的健康结果。
