Associations between Gut Microbial Colonization in Early Life and Respiratory Outcomes in Cystic Fibrosis

Abstract

Objective To examine patterns of microbial colonization of the respiratory and intestinal tracts in early life in infants with cystic fibrosis (CF) and their associations with breastfeeding and clinical outcomes. Study design A comprehensive, prospective longitudinal analysis of the upper respiratory and intestinal microbiota in a cohort of infants and young children with CF followed from birth was performed. Genus-level microbial community composition was characterized using 16S-targeted pyrosequencing, and relationships with exposures and outcomes were assessed using linear mixed-effects models, time-to-event analysis and principal components analysis. Results Sequencing of 120 samples from 13 subjects collected from birth to 34 months revealed relationships between breastfeeding, microbial diversity in the respiratory and intestinal tracts and the timing of onset of respiratory complications, including exacerbations and colonization with Pseudomonas aeruginosa. Fluctuations in the abundance of specific bacterial taxa preceeded clinical outcomes, including a significant decrease in bacteria of the genus Parabacteroides within the intestinal tract prior to the onset of chronic P. aeruginosa colonization. Specific assemblages of bacteria in intestinal samples, but not respiratory samples, were associated with CF exacerbation in early life, indicating that the intestinal microbiome may play a role in lung health. Conclusion Our findings relating breastfeeding to respiratory outcomes, gut diversity to prolonged periods of health, and specific bacterial communities in the gut prior to respiratory complications in CF highlight a connection between the intestinal microbiome and health and point to potential opportunities for antibiotic or probiotic interventions. Further studies in larger cohorts validating these findings are needed.

Abordaje de la fibrosis quística desde la consulta de enfermería. Caso clínico

“…El cftr actúa como canal de cloro y se encuentra en todos los tejidos exocrinos; el defecto en el transporte del ion cloro causa que estos pacientes tengan un sudor salado y conduce a una deshidratación de las secreciones del tracto respiratorio, pancreáticas, hepáticas, intestinales y genitourinarias, aumentando su viscosidad. Además, la alteración del cftr da lugar a un aumento de la reabsorción de sodio y cloro que está acompañado de una reabsorción pasiva de agua y produce deshidratación de la superficie del epitelio ciliado respiratorio, lo que impide el correcto deslizamiento del moco a través del árbol traqueobraquial, lo que conlleva al estancamiento del moco que servirá como cultivo para diversos microorganismos (Bradley y cols., 2015;Hoen y cols., 2015).…”

Computational Approaches to Study Microbes and Microbiomes

“…For example, a series of studies have characterized the microbiome in lungs of individuals with conditions such as cystic fibrosis (CF), 13–16 chronic obstructive pulmonary disease (COPD), 17 asthma, 3,18 and in the intestinal tract of individuals with CF 19 , and diabetes. 4,20 In some cases it has been possible to identify pathogens and/or the expression of particular genes that are associated with positive or negative outcomes.…”

“…4,20 In some cases it has been possible to identify pathogens and/or the expression of particular genes that are associated with positive or negative outcomes. 19,21 It is the hope that knowledge of the microbiome and gene expression can be leveraged to develop more targeted interventions and preventative treatments.…”

Deciphering the Lung Microbiome: Implications for Lung Health and Disease

“…Reduced diversity of the gut microbiome in early life correlates with the development of asthma [14] and outcomes in CF [15,16]. However, our understanding of the direct impact on the lung microbiome of dysbiosis in the gut is very immature.…”

“…The lung microbiome in patients with CF shows evidence of microbiome that is commonly found in the gut [16]. Furthermore, the patterns of the respiratory microbiome have been shown to correlate with breastfeeding, and disease progression, including timing of Pseudomonas colonization [15]. Madan et al [17] have begun to elucidate the interactions between these two communities and the potential effect of probiotics and other interventions on the gut, and subsequently, lung microbiome.…”