Serial Analysis of the Gut and Respiratory Microbiome in Cystic Fibrosis in Infancy: Interaction between Intestinal and Respiratory Tracts and Impact of Nutritional Exposures

ABSTRACT Pulmonary damage caused by chronic colonization of the cystic fibrosis (CF) lung by microbial communities is the proximal cause of respiratory failure. While there has been an effort to document the microbiome of the CF lung in pediatric and adult patients, little is known regarding the developing microflora in infants. We examined the respiratory and intestinal microbiota development in infants with CF from birth to 21 months. Distinct genera dominated in the gut compared to those in the respiratory tract, yet some bacteria overlapped, demonstrating a core microbiota dominated by Veillonella and Streptococcus. Bacterial diversity increased significantly over time, with evidence of more rapidly acquired diversity in the respiratory tract. There was a high degree of concordance between the bacteria that were increasing or decreasing over time in both compartments; in particular, a significant proportion (14/16 genera) increasing in the gut were also increasing in the respiratory tract. For 7 genera, gut colonization presages their appearance in the respiratory tract. Clustering analysis of respiratory samples indicated profiles of bacteria associated with breast-feeding, and for gut samples, introduction of solid foods even after adjustment for the time at which the sample was collected. Furthermore, changes in diet also result in altered respiratory microflora, suggesting a link between nutrition and development of microbial communities in the respiratory tract. Our findings suggest that nutritional factors and gut colonization patterns are determinants of the microbial development of respiratory tract microbiota in infants with CF and present opportunities for early intervention in CF with altered dietary or probiotic strategies. IMPORTANCE While efforts have been focused on assessing the microbiome of pediatric and adult cystic fibrosis (CF) patients to understand how chronic colonization by these microbes contributes to pulmonary damage, little is known regarding the earliest development of respiratory and gut microflora in infants with CF. Our findings suggest that colonization of the respiratory tract by microbes is presaged by colonization of the gut and demonstrated a role of nutrition in development of the respiratory microflora. Thus, targeted dietary or probiotic strategies may be an effective means to change the course of the colonization of the CF lung and thereby improve patient outcomes.

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Complete genome sequence of sequential Pandoraea apista isolates from the same cystic fibrosis patient supports a model of chronic colonization with in vivo strain evolution over time

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2016.10.013 ◽

2017 ◽

Vol 87 (1) ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Alexander L. Greninger ◽

Jessica Streithorst ◽

Jeffrey A. Golden ◽

Charles Y. Chiu ◽

Steve Miller

Keyword(s):

Cystic Fibrosis ◽

Cystic Fibrosis Patient ◽

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Strain Evolution ◽

Chronic Colonization ◽

Over Time

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Intrinsic Carbapenem-Hydrolyzing Oxacillinases from Members of the Genus Pandoraea

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01112-15 ◽

2015 ◽

Vol 59 (11) ◽

pp. 7136-7141 ◽

Cited By ~ 6

Author(s):

Ines Schneider ◽

Adolf Bauernfeind

Keyword(s):

Escherichia Coli ◽

Cystic Fibrosis ◽

Respiratory Tract ◽

Host Strain ◽

Correct Identification ◽

Content Type ◽

Hydrolyzing Enzymes ◽

High Degree

ABSTRACTWe analyzed the oxacillinases of isolates of six different species ofPandoraea, a genus that colonizes the respiratory tract of cystic fibrosis patients. The isolates produced carbapenem-hydrolyzing enzymes causing elevated MICs for amoxicillin, piperacillin, meropenem, and imipenem when expressed in anEscherichia colihost strain. Sequencing revealed nine new oxacillinases (OXA-151 to OXA-159) with a high degree of identity among isolates of the same species; however, they had much lower interspecies similarities. The intrinsic oxacillinase genes might therefore be helpful for correct identification ofPandoraeaisolates.

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Evaluation of the Respiratory Microbiome and the Use of Tracheal Lavage as a Diagnostic Tool in Kemp’s Ridley Sea Turtles (Lepidochelys kempii)

Animals ◽

10.3390/ani11102927 ◽

2021 ◽

Vol 11 (10) ◽

pp. 2927

Author(s):

Kerry L. McNally ◽

Jennifer L. Bowen ◽

Jennifer O. Brisson ◽

Adam Kennedy ◽

Charles J. Innis

Keyword(s):

Microbial Community ◽

Respiratory Tract ◽

Microbial Communities ◽

Sea Turtles ◽

Sea Turtle ◽

Lepidochelys Kempii ◽

Kemp's Ridley Sea Turtles ◽

Tracheal Lavage ◽

High Degree ◽

Kemp's Ridley

Respiratory disease is a common cause of morbidity and mortality in sea turtles, including the Kemp’s ridley sea turtle (Lepidochelys kempii). Although culture-dependent methods are typically used to characterize microbes associated with pneumonia and to determine treatment, culture-independent methods can provide a deeper understanding of the respiratory microbial communities and lead to a more accurate diagnosis. In this study, we characterized the tracheal lavage microbiome from cold-stunned Kemp’s ridley sea turtles at three time points during rehabilitation (intake, rehabilitation, and convalescence) by analyzing the 16S rRNA gene collected from tracheal lavage samples. We retrospectively developed a radiographic scoring system to grade the severity of lung abnormalities in these turtles and found no differences in diversity or composition of microbial communities based on radiographic score. We also found that the culture isolates from tracheal lavage samples, as well as other previously reported sea turtle pathogens, were present in variable abundance across sequenced samples. In addition to the tracheal microbial community of live turtles, we characterized microbial communities from other segments of the respiratory tract (glottis, trachea, anterior lung, posterior lung) from deceased turtles. We found a high degree of variability within turtles and a high degree of dissimilarity between different segments of the respiratory tract and the tracheal lavage collected from the same turtle. In summary, we found that the pulmonary microbial community associated with pneumonia in sea turtles is complex and does not correlate well with the microbial community as identified by tracheal lavage. These results underscore the limitations of using tracheal lavage for identification of the causative agents of pneumonia in sea turtles.

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Respiratory tract microbiocenosis in children with cystic fibrosis in Kharkiv region

SOVREMENNAYA PEDIATRIYA ◽

10.15574/sp.2016.78.24 ◽

2016 ◽

Vol 78 (6) ◽

pp. 24-26

Author(s):

V.A. Klymenko ◽

◽

Y.A. Yanovskaya ◽

Y.V. Pasichnik ◽

◽

...

Keyword(s):

Cystic Fibrosis ◽

Respiratory Tract

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Stability and Fluctuation of Personality Disorder Features in Daily Life

10.31234/osf.io/tf5sc ◽

2018 ◽

Author(s):

Aidan G.C. Wright ◽

Leonard Simms

Keyword(s):

Personality Disorder ◽

Daily Life ◽

Daily Diary ◽

Personality Pathology ◽

Dynamic Processes ◽

Diary Study ◽

Daily Diary Study ◽

Symptom Exacerbation ◽

High Degree ◽

Over Time

Very little is known about the daily stability and fluctuation of personality pathology. To address this gap in knowledge, we investigated the naturalistic manifestation of personality pathology over the course of 100 days. A group of individuals (N=101) diagnosed with any personality disorder (PD) completed a daily diary study over 100 consecutive days (Mdn = 94 days, Range = 33-101 days). Participants completed daily ratings of 30 manifestations of personality pathology. Patterns of stability and variability over the course of the study were then examined. Results indicated that individual PD manifestations and domains of PD manifestations were variable across days and differed widely in their frequency. Additionally, individual averages and level of variability in PD domains were highly stable across months, individual averages of PD domains were predicted by baseline dispositional ratings of PD traits with a high degree of specificity, and daily variability PD domains was associated with elevated levels of PD traits. This pattern of findings suggests that dynamic processes of symptom exacerbation and diminution that are stable in mean level and variability in expression over time characterizes personality pathology. Further, dispositional ratings are significant predictors of average daily expression of PD features.

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Preliminary Report of In vitro and In vivo Effectiveness of Dornase Alfa on SARS-CoV-2 Infection (Preprint)

10.2196/preprints.20200 ◽

2020 ◽

Author(s):

Hacer Kuzu Okur ◽

Koray Yalcin ◽

Cihan Tastan ◽

Sevda Demir ◽

Bulut Yurtsever ◽

...

Keyword(s):

Cystic Fibrosis ◽

Respiratory Tract ◽

Mononuclear Cells ◽

Multiple Organ ◽

Peripheral Blood Mononuclear ◽

Dornase Alfa ◽

Tract Infections ◽

Adult Peripheral Blood

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.

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Microbial Communities in Full-Scale Wastewater Treatment Systems Exhibit Deterministic Assembly Processes and Functional Dependency over Time

Environmental Science & Technology ◽

10.1021/acs.est.0c06732 ◽

2021 ◽

Vol 55 (8) ◽

pp. 5312-5323

Author(s):

Jinjin Yu ◽

Siang Nee Tang ◽

Patrick K. H. Lee

Keyword(s):

Wastewater Treatment ◽

Microbial Communities ◽

Full Scale ◽

Functional Dependency ◽

Wastewater Treatment Systems ◽

Over Time

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Heritability of Longitudinal Measures of Body Mass Index and Lipid and Lipoprotein Levels in Aging Twins

Twin Research and Human Genetics ◽

10.1375/twin.10.5.703 ◽

2007 ◽

Vol 10 (5) ◽

pp. 703-711 ◽

Cited By ~ 52

Author(s):

Ellen L. Goode ◽

Stacey S. Cherny ◽

Joe C. Christian ◽

Gail P. Jarvik ◽

Mariza de Andrade

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Genetic Factors ◽

Significant Proportion ◽

Lipoprotein Cholesterol ◽

Equation Modeling ◽

Shared Environment ◽

Significant Contributor ◽

Age Related ◽

Over Time

AbstractBody-mass index (BMI), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels are known to be highly heritable. We evaluated the genetic and environmental relationships of these measures over time in an analysis of twin pairs. Monozygotic (235 pairs) and dizygotic (260 pairs) male twins were participants in the National Heart Lung and Blood Institute Veteran Twin Study, and were followed with three clinical exams from mean age 48 years to mean age 63 years. Structural equation modeling (SEM) with adjustment forAPOEgenotype (a significant contributor to TC and LDL-C) was used to assess longitudinal patterns of heritability. Results indicated a contribution of genetic factors to BMI, TC, LDL-C, HLD-C, and TG. Modest increases over time were observed in the heritability of BMI (from 0.48 to 0.61), TC (from 0.46 to 0.57), LDL-C (from 0.49 to 0.64), and HDL-C (from 0.50 to 0.62), but this trend was not present for TG. There was a corresponding decrease in shared environmental influences over time for these traits, although shared environment was a significant contributor only for HDL-C. Moreover, we observed that genetic influences for all measures were significantly correlated over time, and we found no evidence of age-specific genetic effects. In summary, longitudinal analyses of twin data indicate that genetic factors do not account for a significant proportion of the variation in age-related changes of BMI or lipid and lipoprotein levels.

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