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      Airway microbiome composition correlates with lung function and arterial stiffness in an age-dependent manner

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          Abstract

          Objective

          To investigate age-associated changes in airway microbiome composition and their relationships with lung function and arterial stiffness among genetically matched young and elderly pairs.

          Methods

          Twenty-four genetically linked family pairs comprised of younger (≤40 years) and older (≥60 years) healthy participants were recruited (Total n = 48). Lung function and arterial stiffness (carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx)) were assessed. Sputum samples were collected for targeted 16S rRNA gene amplicon sequencing and correlations between microbiome composition, lung function and arterial stiffness were investigated.

          Results

          Elderly participants exhibited reductions in lung function (FEV1 ( p<0.001), FVC ( p<0.001) and percentage FEV1/FVC ( p = 0.003)) and a 1.3–3.9-fold increase in arterial stiffness ( p<0.001) relative to genetically related younger adults. Elderly adults had a higher relative abundance of Firmicutes ( p = 0.035) and lower relative abundance of Proteobacteria ( p = 0.014), including specific genera Haemophilus ( p = 0.024) and Lautropia ( p = 0.020) which were enriched in the younger adults. Alpha diversity was comparable between young and elderly pairs ( p>0.05) but was inversely associated with lung function (FEV1%Predicted and FVC %Predicted) in the young ( p = 0.006 and p = 0.003) though not the elderly ( p = 0.481 and p = 0.696). Conversely, alpha diversity was negatively associated with PWV in the elderly ( p = 0.01) but not the young ( p = 0.569). Specifically, phylum Firmicutes including the genus Gemella were correlated with lung function (FVC %Predicted) in the young group ( p = 0.047 and p = 0.040), while Fusobacteria and Leptotrichia were associated with arterial stiffness (PWV) in the elderly (both p = 0.004).

          Conclusion

          Ageing is associated with increased Firmicutes and decreased Proteobacteria representation in the airway microbiome among a healthy Asian cohort. The diversity and composition of the airway microbiome is independently associated with lung function and arterial stiffness in the young and elderly groups respectively. This suggests differential microbial associations with these phenotypes at specific stages of life with potential prognostic implications.

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          Most cited references30

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          Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians

          Background Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. Methodology/Principal Findings By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. Conclusions/Significance We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.
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            Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease.

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              Analysis of the Upper Respiratory Tract Microbiotas as the Source of the Lung and Gastric Microbiotas in Healthy Individuals

              ABSTRACT No studies have examined the relationships between bacterial communities along sites of the upper aerodigestive tract of an individual subject. Our objective was to perform an intrasubject and intersite analysis to determine the contributions of two upper mucosal sites (mouth and nose) as source communities for the bacterial microbiome of lower sites (lungs and stomach). Oral wash, bronchoalveolar lavage (BAL) fluid, nasal swab, and gastric aspirate samples were collected from 28 healthy subjects. Extensive analysis of controls and serial intrasubject BAL fluid samples demonstrated that sampling of the lungs by bronchoscopy was not confounded by oral microbiome contamination. By quantitative PCR, the oral cavity and stomach contained the highest bacterial signal levels and the nasal cavity and lungs contained much lower levels. Pyrosequencing of 16S rRNA gene amplicon libraries generated from these samples showed that the oral and gastric compartments had the greatest species richness, which was significantly greater in both than the richness measured in the lungs and nasal cavity. The bacterial communities of the lungs were significantly different from those of the mouth, nose, and stomach, while the greatest similarity was between the oral and gastric communities. However, the bacterial communities of healthy lungs shared significant membership with the mouth, but not the nose, and marked subject-subject variation was noted. In summary, microbial immigration from the oral cavity appears to be the significant source of the lung microbiome during health, but unlike the stomach, the lungs exhibit evidence of selective elimination of Prevotella bacteria derived from the upper airways.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Project administration
                Role: Project administration
                Role: Project administration
                Role: Project administration
                Role: ConceptualizationRole: Funding acquisitionRole: Supervision
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 November 2019
                2019
                : 14
                : 11
                : e0225636
                Affiliations
                [001]Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
                University of Alabama-Birmingham, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ Joint Senior Authors

                Author information
                http://orcid.org/0000-0003-0417-7607
                http://orcid.org/0000-0002-3863-0994
                Article
                PONE-D-19-22484
                10.1371/journal.pone.0225636
                6879132
                31770392
                071ebdd5-c647-4cdc-9221-5086d0b0fd02
                © 2019 Lee et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 August 2019
                : 16 October 2019
                Page count
                Figures: 5, Tables: 2, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001475, Nanyang Technological University;
                Award ID: ARISE/2017/6
                Award Recipient :
                This work received a grant award by Ageing Research Institute for Society and Education (ARISE), Nanyang Technological University, Singapore, ARISE/2017/6 ( http://arise.ntu.edu.sg) to SHC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbiome
                Biology and Life Sciences
                Genetics
                Genomics
                Microbial Genomics
                Microbiome
                Biology and Life Sciences
                Microbiology
                Microbial Genomics
                Microbiome
                People and Places
                Population Groupings
                Age Groups
                Elderly
                Medicine and Health Sciences
                Pulmonology
                Pulmonary Function
                Physical Sciences
                Materials Science
                Material Properties
                Mechanical Properties
                Stiffness
                Medicine and Health Sciences
                Geriatrics
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Mucus
                Sputum
                Biology and Life Sciences
                Physiology
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Mucus
                Sputum
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Saliva
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Saliva
                Biology and Life Sciences
                Physiology
                Body Fluids
                Saliva
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Saliva
                Biology and Life Sciences
                Developmental Biology
                Organism Development
                Aging
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Aging
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Aging
                Custom metadata
                All microbiome sequencing data files are available from the SRA database (accession number PRJNA559069).

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