title: Environmentally determined differences in the murine lung microbiota and their relation to alveolar architecture.
abstract: Commensal bacteria control the micro-ecology of metazoan epithelial surfaces with pivotal effect on tissue homeostasis and host defense. In contrast to the upper respiratory tract, the lower respiratory tract of healthy individuals has largely been considered free of microorganisms. To understand airway micro-ecology we studied microbiota of sterilely excised lungs from mice of different origin including outbred wild mice caught in the natural environment or kept under non-specific-pathogen-free (SPF) conditions as well as inbred mice maintained in non-SPF, SPF or germ-free (GF) facilities. High-throughput pyrosequencing of reverse transcribed 16S rRNA revealed metabolically active murine lung microbiota in all but GF mice. The overall composition across samples was similar at the phylum and family level. However, species richness was significantly different between lung microbiota from SPF and non-SPF mice. Non-cultivatable Betaproteobacteria such as Ralstonia spp. made up the major constituents and were also confirmed by 16S rRNA gene cloning analysis. Additionally, Pasteurellaceae, Enterobacteria and Firmicutes were isolated from lungs of non-SPF mice. Bacterial communities were detectable by fluorescent in situ hybridization (FISH) at alveolar epithelia in the absence of inflammation. Notably, higher bacterial abundance in non-SPF mice correlated with more and smaller size alveolae, which was corroborated by transplanting Lactobacillus spp. lung isolates into GF mice. Our data indicate a common microbial composition of murine lungs, which is diversified through different environmental conditions and affects lung architecture. Identification of the microbiota of murine lungs will pave the path to study their influence on pulmonary immunity to infection and allergens using mouse models.
authors.affiliation: Research Center Borstel, Cellular Microbiology Group, Department of Molecular Infection Biology, Borstel, Germany.
authors.forename: Yeojun
authors.initials: Y
authors.lastname: Yun
authors.affiliation: MPI for Evolutionary Biology, Plön, Germany; Department of Dermatology, University of Lübeck, Lübeck, Germany.
authors.forename: Girish
authors.initials: G
authors.lastname: Srinivas
authors.affiliation: MPI for Evolutionary Biology, Plön, Germany; Evolutionary Genomics, Institute for Experimental Medicine, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Kuenzel
authors.affiliation: MPI for Evolutionary Biology, Plön, Germany; Evolutionary Genomics, Institute for Experimental Medicine, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Linnenbrink
authors.affiliation: Institute for Medical Microbiology and Hospital Hygiene, Philipps University Marburg, Marburg, Germany.
authors.forename: Safa
authors.initials: S
authors.lastname: Alnahas
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London, United Kingdom.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bruce
authors.affiliation: Institute for Medical Microbiology and Hospital Hygiene, Philipps University Marburg, Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steinhoff
authors.affiliation: MPI for Evolutionary Biology, Plön, Germany; Evolutionary Genomics, Institute for Experimental Medicine, Christian-Albrechts-University, Kiel, Germany.
authors.forename: John F
authors.initials: JF
authors.lastname: Baines
authors.affiliation: Research Center Borstel, Cellular Microbiology Group, Department of Molecular Infection Biology, Borstel, Germany.
authors.forename: Ulrich E
authors.initials: UE
authors.lastname: Schaible
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification* / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D008168:Lung / Q000033:anatomy & histology / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D008969:Molecular Sequence Data; D010802:Phylogeny; D011650:Pulmonary Alveoli / Q000033:anatomy & histology* / Q000382:microbiology* / Q000502:physiology; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D017423:Sequence Analysis, RNA; D013047:Specific Pathogen-Free Organisms
chemical_list: D012336:RNA, Ribosomal, 16S