title: Alterations of lung microbiota in a mouse model of LPS-induced lung injury.
abstract: Acute lung injury (ALI) and the more severe acute respiratory distress syndrome are common responses to a variety of infectious and noninfectious insults. We used a mouse model of ALI induced by intratracheal administration of sterile bacterial wall lipopolysaccharide (LPS) to investigate the changes in innate lung microbiota and study microbial community reaction to lung inflammation and barrier dysfunction induced by endotoxin insult. One group of C57BL/6J mice received LPS via intratracheal injection (n = 6), and another received sterile water (n = 7). Bronchoalveolar lavage (BAL) was performed at 72 h after treatment. Bacterial DNA was extracted and used for qPCR and 16S rRNA gene-tag (V3-V4) sequencing (Illumina). The bacterial load in BAL from ALI mice was increased fivefold (P = 0.03). The community complexity remained unchanged (Simpson index, P = 0.7); the Shannon diversity index indicated the increase of community evenness in response to ALI (P = 0.07). Principal coordinate analysis and analysis of similarity (ANOSIM) test (P = 0.005) revealed a significant difference between microbiota of control and ALI groups. Bacteria from families Xanthomonadaceae and Brucellaceae increased their abundance in the ALI group as determined by Metastats test (P < 0.02). In concordance with the 16s-tag data, Stenotrohomonas maltophilia (Xanthomonadaceae) and Ochrobactrum anthropi (Brucellaceae) were isolated from lungs of mice from both groups. Metabolic profiling of BAL detected the presence of bacterial substrates suitable for both isolates. Additionally, microbiota from LPS-treated mice intensified IL-6-induced lung inflammation in naive mice. We conclude that the morbid transformation of ALI microbiota was attributed to the set of inborn opportunistic pathogens thriving in the environment of inflamed lung, rather than the external infectious agents.
authors.affiliation: Department of Pediatrics, The University of Chicago, Chicago, Illinois; poroyko@uchicago.edu.
authors.forename: Valeriy
authors.initials: V
authors.lastname: Poroyko
authors.affiliation: Section of Pulmonary and Critical Medicine, Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, Illinois;
authors.forename: Fanyong
authors.initials: F
authors.lastname: Meng
authors.affiliation: Section of Pulmonary and Critical Medicine, Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, Illinois;
authors.forename: Angelo
authors.initials: A
authors.lastname: Meliton
authors.affiliation: Section of Pulmonary and Critical Medicine, Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, Illinois;
authors.forename: Taras
authors.initials: T
authors.lastname: Afonyushkin
authors.affiliation: Roy J. Carver Biotechnology Center, University of Illinois at Urbana-Champaign;
authors.forename: Alexander
authors.initials: A
authors.lastname: Ulanov
authors.affiliation: Department of Microbiology and Immunology, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois;
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Semenyuk
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, Illinois; and.
authors.forename: Omar
authors.initials: O
authors.lastname: Latif
authors.affiliation: Department of Pathology, University of Chicago, Chicago, Illinois.
authors.forename: Vera
authors.initials: V
authors.lastname: Tesic
authors.affiliation: Section of Pulmonary and Critical Medicine, Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, Illinois;
authors.forename: Anna A
authors.initials: AA
authors.lastname: Birukova
authors.affiliation: Section of Pulmonary and Critical Medicine, Lung Injury Center, Department of Medicine, The University of Chicago, Chicago, Illinois;
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Birukov
mesh_terms: D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D042021:Brucellaceae / Q000235:genetics / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000382:microbiology*; D055370:Lung Injury / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D044166:Xanthomonadaceae / Q000235:genetics / Q000302:isolation & purification
chemical_list: D004269:DNA, Bacterial; D008070:Lipopolysaccharides; D012336:RNA, Ribosomal, 16S
keywords: LPS; acute lung injury; metabolic profiling; microbiota