title: Dietary pectin-derived acidic oligosaccharides improve the pulmonary bacterial clearance of Pseudomonas aeruginosa lung infection in mice by modulating intestinal microbiota and immunity.
abstract: BACKGROUND
  A predominantly T-helper type 2 (Th2) immune response is critical in the prognosis of pulmonary Pseudomonas aeruginosa infection. But the mucosal and systemic immune responses can be influenced by the intestinal microbiota.
  
  
  METHODS
  We assessed the effect of microbiota compositional changes induced by a diet enriched in 5% acidic oligosaccharides derived from pectin (pAOS) on the immune response and outcome of chronic pulmonary P. aeruginosa infection in mice.
  
  
  RESULTS
  pAOS promoted Th1 polarization by increasing interferon γ release, upregulating t-bet gene expression, decreasing interleukin 4 secretion, and downregulating gata3 gene expression. pAOS also sustained the release of keratinocyte chemoattractant, recruited polynuclear leukocytes and macrophages, stimulated M1 macrophage activation and interleukin 10 release, and decreased tumor necrosis factor α release in the lung. These effects led to increased bacterial clearance after the first and second P. aeruginosa infections. pAOS modified the intestinal microbiota by stimulating the growth of species involved in immunity development, such as Bifidobacterium species, Sutturella wadsworthia, and Clostridium cluster XIVa organisms, and at the same time increased the production of butyrate and propionate.
  
  
  CONCLUSIONS
  These results suggest that pAOS may have beneficial effects by limiting the number and severity of pulmonary exacerbations in patients chronically infected with P. aeruginosa, such as individuals with cystic fibrosis.
authors.affiliation: Unité INSERM 995, Faculté de médecine, Université Lille 2, France.
authors.forename: Henry
authors.initials: H
authors.lastname: Bernard
authors.affiliation: Unité INSERM 995, Faculté de médecine, Université Lille 2, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Desseyn
authors.affiliation: Nutricia Research, Utrecht.
authors.forename: Nana
authors.initials: N
authors.lastname: Bartke
authors.affiliation: Laboratory of Microbiology, Wageningen University, The Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: Kleinjans
authors.affiliation: Nutricia Research, Utrecht.
authors.forename: Bernd
authors.initials: B
authors.lastname: Stahl
authors.affiliation: Laboratory of Microbiology, Wageningen University, The Netherlands.
authors.forename: Clara
authors.initials: C
authors.lastname: Belzer
authors.affiliation: Nutricia Research, Utrecht Laboratory of Microbiology, Wageningen University, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Knol
authors.affiliation: Unité INSERM 995, Faculté de médecine, Université Lille 2, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gottrand
authors.affiliation: Unité INSERM 995, Faculté de médecine, Université Lille 2, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Husson
mesh_terms: D000818:Animals; D002630:Chemotactic Factors / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology*; D015603:Keratinocytes / Q000276:immunology / Q000382:microbiology; D007962:Leukocytes / Q000276:immunology / Q000382:microbiology; D008171:Lung Diseases / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D064307:Microbiota / Q000187:drug effects* / Q000276:immunology; D009844:Oligosaccharides / Q000494:pharmacology*; D010368:Pectins / Q000737:chemistry*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D020825:T-Box Domain Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D002630:Chemotactic Factors; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C556062:IL10 protein, mouse; D009844:Oligosaccharides; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D010368:Pectins
keywords: P. aeruginosa lung infection; Th1 and M1 polarization; intestinal microbiota; prebiotics