title: Pectin-Derived Acidic Oligosaccharides Improve the Outcome of Pseudomonas aeruginosa Lung Infection in C57BL/6 Mice.
abstract: The administration of prebiotics as oligosaccharides (OS), by acting on intestinal microbiota, could modulate the immune and inflammatory response and represent a new strategy to improve the outcome of bacterial infection. The aim of this study was to determine whether pectin-derived acidic oligosaccharides (pAOS) could modulate the outcome of pulmonary P. aeruginosa (PA) infection in C57BL/6 mice, which develop a Th1 response to PA lung infection. Mice were randomized for 5 weeks to consume a control or a 5% pAOS diet and chronically infected by PA. Resistance to a second PA infection was also analyzed by reinfecting the surviving mice 2 weeks after the first infection. Compared with control mice, mice fed pAOS had reduced mortality (P<0.05). This improvement correlated with a better control of the inflammatory response with a lower neutrophil count on day 1 (P<0.05), a sustained neutrophil and macrophage recruitment on days 2 and 3 (P<0.01) a greater and sustained IL-10 release in lung (P<0.05) and a reduction of the Th1 response and M1 activation with a lower IFN-γ/IL-4 (P<0.01) and nos2/arg1 (P<0.05) ratios. These results coincided with a modulation of the intestinal microbiota as shown by an increased butyric acid concentration in feces (P<0.05). Moreover, pAOS decreased the bacterial load (P<0.01) in mice reinfected 2 weeks after the first infection, suggesting that pAOS could reduce pulmonary exacerbations. In conclusion, pAOS improved the outcome of PA infection in C57BL/6 mice by modulating the intestinal microbiota and the inflammatory and immune responses.
authors.affiliation: LIRIC UMR 995 Inserm; Université de Lille; CHRU de Lille, Faculté de Médecine, Place de Verdun, F-59045, Lille cedex, France.
authors.forename: Henry
authors.initials: H
authors.lastname: Bernard
authors.affiliation: LIRIC UMR 995 Inserm; Université de Lille; CHRU de Lille, Faculté de Médecine, Place de Verdun, F-59045, Lille cedex, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Desseyn
authors.affiliation: LIRIC UMR 995 Inserm; Université de Lille; CHRU de Lille, Faculté de Médecine, Place de Verdun, F-59045, Lille cedex, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gottrand
authors.affiliation: Nutricia Research, Uppsalalaan 12, 3584 CT Utrecht, The Netherlands.
authors.forename: Bernd
authors.initials: B
authors.lastname: Stahl
authors.affiliation: Nutricia Research, Uppsalalaan 12, 3584 CT Utrecht, The Netherlands.
authors.forename: Nana
authors.initials: N
authors.lastname: Bartke
authors.affiliation: LIRIC UMR 995 Inserm; Université de Lille; CHRU de Lille, Faculté de Médecine, Place de Verdun, F-59045, Lille cedex, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Husson
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000276:immunology; D004032:Diet; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D008171:Lung Diseases / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000627:therapeutic use*; D010368:Pectins / Q000737:chemistry*; D011014:Pneumonia / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology*; D011550:Pseudomonas aeruginosa; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005232:Fatty Acids, Volatile; D009844:Oligosaccharides; D010368:Pectins