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Author (up) Dzidic, M.; Abrahamsson, T.R.; Artacho, A.; Bjorksten, B.; Collado, M.C.; Mira, A.; Jenmalm, M.C. file  url
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  Title Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development Type Journal Article
  Year 2017 Publication The Journal of Allergy and Clinical Immunology Abbreviated Journal J Allergy Clin Immunol  
  Volume 139 Issue 3 Pages 1017-1025.e14  
  Keywords Bacteria/isolation & purification; Bacterial Load; Child; Child, Preschool; Feces/*microbiology; Female; *Gastrointestinal Microbiome; Humans; Hypersensitivity/*immunology/*microbiology; Immunoglobulin A/*immunology; Infant; Male; Allergic disease; IgA index; IgA recognition patterns; asthma; childhood; gut microbiota; microbiome composition; secretory IgA  
  Abstract BACKGROUND: Although a reduced gut microbiota diversity and low mucosal total IgA levels in infancy have been associated with allergy development, IgA responses to the gut microbiota have not yet been studied. OBJECTIVE: We sought to determine the proportions of IgA coating together with the characterization of the dominant bacteria, bound to IgA or not, in infant stool samples in relation to allergy development. METHODS: A combination of flow cytometric cell sorting and deep sequencing of the 16S rDNA gene was used to characterize the bacterial recognition patterns by IgA in stool samples collected at 1 and 12 months of age from children staying healthy or having allergic symptoms up to 7 years of age. RESULTS: The children with allergic manifestations, particularly asthma, during childhood had a lower proportion of IgA bound to fecal bacteria at 12 months of age compared with healthy children. These alterations cannot be attributed to differences in IgA levels or bacterial load between the 2 groups. Moreover, the bacterial targets of early IgA responses (including coating of the Bacteroides genus), as well as IgA recognition patterns, differed between healthy children and children with allergic manifestations. Altered IgA recognition patterns in children with allergy were observed already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breast-fed children. CONCLUSION: An aberrant IgA responsiveness to the gut microbiota during infancy precedes asthma and allergy development, possibly indicating an impaired mucosal barrier function in allergic children.  
  Call Number Serial 1933  
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Author (up) Kepert, I.; Fonseca, J.; Muller, C.; Milger, K.; Hochwind, K.; Kostric, M.; Fedoseeva, M.; Ohnmacht, C.; Dehmel, S.; Nathan, P.; Bartel, S.; Eickelberg, O.; Schloter, M.; Hartmann, A.; Schmitt-Kopplin, P.; Krauss-Etschmann, S. file  url
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  Title D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease Type Journal Article
  Year 2017 Publication The Journal of Allergy and Clinical Immunology Abbreviated Journal J Allergy Clin Immunol  
  Volume 139 Issue 5 Pages 1525-1535  
  Keywords D-tryptophan; allergic airway disease; bacterial substance; gut microbiota; immune modulation; probiotic bacteria; screening  
  Abstract BACKGROUND: Chronic immune diseases, such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals, such as probiotics, for the prevention of allergic disease. However, clinical trials have produced inconsistent results. This is at least partly explained by the highly complex crosstalk among probiotic bacteria, the host's microbiota, and immune cells. The identification of a bioactive substance from probiotic bacteria could circumvent this difficulty. OBJECTIVE: We sought to identify and characterize a bioactive probiotic metabolite for potential prevention of allergic airway disease. METHODS: Probiotic supernatants were screened for their ability to concordantly decrease the constitutive CCL17 secretion of a human Hodgkin lymphoma cell line and prevent upregulation of costimulatory molecules of LPS-stimulated human dendritic cells. RESULTS: Supernatants from 13 of 37 tested probiotic strains showed immunoactivity. Bioassay-guided chromatographic fractionation of 2 supernatants according to polarity, followed by total ion chromatography and mass spectrometry, yielded C11H12N2O2 as the molecular formula of a bioactive substance. Proton nuclear magnetic resonance and enantiomeric separation identified D-tryptophan. In contrast, L-tryptophan and 11 other D-amino acids were inactive. Feeding D-tryptophan to mice before experimental asthma induction increased numbers of lung and gut regulatory T cells, decreased lung TH2 responses, and ameliorated allergic airway inflammation and hyperresponsiveness. Allergic airway inflammation reduced gut microbial diversity, which was increased by D-tryptophan. CONCLUSIONS: D-tryptophan is a newly identified product from probiotic bacteria. Our findings support the concept that defined bacterial products can be exploited in novel preventative strategies for chronic immune diseases.  
  Call Number Serial 1934  
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Author (up) Stiemsma, L.T.; Arrieta, M.-C.; Dimitriu, P.A.; Cheng, J.; Thorson, L.; Lefebvre, D.L.; Azad, M.B.; Subbarao, P.; Mandhane, P.; Becker, A.; Sears, M.R.; Kollmann, T.R.; Mohn, W.W.; Finlay, B.B.; Turvey, S.E. file  url
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  Title Shifts in Lachnospira and Clostridium sp. in the 3-month stool microbiome are associated with preschool age asthma Type Journal Article
  Year 2016 Publication Clinical Science (London, England : 1979) Abbreviated Journal Clin Sci (Lond)  
  Volume 130 Issue 23 Pages 2199-2207  
  Keywords atopic disease; dysbiosis; gut microbiota; hygiene hypothesis; microflora hypothesis  
  Abstract Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in 1-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n=39) or matched healthy controls (n=37). 16S rRNA sequencing and quantitative PCR (qPCR) were used to analyse the composition of the 3-month and 1-year gut microbiome of these children. At 3 months the abundance of the genus, Lachnospira (L), was decreased (P=0.008), whereas the abundance of the species, Clostridium neonatale (C), was increased (P=0.07) in asthmatics. Quartile analysis of stool composition at 3-months revealed a negative association between the ratio of these two bacteria (L/C) and asthma risk by 4 years of age [quartile 1: odds ratio (OR)=15, P=0.02, CI (confidence interval)= 1.8-124.7; quartile 2: OR=1.0, ns; quartile 3: OR=0.37, ns]. We conclude that opposing shifts in the relative abundances of Lachnospira and C. neonatale in the first 3 months of life are associated with preschool age asthma, and that the L/C ratio may serve as a potential early life biomarker to predict asthma development.  
  Call Number Serial 1931  
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