title: Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut.
abstract: BACKGROUND
  Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models.
  
  
  METHODS
  Tumor necrosis factor (TNF)-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells (IECs) was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR.
  
  
  RESULTS
  Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression.
  
  
  CONCLUSIONS
  The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human IECs and directly modulates IEC innate immune gene expression.
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: Kriston
authors.initials: K
authors.lastname: Ganguli
authors.affiliation: 1] Functional Foods Forum, University of Turku, Turku, Finland [2] Department of Biotechnology, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Collado
authors.affiliation: Institute of Dentistry, University of Turku, Turku, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Rautava
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: Lei
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Reetta
authors.initials: R
authors.lastname: Satokari
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Ingemar
authors.initials: I
authors.lastname: von Ossowski
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Justus
authors.initials: J
authors.lastname: Reunanen
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Airi
authors.initials: A
authors.lastname: Palva
authors.affiliation: Department of Paediatrics, University of Turku, Turku, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Isolauri
authors.affiliation: Functional Foods Forum, University of Turku, Turku, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Salminen
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
authors.forename: W Allan
authors.initials: WA
authors.lastname: Walker
authors.affiliation: Department of Paediatrics, University of Turku, Turku, Finland.
authors.forename: Samuli
authors.initials: S
authors.lastname: Rautava
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D010861:Fimbriae, Bacterial; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007082:Ileum / Q000196:embryology* / Q000382:microbiology*; D007150:Immunohistochemistry; D007249:Inflammation; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D019936:Probiotics; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012486:Salmonella typhimurium; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C508609:IL10 protein, human; C508590:IL1R1 protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D053573:Receptors, Interleukin-1 Type I; D011994:Recombinant Proteins; C104625:SpaC protein, bacteria; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10