title: Conditioned medium from Bifidobacteria infantis protects against Cronobacter sakazakii-induced intestinal inflammation in newborn mice.
abstract: Necrotizing enterocolitis (NEC) is associated with a high morbidity and mortality in very low birth weight infants. Several hypotheses regarding the pathogenesis of NEC have been proposed but to date no effective treatment is available. Previous studies suggest that probiotic supplementation is protective. We recently reported that probiotic (Bifidobacterium infantis) conditioned medium (PCM) has an anti-inflammatory effect in cultured fetal human intestinal cells (H4) and fetal intestine explants. In this study, we tested in vivo whether PCM protects neonatal mice from developing intestinal inflammation induced by exposure to Cronobacter sakazakii (C. sakazakii), an opportunistic pathogen associated with NEC. We found that infected neonatal mice had a significantly lower body weight than control groups. Infection led to ileal tissue damage including villous rupture, disruption of epithelial cell alignment, intestinal inflammation, apoptotic cell loss, and decreased mucus production. Pretreatment with PCM prevented infection caused decrease in body weight, attenuated enterocyte apoptotic cell death, mitigated reduced mucin production, and maintained ileal structure. Infected ileum expressed reduced levels of IκBα, which could be restored upon pretreatment with PCM. We also observed a nuclear translocation of NF-κB p65 in H4 cells exposed to C. sakazakii, which was prevented in PCM-pretreated cells. Finally, treatment of neonatal mice with PCM prior to infection sustained the capacity of ileal epithelial proliferation. This study suggests that an active component(s) released into the culture medium by B. infantis may prevent ileal damage by a pathogen linked to NEC.
authors.affiliation: Mucosal Immunology and Biology Research Center, Division of Pediatric Gastroenterology, Harvard Medical School, Boston, Massachusetts; and Mass General Hospital for Children, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
authors.forename: Meiqian
authors.initials: M
authors.lastname: Weng
authors.forename: Kriston
authors.initials: K
authors.lastname: Ganguli
authors.forename: Weishu
authors.initials: W
authors.lastname: Zhu
authors.forename: Hai Ning
authors.initials: HN
authors.lastname: Shi
authors.forename: W Allan
authors.initials: WA
authors.lastname: Walker
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001644:Bifidobacterium / Q000145:classification / Q000378:metabolism*; D001835:Body Weight; D002460:Cell Line; D049109:Cell Proliferation; D044083:Cronobacter sakazakii / Q000472:pathogenicity*; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D020895:Enterocytes / Q000382:microbiology / Q000473:pathology; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007079:Ileitis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D007082:Ileum / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D019936:Probiotics / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D020672:I-kappa B Proteins; D009077:Mucins; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha
keywords: Bifidobacterium infantis; Cronobacter sakazakii; necrotizing enterocolitis; neonatal intestinal inflammation; probiotic-conditioned media