title: Early administration of probiotic Lactobacillus acidophilus and/or prebiotic inulin attenuates pathogen-mediated intestinal inflammation and Smad 7 cell signaling.
abstract: Immaturity of gut-associated immunity may contribute to pediatric mortality associated with enteric infections. A murine model to parallel infantile enteric disease was used to determine the effects of probiotic, Lactobacillus acidophilus (La), prebiotic, inulin, or both (synbiotic, syn) on pathogen-induced inflammatory responses, NF-κB, and Smad 7 signaling. Newborn mice were inoculated bi-weekly for 4 weeks with La, inulin, or syn and challenged with Citrobacter rodentium (Cr) at 5 weeks. Mouse intestinal epithelial cells (CMT93) were exposed to Cr to determine temporal alterations in NF-Kappa B and Smad 7 levels. Mice with pretreatment of La, inulin, and syn show reduced intestinal inflammation following Cr infection compared with controls, which is associated with significantly reduced bacterial colonization in La, inulin, and syn animals. Our results further show that host defense against Cr infection correlated with enhanced colonic IL-10 and transforming growth factor-β expression and inhibition of NF-κB in syn-treated mice, whereas mice pretreated with syn, La, or inulin had attenuation of Cr-induced Smad 7 expression. There was a temporal Smad 7 and NF-κB intracellular accumulation post-Cr infection and post-tumor necrosis factor stimulation in CMT93 cells. These results, therefore, suggest that probiotic, La, prebiotic inulin, or synbiotic may promote host-protective immunity and attenuate Cr-induced intestinal inflammation through mechanisms affecting NF-κB and Smad 7 signaling.
authors.affiliation: Mucosal Immunology Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: Ondulla T
authors.initials: OT
authors.lastname: Foye
authors.forename: I-Fei
authors.initials: IF
authors.lastname: Huang
authors.forename: Christine C
authors.initials: CC
authors.lastname: Chiou
authors.forename: W Allan
authors.initials: WA
authors.lastname: Walker
authors.forename: Hai Ning
authors.initials: HN
authors.lastname: Shi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D044082:Citrobacter rodentium / Q000276:immunology / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D005759:Gastroenteritis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D007444:Inulin / Q000008:administration & dosage*; D007779:Lactobacillus acidophilus / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D056692:Prebiotics / Q000382:microbiology*; D019936:Probiotics / Q000008:administration & dosage*; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: D016328:NF-kappa B; D056692:Prebiotics; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007444:Inulin