title: Modulatory activity of Lactobacillus rhamnosus OLL2838 in a mouse model of intestinal immunopathology.
abstract: Gut microbiota and probiotic strains play an important role in oral tolerance by modulating regulatory and effector cell components of the immune system. We have previously described the ability of Lactobacilli to influence both the innate and adaptive immunity to wheat gluten, a food antigen, in mouse. In this study, we further explored the immunomodulatory mechanisms elicited in this model by testing three specific probiotic strains, namely L. rhamnosus OLL2838, B. infantis ATCC15697 and S. thermophilus Sfi39. In vitro analysis showed the all tested strains induced maturation of bone marrow derived dendritic cells (DCs). However, only L. rhamnosus induced appreciable levels of IL-10 and nitric oxide productions, whereas S. thermophilus essentially elicited IL-12 and TNF-α. The anti-inflammatory ability of OLL2838 was then tested in vivo by adopting mice that develop a gluten-specific enteropathy. This model is characterized by villus blunting, crypt hyperplasia, high levels of intestinal IFN-γ, increased cell apoptosis in lamina propria, and reduced intestinal total glutathione (GSHtot) and glutathione S-transferase (GST) activity. We found that, following administration of OLL2838, GSHtot and GST activity were enhanced, whereas caspase-3 activity was reduced. On the contrary, this probiotic strain failed in recovering the normal histology and further increased intestinal IFN-γ. Confocal microscopy revealed the inability of the probiotic strain to appropriately interact with enterocytes of the small intestine and with Peyer's patches in treated mice. In conclusion, these data highlighted the potential of L. rhamnosus OLL2838 to recover specific toxicity parameters induced by gluten in enteropathic mice through mechanisms that involve induction of low levels of reactive oxygen species (ROS).
authors.affiliation: National Agriculture and Food Research Organization, National Food Research Institute Food Function Division, Functional Food Factor Laboratory, Tsukuba, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Ogita
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bergamo
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maurano
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: D'Arienzo
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mazzarella
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bozzella
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy.
authors.forename: Diomira
authors.initials: D
authors.lastname: Luongo
authors.affiliation: Food Science Institute, Meiji Corp., Ltd., Odawara, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sashihara
authors.affiliation: Hiroshima University, Graduate School of Biosphere Science, Hiroshima, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Hiroshima University, Graduate School of Biosphere Science, Hiroshima, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy. Electronic address: mrossi@isa.cnr.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Rossi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D016130:Immunophenotyping; D007410:Intestinal Diseases / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D052201:Lacticaseibacillus rhamnosus / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009569:Nitric Oxide; D018384:Oxidative Stress; D019936:Probiotics
chemical_list: D015703:Antigens, CD; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen; D009569:Nitric Oxide
keywords: Enteropathy; Gluten; Immunomodulation; Lactobacilli; Transgenic mice