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ORIGINAL RESEARCH ARTICLE

Bifidobacterium breve and Streptococcus thermophilus Secretion Products Enhance T Helper 1 Immune Response and Intestinal Barrier in Mice

Sandrine Ménard^*, David Laharie, Corinne Asensio, Teresita Vidal-Martinez^*, Céline Candalh^*, Anne Rullier, Frank Zerbib, Francis Mégraud, Tamara Matysiak-Budnik^* and Martine Heyman^*,1

^* INSERM EMI 0212, Faculté Cochin-Necker, Paris, France; Laboratoire de Bactériologie, Université Victor Segalen Bordeaux II, Bordeaux, France; and Service d’Anatomo-Pathologie, Hopital Pellegrin, Bordeaux, France

To whom requests for reprints should be addressed at ¹ INSERM EMI 0212, Faculté Cochin Necker, 156 rue de Vaugirard, 75730 Paris, France. E-mail: heyman{at}necker.fr

Lactic acid bacteria or their secretion products can modulate immune responses differently in normal and inflammatory conditions. This comparative study analyzes the effect of oral administration of living lactic acid bacteria, or their conditioned media, on the epithelial and immune functions of colitis-prone C57BL/6 IL-10-deficient mice. Mice were untreated (control) or infected with Helicobacter hepaticus with or without oral treatment with living bacteria, Bifidobacterium breve C50 and Streptococcus thermophilus 065 (LB), or their culture-conditioned media (CM). Histology, cytokine mRNA, electrical resistance, and barrier capacity of colonic samples as well as cytokine secretion by mesenteric lymph node (MLN) cells were studied. Helicobacter hepaticus mice developed only mild colitis, which was not modified in LB or CM groups. In the CM (but not the LB) group, the colonic barrier was reinforced as compared to the other groups, as evidenced by decreased horseradish peroxidase (HRP) transcytosis and mannitol fluxes and increased electrical resistance. In MLN, the percentage of CD4⁺ and CD8⁺ T cells secreting IFN was significantly higher in CM (2.06% and 1.98%, respectively) mice than in H. hepaticus (1.1% and 0.47%, P < 0.05) or control mice. In addition, the nonspecific stimulation of IFN, TNF, and IL-12 secretion by MLN cells was significantly higher in the CM group as compared to the other groups. In the absence of severe colitis, Bifidobacterium breve C50- and Streptococcus thermophilus 065-conditioned media can reinforce intestinal barrier capacity and stimulate Th1 immune response, highlighting the involvement of lactic acid bacteria–derived components in host defense.

Key Words: probiotics • adjuvants • mucosal immunity • intestinal function