Previous studies indicate that certain probiotic bacterial strains or their soluble products can alleviate proinflammatory cytokine secretion by intestinal epithelial cells (IEC), but their impact on epithelial chloride (Cl−) secretion remains elusive. To further decipher the mechanisms of the cross-talk between bacteria/soluble factors and epithelial cells, we analyzed the capacity of the probiotic strain Bifidobacterium breve C50 (Bb C50), its conditioned medium, and other commensal Gram (+) bacteria to modulate epithelial Cl− secretion. The effect of Bb C50 on carbachol- (CCh) or forskolin (Fsk)-induced Cl− secretion was measured in an IEC line in Ussing chambers. The mechanisms involved in the regulation of Cl− secretion were assessed by measuring intracellular Ca2+ concentration, phosphatase activity, protein kinase (PK) C and PKA activation, and cystic fibrosis transmembrane conductance regulator (CFTR) expression. CCh- or Fsk-induced Cl− secretion [short-circuit current (Isc): 151 ± 28 and 98 ± 14 μA/cm2, respectively] was inhibited dose-dependently by Bb C50 (Isc 33 ± 12 and 49 ± 7 μA/cm2 at multiplicity of infection 100; P < 0.02). Fsk-induced Cl− secretion was also inhibited by Lactobacillus rhamnosus 10893. No other inhibitory effect was recorded with the other Gram (+) bacteria tested. The inhibitory effect of Bb C50 on CCh-induced Cl− secretion targeted a step downstream of epithelial Ca2+ mobilization and was associated with decreased PKC activity. Thus, Bb C50 and secreted soluble factors, by inhibiting phosphorylation processes, may promote intestinal homeostasis by controlling Cl− secretion.
Supported by the French Ministry of Research and Education, Bledina-SA, the Princess Grace de Monaco foundation, INSERM, and the “Fondation pour la Recherche Médicale.”
