Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity

VINDEROLA, G.; MATAR, C.; PERDIGON, G.

BMC Immunology

BioMed Central

Año: 2007 p. 8 - 19

Background: Fermented milks containing probiotic bacteria are a way of delivering bioactiveconstituents to targets in the gastrointestinal tract. We reported previously that the fermentationof milk at constant pH 6 by L. helveticus R389 increased its content of peptide fractions, and the oraladministration of the non-bacterial fraction (FMSpH6) to mice increased total secretory IgA in theintestinal lumen and enhanced the number of IgA and various cytokines producing cells as well asthe secretion of IL-6 by small intestine epithelial cells. We also demonstrated that this FMSpH6 waseffective for the prevention of Salmonella typhimurium infection in mice. In this work, we studied inmice the impact of the oral administration of the supernatant of milk fermented by L. helveticus R389on the gut physiology by measuring parameters such as calcium channels and E-cadherinexpression, the activation of the biological signal calcineurin and mast and goblet cells, as a way todetermine some mechanisms involved in the immunomodulating effects of the milk fermentationproducts, observed in previous studies. We analyzed the impact of the supernatant of milkfermented by L. helveticus R389 at pH6-controlled on the expression of calcineurin and on thereinforcement of the ephitelial barrier, measuring parameters such as calcium channels and Ecadherinexpression and in the reinforcement of the non-specific immunity determining mast cellsand goblet cells associated to the gut.Results: We observed an enhanced expression of TRPV6 channels in the duodenum, indicating animproved capacity for dietary Ca2+ uptake. We demonstrated an enhanced expression ofcalcineurin in the small intestine, able to upregulate immune parameters such as IL-2 and TNFproduction, with an increase in the number of these cytokines secreting cells. We determined anincrease in the number of mucosal mast cells and goblet cells, which would mean an improved stateof mucosal surveillance at sites of infection.Conclusion: The oral administration of the supernatant of milk fermented by L. helveticus R389enhanced the gut mucosal immunity by improving the mechanisms that reinforce the epithelial andnon-specific barriers and the gut functioning at sites of infection, with an improvement in theexpression of the enzyme calcineurin, an important signal in the network that activates the gutimmune system. The results of this work contribute to revealing the mechanisms underlying theimmunomodulation of the gut immune function by fermented milks with probiotic bacteria.