Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells.

The use of short chain fatty acids to modulate gastrointestinal inflammatory conditions such as ulcerative colitis has produced encouraging results either in animal models or also in clinical trials. Identifying the key cellular and molecular targets of this activity will contribute to establish the appropriate combinations/targeting strategies to maximize the efficacy of anti-inflammatory interventions. In the present work, we evaluated in vitro the interaction of lactate, acetate, propionate and butyrate on cells relevant for innate immune response of the gastrointestinal tract. All molecules tested regulate the production of proinflammatory cytokines by TLR-4 and TLR-5 activated intestinal epithelial cells in a dose response manner. Furthermore SCFAs and lactate modulate cytokine secretion of TLR-activated bone marrow derived macrophages and also TLR-dependent CD40 upregulation in bone marrow derived dendritic in a dose-dependent manner. Butyrate and propionate have been effective at concentrations of 1 to 5mM whereas acetate and lactate produced modulatory effects at concentrations higher than 20-50mM in different assays. Our results indicate that in concentrations similar to found in large bowel lumen, all SCFAs tested and lactate can modulate activity of relevant sentinel cell types activated by TLR signals. Modulatory activity was not inhibited by pertussis toxin treatment indicating that the effects are not related to Gi signaling. The use of these molecules in combined or separately as intervention strategy in conditions where epithelial or myeloid cells are main triggers of the inflammatory situation seems appropriate.

Carbohydrate supplementation during intense exercise and the immune response of cyclists.

OBJECTIVE: To evaluate the effect of carbohydrate supplementation upon some aspects of the immune function in athletes during intense indoor cycling. METHODS: Twelve male athletes cycled for 20 min at a velocity corresponding to 90% of that obtained at the anaerobic threshold and rested for 20 min. This protocol was repeated six times. The athletes received, during the trial, water ad libitum, or a solution of carbohydrate (95% glucose polymers and 5% fructose) at 10% (w/v), 1 g kg h every 20 min, starting at the 10th minute of the first exercise period, plus extra water ad libitum. RESULTS: Exercise induced a reduction in peripheral blood mononuclear cell proliferation (37%) as well as in the production of cytokines by cultured cells (interleukin-1 (IL-1), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), by 37%, 35%, 26% and 16%, respectively). All of these changes were prevented by the ingestion of a carbohydrate drink by the athletes, except that in IFN-gamma production, which was equally decreased (17%) after the second trial. The concentration of plasma glutamine, an important fuel for immune cells, was decreased in the placebo group but maintained in the group that received carbohydrate. CONCLUSION: Carbohydrate supplementation affects positively the immune response of cyclists by avoiding or minimizing changes in plasma glutamine concentration.