Supplementation with engineered Lactococcus lactis improves the folate status in deficient rats

ObjectiveThe aim of this study was to establish the bioavailability of different folates produced by engineered Lactococcus lactis strains using a rodent depletion–repletion bioassay.MethodsRats were fed a folate-deficient diet, which produces a reversible subclinical folate deficiency, supplemented with different L. lactis cultures that were added as the only source of folate. Three bacterial strains that overexpressed the folC, folKE, or folC + KE genes were used. These strains produce folates with different poly glutamyl tail lengths. The growth response of the rats and the concentration of folates in different organs and blood samples were monitored.ResultsThe folate produced by the engineered strains was able to compensate the folate depletion in the diet and showed similar bioavailability compared with commercial folic acid that is normally used for food fortification. Folate concentrations in organ and blood samples increased significantly in animals that received the folate-producing strains compared with those that did not receive bacterial supplementation. Hematologic studies also showed that administration of the L. lactis strains was able to revert a partial megaloblastic anemia caused by folate deficiency. No significant differences were observed in the bioavailability of folates containing different glutamyl tail lengths.ConclusionTo our knowledge, this is the first study that demonstrated that folates produced by engineered lactic acid bacteria represent a bioavailable source of this essential vitamin.