brevis on human health, our results indicate that during transit through the stomach (1h 40 min in our assay) as well as in contact with Caco-2 cells (8 h) the bacteria could VRT752271 produce around 0.5 mM tyramine (87 mg L-1). This should selleck inhibitor not be harmful for healthy individuals, since an average of 500 mg of orally administrated tyramine is required to increase systolic blood pressure [33]. However, tyramine can be
particularly toxic to patients receiving monoamine oxidase (MAO) inhibitors. Gastrointestinal MAO is essential for the breakdown of tyramine and it has been reported that as little as 6 mg of tyramine is sufficient to produce hypertension in humans treated with MAO inhibitors [34]. Ethanol also inhibits MAO. Thus the expected low toxic effect due to low levels of tyramine produced by L. brevis during wine fermentation could be potentiated by the simultaneous ingestion of high ethanol content beverages. Moreover, the production of putrescine by this bacterium could be also
harmful. The polyamines, including putrescine, play a role in the maturation of the intestine, even when administrated orally [35]. Polyamines administrated orally can act as growth factors with beneficial or detrimental effects, depending on their concentration [36] and there is evidence suggesting that putrescine click here can cause malignancy in GIT cells [37]. It is estimated that the daily intake of polyamines in the diet is in the range of 350–550 selleck μmol. Thus, the amount of putrescine (around 140 μM) produced by L. brevis in 1 h 40 min in the gastric environment seem to be of little concern. However, the 1.3-1.9 mM production of putrescine in the presence of Caco-2 epithelial cells during 8 h, is more worrying, especially if L. brevis is able to colonize, even transiently, the small intestine. Conclusions L. brevis IOEB 9809 produced both tyramine and putrescine under all conditions in an in vitro model that simulated the normal physiological conditions in the human digestive tract,
as well as in the presence of Caco-2 epithelial cells. Under mild gastric stress bacterial survival improved in the presence of BA precursors and a synchronous transcriptional activation of the tyramine and putrescine biosynthetic pathways was detected. These results suggest that BA production may be a mechanism that increases bacterial survival under acid stress. The results also indicate that it may be possible for viable cells of L. brevis IOEB 9809 to pass from the stomach into the duodenum. L. brevis IOEB 9809 cells were able to adhere to Caco2 cells, which suggests that they may be able to adhere to human intestinal epithelium. However, this would not necessarily guarantee that L. brevis IOEB 9809 would colonise the lower intestine as the impact of competition with other resident microorganisms, and the gut’s innate defence mechanisms has not been assessed for this organism.