Evidence of the cytotoxic and synergistic effects of the biogenic amines tyramine and histamine, which can accumulate at high concentrations in cheese because of the decarboxylative metabolism of some LAB

Abstract

Lactic acid bacteria (LAB) play an essential role in the production of a large diversity of fermented foods. The long and harmless history of use of LAB in food fermentations has resulted in them being generally recognized as safe. However, some LAB possess enzymatic activities that produce undesirable toxic compounds, such as the biogenic amines (BA) tyramine and histamine. In cheese, one of the foods in which the highest concentrations of BA can be found, they are produced predominantly by LAB. More specifically, Enterococcus faecalis is the main responsible for the accumulation of tyramine, while Lactobacillus parabuchneri is the species mainly responsible for the accumulation of histamine. Although the European Food Safety Authority (EFSA) deems tyramine and histamine to be the most toxic BA, it also concludes that our present knowledge of their toxicity is limited, and that further research is needed.

In this communication, we present an analysis of the in vitro cytotoxicity of tyramine and histamine, individually and in combination, towards intestinal cells in culture. To perform these analyses, we have developed an in vitro model of the human intestinal epithelium based on the HT29 cell line and the Real Time Cell Analyzer (RTCA) technology. Tyramine and histamine were found to be cytotoxic at concentrations commonly found in some types of cheese. Surprisingly, tyramine -a BA for which no legal limit has been established- had a stronger and more rapid cytotoxic effect than histamine. Their mode of action was also different, while tyramine caused cell necrosis, histamine induced apoptosis. We further found that tyramine and histamine have synergistic cytotoxicity in the range of concentrations that can be found in foods.