The isoflavone genistein inhibits internalization of enteric bacteria by cultured Caco-2 and HT-29 enterocytes

The dietary isoflavone genistein is the focus of much research involving it s role as a potential therapeutic agent in a variety of diseases, including cancer and heart disease. However, there is recent evidence that dietary g enistein may also have an inhibitory effect on extraintestinal invasion of enteric bacteria. To study the effects of genistein on bacterial adherence and internalization by confluent enterocytes, Caco-2 and HT-29 enterocytes (cultivated for 15-18 d and 21-24 d, respectively) were pretreated for 1 h with 0, 30, 100, or 300 mu mol/L genistein, followed by 1-h incubation with pure cultures of Listeria monocytogenes, Salmonella typhimurium, Proteus m irabilis, or Escherichia coli. Pretreatment of Caco-2 and HT-29 enterocytes with genistein inhibited bacterial internalization in a dose-dependent man ner (r = 0.60-0.79). Compared to untreated enterocytes, 1-h pretreatment wi th 300 mu mol/L genistein was generally associated with decreased bacterial internalization (P < 0.05) without a corresponding decrease in bacterial a dherence. Using Caco-2 cell cultures, decreased bacterial internalization w as associated with increased integrity of enterocyte tight junctions [measu red by increased transepithelial electrical resistance (TEER)], with altera tions in the distribution of enterocyte perijunctional actin filaments (vis ualized by fluorescein-labeled phalloidin), and with abrogation of the decr eased TEER associated with S. typhimurium and E. coli incubation with the e nterocytes (P < 0.01). Thus, genistein was associated with inhibition of en terocyte internalization of enteric bacteria by a mechanism that might be r elated to the integrity of the enterocyte tight junctions, suggesting that genistein might function as a barrier-sustaining agent, inhibiting extraint estinal invasion of enteric bacteria.