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EFFECTS OF PROBIOTIC TREATMENT IN ENTEROCHROMAFFIN CELL FUNCTION, INFLAMMATION AND HOST DEFENSE IN ENTERIC INFECTION
J McClemens1, P Forsythe2, H Wang1, A Park1, J Bienenstock2, W Khan1
1Farncombe Family Digestive Health Research Institute; 2Department of Pathology and Molecular Biology, McMaster University, Hamilton, Ontario
Aims: The gastrointestinal (GI) tract contains the largest endocrine organ in the body. The most well characterized subset of GI endocrine cells are enterochromaffin (EC) cells, which synthesize and release serotonin (5-hydroxytryptamine, 5-HT) in the gut. 5-HT is an important enteric signaling molecule of the GI tract that influences both the physiology and the immune responses of the gut as well as gut homeostasis. 5-HT has been implicated in a number of GI diseases including inflammatory bowel disease, functional disorders like irritable bowel syndrome, and in a number of enteric infections. Probiotic bacteria are being investigated as a possible treatment to many GI diseases due to their beneficial effects on modifying the disease by favorably altering the immune system. The aim of this study is to develop a probiotic bacteria based strategy to modulate endocrine cell function in relation to inflammation and host defense in gut. Utilizing a well defined model of enteric parasite infection, Trichuris muris in mouse, we examined the effect of treatment with probiotic Lactobacillus reuteri on EC function, immune and inflammatory responses in gut, and host defense.
Methods: Fifty male C57BL/6 mice were gavaged with ~300 eggs of T.muris, and treated orally with probiotic (1x109 cfu Lactobacillus reuteri), or medium (0.2mL Man-Rogosa-Sharpe Liquid Medium, MRS) everyday for 14 days beginning one day before infection. Mice were sacrificed on days 7, 10, 15, 30 post-infection (pi) to examine 5-HT expressing EC cells in colon tissue by immunohistochemistry, amount of 5-HT in colon by ELISA, cytokines, and worm burden.
Results: Probiotic treated infected mice showed a significant decrease in number of worms in the intestine on days 21 and 29 pi (p<0.05). There was a significant decrease in 5-HT expressing EC cells in the colon on day 15 pi (p<0.05) in probiotic treated infected mice as compared to that in medium treated mice. This was correlated with significant down-regulation of production of proinflammatory cytokines [(IL-12p70 and TNF-alpha) (p<0.05)] in probiotic treated infected mice.
Conclusions: These data demonstrate that probiotic treatment can modulate EC cell function, immune and inflammatory responses in gut, and promote worm expulsion from GI tract. In addition to enhancing our understanding on the beneficial effect of probiotics in gut inflammation and host defense, this research provides new information on endocrine function in gut in the context of EC cells.