Abstract
Zinc deficiency enhances infectious diarrhea whereas probiotics may inhibit pathogen enterocyte invasion. The effect of probiotics on zinc-deficient versus normal human intestinal epithelium (Caco-2 and T-84) with regard to invasion and subsequent inflammatory response by Salmonella typhimurium was determined. Cells were infected with pathogens and preincubated with media conditioned by several lactobacilli or Bifidobacterium bifidum 12. Pathogen invasion was quantified, inflammation was determined by IL-8 secretion, and MAP kinase activation in the epithelium was analyzed. Probiotic inhibiting factors were partially characterized based on physicochemical properties. Zinc deficiency allowed for greater pathogen invasion and enhanced IL-8 secretion. Probiotic conditioned media reduced activation of proinflammatory signaling via the ERK and p38 pathway. Probiotic factors reverse increased susceptibility of zinc-deficient enterocytes to S. typhimurium invasion, suggesting an additive protective effect of probiotics in zinc deficiency. Probiotic conditioned media but not bacteria inhibited pathogen invasion and IL-8 production in zinc deficient enterocytes. Probiotic inhibitory factors are stable to treatment with proteases, deoxyribonucleases (DNAses), ribonucleases (RNAse), strong acid, and heat.
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Abbreviations
- MRS:
-
Mann Rogosa Sharpe
- PMA:
-
phorbol 12-myristate 13-acetate
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Acknowledgements
The authors thank Dr. Chitra Amarasiriwardena, Trace-metal Laboratory, Channing Laboratory, Harvard Medical School, Boston, MA, for determining zinc concentrations by ICP-MS (Varian Instruments, Palo Alto, CA).
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This review was supported by funding from the National Institutes of Health [(PO1 DK33506, P30 DK40561, R37 HD12437 (W.A.W.), ROI DK70260 (W.A.W., N.N.N.)], by a Fulbright Scholarship from the United States Department of State (I.J.B.), and by a research fellowship from Mead Johnson Nutritionals (I.J.B.).
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Broekaert, I., Nanthakumar, N. & Walker, W. Secreted Probiotic Factors Ameliorate Enteropathogenic Infection in Zinc-Deficient Human Caco-2 and T84 Cell Lines. Pediatr Res 62, 139–144 (2007). https://doi.org/10.1203/PDR.0b013e31809fd85e
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DOI: https://doi.org/10.1203/PDR.0b013e31809fd85e
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