Dietary Indole-3-carbinol alleviated spleen enlargement, enhanced IgG response in C3H/HeN mice infected with Citrobacter rodentium

Authors: WU, YANBEI - Beijing Advanced Innovation Center For Food Nutrition And Human Health, Beijing Technology & Busine; WANG, JIAN - Beijing Advanced Innovation Center For Food Nutrition And Human Health, Beijing Technology & Busine; HE, QIANG - Sichuan University; YU, LIANGLI - University Of Maryland; Pham, Quynhchi; Cheung, Lumei; ZHANG, ZHI - University Of Maryland; KIM, YOUNG - National Cancer Institute (NCI, NIH); Smith, Allen; Wang, Thomas - Tom

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/11/2020
Publication Date: 10/15/2020
Citation: Wu, Y., Wang, J., He, Q., Yu, L., Pham, Q., Cheung, L., Zhang, Z., Kim, Y.S., Smith, A.D., Wang, T.T. 2020. Dietary Indole-3-carbinol alleviated spleen enlargement, enhanced IgG response in C3H/HeN mice infected with Citrobacter rodentium. Nutrients. 12(10)3148. https://doi.org/10.3390/nu12103148.
DOI: https://doi.org/10.3390/nu12103148

Interpretive Summary: Identifying food-derived bio-actives and their mechanisms of action remain critical in understanding the role of diet in the prevention of disease including food borne pathogens. Enteropathogenic and enterohemorrhagic Escherichia coli are important enteric pathogens that induce hemorrhagic colitis, or even fatal hemolytic uremic syndrome. Emerging evidence shows that some bio-actives derived from fruits and vegetables may serve as alternatives to antibiotics for overcoming multidrug resistant E. coli infections. In this study, the Citrobacter rodentium (Cr) infection model was utilized to mimic E. coli-induced acute intestinal inflammation, and the effects of a cruciferous vegetable-derived cancer protective compound, indole-3-carbinol (I3C), on the immune responses of Cr-susceptible C3H/HeN mice were investigated. Dietary I3C significantly inhibited the loss of body weight and the increase in spleen size in Cr infected mice. In addition, I3C treatment reduced the inflammatory response to Cr infection by maintaining anti-inflammatory cytokine IL-22 mRNA levels while reducing tne expression of other pro-inflammatory cytokines including IL17A, IL6, IL1ß, TNF-a, and IFN-y. Moreover, the serum cytokine levels of IL17, TNF-a, IL12p70 and G-CSF in serum also was down-regulated by I3C in Cr-infected mice. Additionally, dietary I3C specifically enhanced the Cr-specific IgG response to Cr infection. In general, dietary I3C reduced the Cr-induced pro-inflammatory response in susceptible C3H/HeN mice, alleviated the physiological changes and tissue damage induced by Cr infection, but not Cr colonization. The information will benefit basic, translational scientists, as well as regulatory scientists who are interested in antibiotics alternatives in protection against food borne pathogens.

Technical Abstract: Enteropathogenic and enterohemorrhagic Escherichia coli are important enteric pathogens that induce hemorrhagic colitis, or even fatal hemolytic uremic syndrome. Emerging evidence shows that some bio-actives derived from fruits and vegetables may serve as alternatives to antibiotics for overcoming multidrug resistant E. coli infections. In this study, the Citrobacter rodentium (Cr) infection model was utilized to mimic E. coli-induced acute intestinal inflammation, and the effects of a cruciferous vegetable-derived cancer protective compound, indole-3-carbinol (I3C), on the immune responses of Cr-susceptible C3H/HeN mice were investigated. Dietary I3C significantly inhibited the loss of body weight and the increase in spleen size in Cr infected mice. In addition, I3C treatment reduced the inflammatory response to Cr infection by maintaining anti-inflammatory cytokine IL-22 mRNA levels while reducing the expression of other pro-inflammatory cytokines including IL17A, IL6, IL1ß, TNF-a, and IFN-y. Moreover, the serum cytokine levels of IL17, TNF-a, IL12p70 and G-CSF in serum also was down-regulated by I3C in Cr-infected mice. Additionally, dietary I3C specifically enhanced the Cr-specific IgG response to Cr infection. In general, dietary I3C reduced the Cr-induced pro-inflammatory response in susceptible C3H/HeN mice, alleviated the physiological changes and tissue damage induced by Cr infection, but not Cr colonization.