Immunomodulatory Effect of Lactobacillus casei in a Murine Model of Colon Carcinogenesis

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Immunomodulatory Effect of Lactobacillus casei in a Murine Model of Colon Carcinogenesis Josefina Casas-Solís 1 & María del Rosario Huizar-López 1 María Luisa Pita-López 3 & Anne Santerre 1

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Cesar Antonio Irecta-Nájera 2

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# Springer Science+Business Media, LLC, part of Springer Nature 2019

Abstract We previously reported beneficial effects of the probiotic strain Lactobacillus casei 393 in hindering colon carcinogenesis in a 1,2-dimethylhydrazine (DMH)-induced BALB/c mouse model of colon cancer. In the present study, we investigated the effect of preventive administration of L. casei 393 on the levels of selected pro- and anti-inflammatory circulating cytokines, as well as subpopulations of splenic T cells. The resulting experimental data on IFNγ, TNFα, IL-10, and colon histological features demonstrated that administration of L. casei 2 weeks before DMH treatment impaired the pro-inflammatory effect of DMH, while maintaining the levels of the three cytokines as well as colon histology; it also modulated splenic CD4+, CD8+, and NK T cell subpopulations. The preventive administration of L. casei to DMH-treated mice increased IL-17A synthesis and Treg percentages, further indicating a tumor-protecting role. Together, the results suggest that the colon-cancer-protective properties of L. casei 393 involve the dampening of inflammation through cytokine homeostasis and the maintenance of a healthy T cell subpopulation dynamic. For these reasons, probiotics such as L. casei may contribute to the health of the host as they promote optimal control of the immune response. Further, they may be used as prophylactic agents in combination with standard therapies against colon cancer. Keywords Lactobacillus casei . Colon carcinogenesis . 1, 2-Dimethylhydrazine . Serum cytokines . Splenic T cell subpopulations . Flow cytometry

Introduction Colon cancer (CC) is a malignant tumor of the digestive tract that represents almost 10% of all diagnosed cancers worldwide, and is the third leading cause of cancer-related deaths [1, 2]. Early colon carcinogenesis usually has no or unclear symptoms. Further, the symptoms that do present are often * Anne Santerre [email protected] 1

Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Carretera Guadalajara-Nogales Km 15.5, Las Agujas, CP, 45110 Zapopan, Jalisco, México

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Departamento de Salud, El Colegio de La Frontera Sur, Carretera a Reforma Km15.5 s/n, Ra ElGuieno 2ª Sección, 86280 Villahermosa, Tabasco, México

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Departamento de Ciencias Básicas para la Salud, CIBIMEC, Centro Universitario del Sur, Universidad de Guadalajara, Av. Enrique Arreola Silva 883, CP4900, Cd. Guzmán, Guadalajara, Jalisco, México

associated with other gastrointestinal diseases, so CC progression may go undetected for decades, and ends up not being diagnosed until an advanced stage. Effective treatments for CC exist, including surgical intervention, chemotherapy, and radiotherapy. However, each protocol has limitations,