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Design and validation of an orally administrated active L. fermentum-L. acidophilus probiotic formulation using colorectal cancer Apc Min/+ mouse model

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Abstract

Probiotics have been shown to have beneficial properties in attenuating the risk of colorectal cancer (CRC) development. However, functional evidence to support such effects for some probiotic bacteria are relatively unknown. Here, we document a significant antioxidant, anti-proliferative and pro-apoptotic activities of Lactobacillus acidophilus ATCC 314 and Lactobacillus fermentum NCIMB 5221 on CRC cells, particularly when used in combination (La-Lf). Furthermore, a superior synergistic activity on the inhibition of tumor growth and modulation of cell proliferation and epithelial markers in the Apc Min/+ CRC mouse model was explored, based on the expression levels of Ki-67, E-cadherin, β-catenin, and cleaved caspase-3 (CC3) proteins. The anti-cancer activity of La-Lf co-culture was significantly enhanced in vitro with significant reduced proliferation (38.8 ± 6.9 %, P = 0.009) and increased apoptosis (413 RUL, P < 0.001) towards cancer cells, as well as significant protection of normal colon cell growth from toxic treatment (18.6 ± 9.8 %, P = 0.001). La-Lf formulation (1010cfu/animal/day) altered aspects of intestinal tumorigenesis by significantly reducing intestinal tumor multiplicity (1.7-fold, P = 0.016) and downregulating cellular proliferation markers, including β-catenin (P = 0.041) and Ki-67 (P = 0.008). In conclusion, La-Lf showed greater protection against intestinal tumorigenesis supporting a potential use as a biotherapeutic for the prevention of CRC.

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Acknowledgments

The authors would like to acknowledge a Canadian Institute of Health Research (CIHR) grant (MPO 64308) and grants from Micropharma Limited to Dr. Satya Prakash, a Fonds de Recherche du Québec–Santé (FRSQ) Doctoral Awards and a Faculty of Medicine George G. Harris Fellowship to Imen Kahouli. The authors thank the Comparative Medicine and Animal Resources Centre (McGill University) and Dr. Martin Lapointe for his assistance with histopathological analysis. The authors acknowledge the assistance of Dr. Anis Riahi (Department of Neurology, Military Hospital of Tunis, Tunisia), as well as Nadia R. Hindri (Clinical Biology Laboratory, Salah Azaiz Institute, Tunisia) in the study design and data interpretation.

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Authors and Affiliations

  1. Department of Experimental Medicine, Faculty of Medicine, McGill University, 1110 Pine Avenue West, Montreal, QC, H3A 1A3, Canada

    Imen Kahouli & Satya Prakash

  2. Department of Biomedical Engineering, Faculty of Medicine, Biomedical Technology and Cell Therapy Research Laboratory, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada

    Imen Kahouli, Meenakshi Malhotra, Susan Westfall & Satya Prakash

  3. Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada

    Imen Kahouli & Moulay A. Alaoui-Jamali

  4. Department of Microbiology, Immunology and Infectious Diseases, CHU St. Justine Research Center, University of Montreal, 3175 Cote-Ste-Catherine, Montréal, QC, H3T 1C5, Canada

    Meenakshi Malhotra

  5. Departments of Medicine and Oncology, Faculty of Medicine, Gerald Bronfman Centre, McGill University, Room 210, 546 Pine Avenue West, Montreal, QC, H2W 1S6, Canada

    Moulay A. Alaoui-Jamali

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  1. Imen Kahouli
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  2. Meenakshi Malhotra
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  4. Moulay A. Alaoui-Jamali
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  5. Satya Prakash
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Correspondence to Satya Prakash.

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Funding

This study was funded by a Canadian Institute of Health Research (CIHR) grant (MPO 64308).

Conflict of interest

Imen Kahouli declares that she has no conflict of interest. Dr. Meenakshi Malhotra declares that she has no conflict of interest. Susan Westfall declares that she has no conflict of interest. Dr. Moulay A. Alaoui-Jamali declares that he has no conflict of interest. Dr. Satya Prakash declares that he has no conflict of interest.

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All applicable international, national, and institutional guidelines for the use and care of animals were followed.

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Kahouli, I., Malhotra, M., Westfall, S. et al. Design and validation of an orally administrated active L. fermentum-L. acidophilus probiotic formulation using colorectal cancer Apc Min/+ mouse model. Appl Microbiol Biotechnol 101, 1999–2019 (2017). https://doi.org/10.1007/s00253-016-7885-x

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