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Protective effects of a probiotic yoghurt in a murine model of breast cancer undergoing chemotherapy

Published online by Cambridge University Press:  28 October 2025

Martín Nicolás Cerasuolo
Affiliation:
Centro de Referencia para Lactobacilos (CERELA, CONICET-FML-FECIC) , Chacabuco 145, (T4000ILC) San Miguel de Tucumán, Tucumán, Argentina
Jean Guy LeBlanc*
Affiliation:
Centro de Referencia para Lactobacilos (CERELA, CONICET-FML-FECIC) , Chacabuco 145, (T4000ILC) San Miguel de Tucumán, Tucumán, Argentina
Alejandra de Moreno de LeBlanc*
Affiliation:
Centro de Referencia para Lactobacilos (CERELA, CONICET-FML-FECIC) , Chacabuco 145, (T4000ILC) San Miguel de Tucumán, Tucumán, Argentina
*
Corresponding authors: Alejandra de Moreno de LeBlanc; Email: demoreno@cerela.org.ar, Jean Guy LeBlanc; Email: leblanc@cerela.org.ar
Corresponding authors: Alejandra de Moreno de LeBlanc; Email: demoreno@cerela.org.ar, Jean Guy LeBlanc; Email: leblanc@cerela.org.ar

Abstract

Breast cancer is one of the most frequently diagnosed cancers worldwide. Although chemotherapy remains a prevalent treatment, it negatively affects patients’ quality of life. In this regard, probiotics emerge as possible adjuvants. The aim of this study was to evaluate two lactic acid bacteria (LAB) selected for their immunomodulatory properties, Streptococcus thermophilus CRL807 and Lactobacillus delbrueckii subsp. bulgaricus CRL864, in a breast cancer model undergoing chemotherapy with capecitabine or 5-fluorouracil (5-FU). 4T1 breast cancer cells were injected into the upper mammary gland of adult female mice. After tumour reached an appropriate size, mice were separated into groups (n 10) receiving either individual LAB (100 µl of 9 ± 1 × 108 CFU/ml) or yoghurt (2 ± 1108 CFU/ml ad libitum) with or without chemotherapy. The results showed that administration of LAB or yoghurt resulted in a significant reduction in tumour size and weight (about 50%), modulating the immune response, with increases of IL-10 in mice with smaller tumours, and without affecting chemotherapy. Furthermore, consumption of LAB or yoghurt decreased the negative side effects associated with these treatments. Yoghurt showed the best results in preventing weight loss, with lower mortality (20 % v. 40 % for 5-FU treatment), maintaining intestinal histology and modulating plasma cytokines, with increases of IL-10. In conclusion, administration of this probiotic yoghurt was safe in cancer hosts undergoing chemotherapy, reducing some associated negative side effects without interfering with the primary cancer treatment. Furthermore, this yoghurt showed beneficial properties against the tumour, modulating the host’s immune response.

Information

Type
Research Article
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

Jean Guy LeBlanc and Alejandra de Moreno de LeBlanc participated equally in this work.

References

FAO/WHO (2002) Probiotics in Food. http://www.fao.org/3/a-a0512e.pdf (accessed 13 October 2025).Google Scholar
Homayoni Rad, A, Mehrabany, EV, Alipoor, B, et al. (2012) Do probiotics act more efficiently in foods than in supplements? Nutrition 28, 733736.CrossRefGoogle ScholarPubMed
Ibrahim, SA, Yeboah, PJ, Ayivi, RD, et al. (2023) A review and comparative perspective on health benefits of probiotic and fermented foods. Int J Food Sci Technol 58, 49484964.CrossRefGoogle Scholar
Soemarie, YB, Milanda, T & Barliana, MI (2021) Fermented foods as probiotics: a review. J Adv Pharm Technol Res 12, 335339.CrossRefGoogle ScholarPubMed
Flach, J, van der Waal, MB, van den Nieuwboer, M, et al. (2018) The underexposed role of food matrices in probiotic products: reviewing the relationship between carrier matrices and product parameters. Crit Rev Food Sci Nutr 58, 25702584.CrossRefGoogle ScholarPubMed
Aryana, KJ & Olson, DW (2017) A 100-year review: yogurt and other cultured dairy products. J Dairy Sci 100, 998710013.CrossRefGoogle ScholarPubMed
Hadjimbei, E, Botsaris, G & Chrysostomou, S (2022) Beneficial effects of yoghurts and probiotic fermented milks and their functional food potential. Foods 11, 2691.CrossRefGoogle ScholarPubMed
Le Roy, CI, Kurilshikov, A, Leeming, ER, et al. (2022) Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome. BMC Microbiol 22, 39.CrossRefGoogle ScholarPubMed
Savaiano, DA & Hutkins, RW (2021) Yogurt, cultured fermented milk, and health: a systematic review. Nutr Rev 79, 599614.CrossRefGoogle ScholarPubMed
Guarner, F, Perdigon, G, Corthier, G, et al. (2005) Should yoghurt cultures be considered probiotic? Br J Nutr 93, 783786.CrossRefGoogle ScholarPubMed
Arena, MP, Caggianiello, G, Russo, P, et al. (2015) Functional starters for functional yogurt. Foods 4, 1533.CrossRefGoogle ScholarPubMed
Hill, C, Guarner, F, Reid, G, et al. (2014) Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 11, 506514.CrossRefGoogle ScholarPubMed
Sung, H, Ferlay, J, Siegel, RL, et al. (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71, 209249.Google ScholarPubMed
Claessens, AKM, Ibragimova, KIE, Geurts, SME, et al. (2020) The role of chemotherapy in treatment of advanced breast cancer: an overview for clinical practice. Crit Rev Oncol Hematol 153, 102988.CrossRefGoogle ScholarPubMed
Basile, D, Di Nardo, P, Corvaja, C, et al. (2019) Mucosal injury during anti-cancer treatment: from pathobiology to bedside. Cancers (Basel) 11, 857.CrossRefGoogle Scholar
Thomsen, M & Vitetta, L (2018) Adjunctive treatments for the prevention of chemotherapy- and radiotherapy-induced mucositis. Integr Cancer Ther 17, 10271047.CrossRefGoogle ScholarPubMed
Rodriguez-Arrastia, M, Martinez-Ortigosa, A, Rueda-Ruzafa, L, et al. (2021) Probiotic supplements on oncology patients’ treatment-related side effects: a systematic review of randomized controlled trials. Int J Environ Res Public Health 18, 4265.CrossRefGoogle ScholarPubMed
Lu, K, Dong, S, Wu, X, et al. (2021) Probiotics in cancer. Front Oncol 11, 638148.CrossRefGoogle ScholarPubMed
de Moreno de LeBlanc, A & Perdigon, G (2004) Yogurt feeding inhibits promotion and progression of experimental colorectal cancer. Med Sci Monit 10, BR96–104.Google Scholar
del Carmen, S, de Moreno de LeBlanc, A, Martin, R, et al. (2014) Genetically engineered immunomodulatory Streptococcus thermophilus strains producing antioxidant enzymes exhibit enhanced anti-inflammatory activities. Appl Environ Microbiol 80, 869877.CrossRefGoogle ScholarPubMed
Del Carmen, S, de Moreno de LeBlanc, A & LeBlanc, JG (2016) Development of a potential probiotic yoghurt using selected anti-inflammatory lactic acid bacteria for prevention of colitis and carcinogenesis in mice. J Appl Microbiol 121, 821830.CrossRefGoogle ScholarPubMed
Raibaud, P, Caulet, M, Galpin, JV, et al. (1961) Studies on the bacterial flora of the alimentary tract of pigs II. Streptococci: selective enumeration and differentiation of the dominant group. J Appl Bacteriol 24, 285291.CrossRefGoogle Scholar
Levit, R, Savoy de Giori, G, de Moreno de LeBlanc, A, et al. (2021) Evaluation of vitamin-producing and immunomodulatory lactic acid bacteria as a potential co-adjuvant for cancer therapy in a mouse model. J Appl Microbiol 130, 20632074.CrossRefGoogle ScholarPubMed
Méndez Utz, VE, Pérez Visñu, KD, Perdigón, G, et al. (2021) Milk fermented by Lactobacillus casei CRL431 administered as an immune adjuvant. Appl Microbiol Biotechnol 105, 327340.CrossRefGoogle Scholar
Levit, R, Savoy de Giori, G, de Moreno de LeBlanc, A, et al. (2018) Protective effect of the riboflavin-overproducing strain Lactobacillus plantarum CRL2130 on intestinal mucositis in mice. Nutr 54, 165172.CrossRefGoogle ScholarPubMed
Aragon, F, Carino, S, Perdigon, G, et al. (2015) Inhibition of growth and metastasis of breast cancer in mice by milk fermented with Lactobacillus casei CRL 431. J Immunother 38, 185196.CrossRefGoogle ScholarPubMed
Méndez Utz, VE, Pérez Visñuk, D, Perdigón, G, et al. (2021) Milk fermented by Lactobacillus casei CRL431 administered as an immune adjuvant in models of breast cancer and metastasis under chemotherapy. Appl Microbiol Biotechnol 105, 327340.CrossRefGoogle Scholar
Joensuu, H, Kellokumpu-Lehtinen, PL, Huovinen, R, et al. (2022) Adjuvant capecitabine for early breast cancer: 15-year overall survival results from a randomized trial. J Clin Oncol 40, 10511058.CrossRefGoogle ScholarPubMed
Oner, I, Turkel, A, Karacin, C, et al. (2023) Adjuvant capecitabine after neoadjuvant chemotherapy in triple negative breast cancer with lymph node metastasis. J Coll Physicians Surg Pak 33, 10121018.Google ScholarPubMed
Xu, D, Chen, X, Li, X, et al. (2019) Addition of capecitabine in breast cancer first-line chemotherapy improves survival of breast cancer patients. J Cancer 10, 418429.CrossRefGoogle ScholarPubMed
Shahrokni, A, Rajebi, MR & Saif, MW (2009) Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: a challenge or a dilemma? Clin Colorectal Cancer 8, 231234.Google ScholarPubMed
DuPre, SA & Hunter, KW Jr (2007) Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: association with tumor-derived growth factors. Exp Mol Pathol 82, 1224.CrossRefGoogle ScholarPubMed
Zhang, W, Zhang, Y, Li, Y, et al. (2022) Lacticaseibacillus rhamnosus probio-M9-driven mouse mammary tumor-inhibitory effect is accompanied by modulation of host gut microbiota, immunity, and serum metabolome. Nutrients 15, 5.CrossRefGoogle ScholarPubMed
Thu, MS, Ondee, T, Nopsopon, T, et al. (2023) Effect of probiotics in breast cancer: a systematic review and meta-analysis. Biology (Basel) 12, 280.Google ScholarPubMed
Muradás, TC, Freitas, RD, Gonçalves, JI, et al. (2024) Potential antitumor effects of short-chain fatty acids in breast cancer models. Am J Cancer Res 14, 19992019.CrossRefGoogle ScholarPubMed
Al-Qadami, GH, Secombe, KR, Subramaniam, CB, et al. (2022) Gut microbiota-derived short-chain fatty acids: impact on cancer treatment response and toxicities. Microorganisms 10, 2048.CrossRefGoogle ScholarPubMed
Dahlgren, D, Sjöblom, M, Hellström, PM, et al. (2021) Chemotherapeutics-induced intestinal mucositis: pathophysiology and potential treatment strategies. Front Pharmacol 12, 681417.CrossRefGoogle ScholarPubMed
Mirzadeh, MA, Eslami, M, Ghanbari, A, et al. (2024) Coadministration of doxorubicin with vitamin D3, Lactobacillus acidophilus, and Lactobacillus casei in the 4T1 mouse model of breast cancer: anticancer and enteroprotective effects. Med Oncol 41, 111.CrossRefGoogle ScholarPubMed
Nama, ASA, Sandeepa, GM, Buddolla, V, et al. (2025) Advances in understanding therapeutic mechanisms of probiotics in cancer management, with special emphasis on breast cancer: a comprehensive review. Eur J Pharmacol 995, 177410.CrossRefGoogle ScholarPubMed
Qian, X, Qian, X, Chen, X, et al. (2015) The anti-proliferative effect of 5-fluorouracil on tumor is highly associated with the renewal of peripheral white blood cells. J Cancer Ther 6, 594600.CrossRefGoogle Scholar
Wang, C, Chen, YG, Gao, JL, et al. (2015) Low local blood perfusion, high white blood cell and high platelet count are associated with primary tumor growth and lung metastasis in a 4T1 mouse breast cancer metastasis model. Oncol Lett 10, 754760.CrossRefGoogle Scholar
de Moreno de LeBlanc, A, Matar, C & Perdigon, G (2007) The application of probiotics in cancer. Br J Nutr 98, S105110.CrossRefGoogle ScholarPubMed
Walker Ii, WH, Borniger, JC, Surbhi Zalenski, AA, et al. (2017) Mammary tumors induce central pro-inflammatory cytokine expression, but not behavioral deficits in Balb/C mice. Sci Rep 7, 8152.CrossRefGoogle Scholar
Xue, K, Li, J & Huang, R (2024) The immunoregulatory role of gut microbiota in the incidence, progression, and therapy of breast cancer. Front Cell Infect Microbiol 14, 1411249.CrossRefGoogle ScholarPubMed
Ahmad, MF, Ahmad, FA, Alsayegh, AA, et al. (2025) Probiotics and cancer: mechanistic insights and organ-specific impact. Biomolecules 15, 879.CrossRefGoogle ScholarPubMed