THE EFFICACY OF ORALLY ADMINISTERING LACTOBACILLUS CASEI SHIROTA IN ALLEVIATING SIGNS OF DRY EYES IN MICE MODELS
Keywords:
Lactobacillus casei Shirota, dry eye disease, probiotics, tear quantity, tear quality, gut-eye axisAbstract
This study explores the efficacy of orally administering Lactobacillus casei Shirota (LCS) in alleviating the signs of dry eye in male ICR mice models. Using an experimental research design, twenty-six (26) male ICR mice were subjected to dry eye induction through the topical application of 0.2% benzalkonium chloride (BAC) twice daily for one week. The mice were then randomly assigned to a control group (n = 13), which received 300 µL of phosphate-buffered saline (PBS), and an experimental group (n = 13), which received 300 µL of PBS containing 1 × 10⁹ colony-forming units (CFU) of Lactobacillus casei Shirota. Tear quantity and tear film quality were assessed using the Schirmer’s test and the tear break-up time (TBUT) test, respectively. Topical application of 0.2% BAC successfully induced dry eye in both groups. Oral administration of PBS alone did not alleviate the signs of dry eye in the control group, whereas the experimental group that received LCS showed a statistically significant increase in both tear quantity and tear film quality (p < 0.05). These findings indicate that orally administering Lactobacillus casei Shirota can alleviate the signs of dry eye disease in mice models, as reflected in the improvement of tear quantity and quality, and suggest that this probiotic strain may hold potential as a therapeutic approach for dry eye disease.
References
Balcombe, J. P., Barnard, N. D., & Sandusky, C. (2004). Laboratory routines cause animal stress. Journal of the American Association for Laboratory Animal Science, 43(6), 42–51.
Bello, M., Morales-Farfán, A., Martínez-Colín, E. J., Lezama, I., & Lamas, M. (2024). Optimizing tear collection in mice for mRNA and protein analysis. Journal of Visualized Experiments, (209), e66955.
Bloemendaal, M., Szopinska-Tokov, J., Belzer, C., Boverhoff, D., Papalini, S., Michels, F., Hemert, S. V., Vasquez, A. A., & Aarts, E. (2021). Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress: Exploratory analyses. Translational Psychiatry, 11, Article 300. https://doi.org/10.1038/s41398-021-01404-9
Borrelli, M., Frings, A., Geerling, G., & Finis, D. (2020). Gender-specific differences in signs and symptoms of dry eye disease. Current Eye Research, 46(3), 294–301. https://doi.org/10.1080/02713683.2020.1801758
Boyd, K. (2023, November 27). What is dry eye? Symptoms, causes and treatment. American Academy of Ophthalmology. https://www.aao.org/eye-health/diseases/what-is-dry-eye
Carpena-Torres, C., Pintor, J., De Lara, M. J. P., Huete-Toral, F., Crooke, A., Pastrana, C., & Carracedo, G. (2020). Optimization of a rabbit dry eye model induced by topical instillation of benzalkonium chloride. Journal of Ophthalmology, 2020, 1–10. https://doi.org/10.1155/2020/7204951
Chang, C. J., Lin, T. L., Tsai, Y. L., Wu, T. R., Lai, W. F., Lu, C. C., & Lai, H. C. (2019). Next generation probiotics in disease amelioration. Journal of Food and Drug Analysis, 27(3), 615–622. https://doi.org/10.1016/j.jfda.2018.12.011
Chen, F., & Murakami, A. (2022). Application of animal models in interpreting dry eye disease. Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.830592
Chen, L. H., Pan, C. H., Huang, S. Y., Chan, C. H., & Huang, H. Y. (2021). The immunomodulatory effects of long-term supplementation with Lactobacillus casei Shirota depend on ovalbumin presentation in BALB/c mice. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-98791-2
Chen, L., Chang, S., Chang, H., Wu, C., Pan, C., Chang, C., Chan, C., & Huang, H. (2021). Probiotic supplementation attenuates age-related sarcopenia via the gut–muscle axis in SAMP8 mice. Journal of Cachexia, Sarcopenia and Muscle, 13(1), 515–531. https://doi.org/10.1002/jcsm.12849
Chiang, T. (2023, June 6). Dry eye disease (keratoconjunctivitis sicca): Practice essentials, background, anatomy (Dahl, Ed.). Medscape. https://emedicine.medscape.com/article/1210417-overview
Choi, S. H., Oh, J. W., Ryu, J. S., Kim, H. M., Im, S. H., Kim, K. P., & Kim, M. K. (2020). IRT5 probiotics changes immune modulatory protein expression in the extraorbital lacrimal glands of an autoimmune dry eye mouse model. Investigative Ophthalmology & Visual Science, 61(3), 42. https://doi.org/10.1167/iovs.61.3.42
Cristofori, F., Dargenio, V. N., Dargenio, C., Miniello, V. L., Barone, M., & Francavilla, R. (2021). Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: A door to the body. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2021.578386
Deng, F., Li, Y., & Zhao, J. (2019). The gut microbiome of healthy long-living people. Aging, 11(2), 289–290. https://doi.org/10.18632/aging.101771
Food and Drug Administration. (2022). Section 4. Safety information. https://downloads.regulations.gov/FDA-2022-S-0023-0050/content.pdf
Gouveia, K., & Hurst, J. L. (2019). Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice. Scientific Reports, 9(1), 20305.
Huang, W., Tourmouzis, K., Perry, H., Honkanen, R. A., & Rigas, B. (2021). Animal models of dry eye disease: Useful, varied and evolving [Review]. Experimental and Therapeutic Medicine, 22(6), 1394. https://doi.org/10.3892/etm.2021.10830
Hutmacher, F. (2021). What is our most important sense? Frontiers for Young Minds, 9. https://doi.org/10.3389/frym.2021.548120
Kessal, K., Daull, P., Cimbolini, N., Feraille, L., Grillo, S., Docquier, M., Baudouin, C., Brignole-Baudouin, F., & Garrigue, J. S. (2021). Comparison of two experimental mouse dry eye models through inflammatory gene set enrichment analysis based on a multiplexed transcriptomic approach. International Journal of Molecular Sciences, 22(19), 10770. https://doi.org/10.3390/ijms221910770
Khine, W., Ang, X., Chan, Y., Lee, W., Quek, S., Tan, S., Teo, H., Teo, J., Lau, Q., & Lee, Y. K. (2019). Recovery of Lactobacillus casei strain Shirota (LcS) from faeces of healthy Singapore adults after intake of fermented milk. Beneficial Microbes, 10(7), 721–728. https://doi.org/10.3920/bm2018.0173
Kim, D. H., Jung, Y., Moon, J. Y., Kim, S., Ku, Y. A., Jeon, H., Jang, Y. W., Lee, K. H., Ryu, J., Yoon, C., & Kim, M. K. (2021). Therapeutic effects of topical RCI001 on environmental and inflammation-related dry eye mouse models. Investigative Ophthalmology & Visual Science, 62(1322).
Kim, J. E., Nam, J. H., Cho, J. Y., Kim, K. S., & Hwang, D. Y. (2017). Annual tendency of research papers used ICR mice as experimental animals in biomedical research fields. Laboratory Animal Research, 33, 171–174.
Kojima, T., Doğru, M., Kawashima, M., Nakamura, S., & Ohta, M. (2020). Advances in the diagnosis and treatment of dry eye. Progress in Retinal and Eye Research. https://doi.org/10.1016/j.preteyeres.2020.100842
Kuo, Y. K., Lin, I. C., Chien, L. N., Lin, T. Y., How, Y. T., Chen, K. H., Dusting, G. J., & Tseng, C. L. (2019). Dry eye disease: A review of epidemiology in Taiwan, and its clinical treatment and merits. Journal of Clinical Medicine, 8(8), 1227. https://doi.org/10.3390/jcm8081227
Lee, K., Jeong, J. W., Shim, J. J., Hong, H. P., Kim, J. Y., & Lee, J. L. (2023). Lactobacillus fermentum HY7302 improves dry eye symptoms in a mouse model of benzalkonium chloride-induced eye dysfunction and human conjunctiva epithelial cells. International Journal of Molecular Sciences, 24(12), 10378. https://doi.org/10.3390/ijms241210378
Li, H., Wei, F., Li, S., Yan, L., & Lu, P. (2020). The effect of sinomenine eye drops on experimental dry eye in mice. Cutaneous and Ocular Toxicology, 39(4), 389–395. https://doi.org/10.1080/15569527.2020.1840580
Li, J., Wu, H., Liu, Y., & Yang, L. (2020). High fat diet induced obesity model using four strains of mice: Kunming, C57BL/6, BALB/c and ICR. Experimental Animals, 69(3), 326–335.
Martin, S. E., Kraft, C. S., Ziegler, T. R., Millson, E. C., Rishishwar, L., & Martin, G. S. (2023). The role of diet on the gut microbiome, mood and happiness. medRxiv. https://doi.org/10.1101/2023.03.18.23287442
Sender, R., Fuchs, S., & Milo, R. (2016). Revised estimates for the number of human and bacteria cells in the body. PLOS Biology, 14(8), Article e1002533. https://doi.org/10.1371/journal.pbio.1002533
Wróbel-Dudzińska, D., Osial, N., Stępień, P. W., Gorecka, A., & Żarnowski, T. (2023). Prevalence of dry eye symptoms and associated risk factors among university students in Poland. International Journal of Environmental Research and Public Health, 20(2), 1313. https://doi.org/10.3390/ijerph20021313
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