Antifungal effect of Lacticaseibacillus rhamnosus GG against oral candidiasis in diabetic rats
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Abstract
Background and Objectives: Diabetes mellitus (DM) increases the risk of oral candidiasis by impairing immunity and enhancing Candida virulence. Although Lacticaseibacillus rhamnosus GG (LGG) has antifungal potential, its effect in diabetes remains unclear. This study evaluated the efficacy of LGG against C. albicans and C. tropicalis in diabetic rats.
Materials and Methods: A fungal suspension (1×10⁷ CFU/mL) was applied to the tongue for three days in the controls and experimental groups of male alloxan-induced diabetic Sprague-Dawley rats. Then, LGG (0.3 mL of 1×10⁸ CFU/mL) was administered for 28 days in the experimental groups. Weekly oral swabs were analyzed, and blood and tongue tissues were evaluated using biochemical, histopathological, and molecular methods (TLR2, TLR4, and Msp1/p75).
Results: Diabetic rats showed weight loss and increased oral Candida growth. LGG reduced C. albicans and C. tropicalis counts and stabilized body weight. Haematological and biochemical parameters improved with probiotic treatment. Histopathological examination showed reduced inflammation, and molecular analyses indicated modulation of Msp1/p75 and TLR2/TLR4. Overall, LGG provided antifungal and immunomodulatory benefits in diabetic rats with oral candidiasis.
Conclusion: This study assessed the efficacy of LGG against C. albicans and C. tropicalis in diabetic rats. Administration of LGG reduced Candida colonization and maintained normal physiological parameters. These results suggest that LGG has potential as a safe complementary antifungal therapy.
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7. AL-Ishaq RK, Samuel SM, Büsselberg D. The influence of gut microbial species on diabetes mellitus. Int J Mol Sci 2023; 24: 8118.
8. Rabiee MR, Babajafari S. Probiotics and diabetes: A review. Int J Nutr Sci 2018; 3: 73-81.
9. Mukherjee S, Karmakar S, Babu SPS. TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. Braz J Infect Dis 2016; 20: 193-204.
10. Llewellyn A, Foey A. Probiotic modulation of innate cell pathogen sensing and signaling events. Nutrients 2017; 9: 1156.
11. Gupta A, Kumar R, Pandey AK. Antioxidant and antidiabetic activities of Terminalia bellirica fruit in alloxan induced diabetic rats. S Afr J Bot 2020; 130: 308-315.
12. Ighodaro OM, Adeosun AM, Akinloye OA. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plant extracts in experimental studies. Medicina (Kaunas) 2017; 53: 365-374.
13. Amin LE. Biological assessment of ozone therapy on experimental oral candidiasis in immunosuppressed rats. Biochem Biophys Rep 2018; 15: 57-60.
14. Ernst O, Zor T. Linearization of the Bradford protein assay. J Vis Exp 2010; 1918. doi: 10.3791/1918.
15. Sampath A, Weerasekera MM, Dilhari A, Gunasekara C, Bulugahapitiya U, Fernando N, et al. Type 2 diabetes mellitus and oral Candida colonization: analysis of risk factors in a Sri Lankan cohort. Acta Odontol Scand 2019; 77: 508-516.
16. Chouhan S, Kallianpur S, Prabhu KT, Tijare M, Kasetty S, Gupta S. Candidal prevalence in diabetics and its species identification. Int J Appl Basic Med Res 2019; 9: 49-54.
17. Rajasekhar B, Gujjari A, Shankaregowda R, Durbakula K. Effect of probiotics on Candida in diabetic and nondiabetic complete denture wearers – An in vivo study. J Interdiscip Dent 2020; 10: 111-116.
18. Nouraei H, Jahromi MG, Jahromi LR, Zomorodian K, Pakshir K. Potential pathogenicity of Candida species isolated from oral cavity of patients with diabetes mellitus. Biomed Res Int 2021; 2021: 9982744.
19. Bashiru Shola O, Olatunde Olugbenga F. Hyperglycaemic Environment: Contribution to the Anaemia Associated with Diabetes Mellitus in Rats Experimentally Induced with Alloxan. Anemia 2015; 2015: 848921.
20. Al-Waili NS. Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects. J Med Food 2004; 7: 100-107.
21. Uhuo NE, Godwin OK, Alaebo OP, Ezeh HC. Haematological and biochemical parameters assessment of alloxan-induced diabetic rats treated with ethanol leaf extract of Adansonia digitata leaf. Anim Res Int 2022; 19: 4469-4477.
22. Enechi OC, Okeke ES, Arum DC, Emencheta SC. Attenuation of haematological and biochemical alterations in alloxan-induced diabetic rats using ethanol extract from Annona senegalensis Persoon (Annonaceae) leaves. Eng Proc 2023; 56: 263.
23. Otton R, Carvalho CR, Mendonça JR, Curi R. Low proliferation capacity of lymphocytes from alloxan-diabetic rats: involvement of high glucose and tyrosine phosphorylation of Shc and IRS-1. Life Sci 2002; 71: 2759-2771.
24. Nduka FO, Ogugua VN, Joshua PE, Okpachi VE, Gometi SA, Nwigwe JO. Anti-diabetic and some haematological effects of aqueous and ethanol leaf extract of Eriosema psoraleoides in alloxan-induced diabetic Wistar rats. Afr J Biotechnol 2018; 17: 1292-1298.
25. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51: 216-226.
26. Namjou A, Razavie E, Heidarian E, Yazdani N, Rafieian-Kopaei M. Effects of hirudotherapy in alloxan-induced diabetic male rats: histopathological and biochemical changes. Jundishapur J Nat Pharm Prod 2023; 18(3): e120208.
27. Itova TD, Georgieva VA. Probiotic prophylaxis of neonatal jaundice. J Biomed Clin Res 2022; 15: 158-164.
28. Li Y, Zhu J, Lin G, Gao K, Yu Y, Chen S, et al. Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats. Front Nutr 2022; 9: 993951.
29. Ghosh A, Gharti Magar D, Thapa S, Nayak N, Talwar OP. Histopathology of important fungal infections – A summary. J Pathol Nepal 2019; 9: 1490-1496.
30. Sulistyani E, Triwahyuni IE, Rahayu YC, Syafriadi M, Al-Falah HH, Ayuningtyas A. A Microbial and histological analysis of rat model of oral candidiasis. J Dentomaxillofac Sci 2023; 8: 1-5.
31. Allonsius CN, Vandenheuvel D, Oerlemans EFM, Petrova MI, Donders GGG, Cos P, et al. Inhibition of Candida albicans morphogenesis by chitinase from Lactobacillus rhamnosus GG. Sci Rep 2019; 9: 2900.
32. Furnari S, Ciantia R, Garozzo A, Furneri PM, Fuochi V. Lactobacilli-Derived MicrobeAssociated Molecular Patterns (MAMPs) in Host Immune Modulation. Biomolecules 2025; 15: 1609.
33. Rocha-Ramírez LM, Pérez-Solano RA, Castañón-Alonso SL, Moreno Guerrero SS, Ramírez Pacheco A, García Garibay M, et al. Probiotic Lactobacillus strains stimulate the inflammatory response and activate human macrophages. J Immunol Res 2017; 2017: 4607491.
34. Zangl I, Pap IJ, Aspöck C, Schüller C. The role of Lactobacillus species in the control of Candida via biotrophic interactions. Microb Cell 2019; 7: 1-14.
2. Kumar BV, Padshetty NS, Bai KY, Rao MS. Prevalence of Candida in the oral cavity of diabetic subjects. J Assoc Physicians India 2005; 53: 599-602.
3. Boahen A, Than LTL, Loke YL, Chew SY. The antibiofilm role of biotics family in vaginal fungal infections. Front Microbiol 2022; 13: 787119.
4. Rodrigues CF, Rodrigues ME, Henriques M. Candida spp. infections in patients with diabetes mellitus. J Clin Med 2019; 8: 76.
5. Vazquez-Munoz R, Dongari-Bagtzoglou A. Anticandidal Activities by Lactobacillus Species: An Update on Mechanisms of Action. Front Oral Health 2021; 2: 689382.
6. Wang W, Deng Z, Wu H, Zhao Q, Li T, Zhu W, et al. A small secreted protein triggers a TLR2/4-dependent inflammatory response during invasive Candida albicans infection. Nat Commun 2019; 10: 1015.
7. AL-Ishaq RK, Samuel SM, Büsselberg D. The influence of gut microbial species on diabetes mellitus. Int J Mol Sci 2023; 24: 8118.
8. Rabiee MR, Babajafari S. Probiotics and diabetes: A review. Int J Nutr Sci 2018; 3: 73-81.
9. Mukherjee S, Karmakar S, Babu SPS. TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. Braz J Infect Dis 2016; 20: 193-204.
10. Llewellyn A, Foey A. Probiotic modulation of innate cell pathogen sensing and signaling events. Nutrients 2017; 9: 1156.
11. Gupta A, Kumar R, Pandey AK. Antioxidant and antidiabetic activities of Terminalia bellirica fruit in alloxan induced diabetic rats. S Afr J Bot 2020; 130: 308-315.
12. Ighodaro OM, Adeosun AM, Akinloye OA. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plant extracts in experimental studies. Medicina (Kaunas) 2017; 53: 365-374.
13. Amin LE. Biological assessment of ozone therapy on experimental oral candidiasis in immunosuppressed rats. Biochem Biophys Rep 2018; 15: 57-60.
14. Ernst O, Zor T. Linearization of the Bradford protein assay. J Vis Exp 2010; 1918. doi: 10.3791/1918.
15. Sampath A, Weerasekera MM, Dilhari A, Gunasekara C, Bulugahapitiya U, Fernando N, et al. Type 2 diabetes mellitus and oral Candida colonization: analysis of risk factors in a Sri Lankan cohort. Acta Odontol Scand 2019; 77: 508-516.
16. Chouhan S, Kallianpur S, Prabhu KT, Tijare M, Kasetty S, Gupta S. Candidal prevalence in diabetics and its species identification. Int J Appl Basic Med Res 2019; 9: 49-54.
17. Rajasekhar B, Gujjari A, Shankaregowda R, Durbakula K. Effect of probiotics on Candida in diabetic and nondiabetic complete denture wearers – An in vivo study. J Interdiscip Dent 2020; 10: 111-116.
18. Nouraei H, Jahromi MG, Jahromi LR, Zomorodian K, Pakshir K. Potential pathogenicity of Candida species isolated from oral cavity of patients with diabetes mellitus. Biomed Res Int 2021; 2021: 9982744.
19. Bashiru Shola O, Olatunde Olugbenga F. Hyperglycaemic Environment: Contribution to the Anaemia Associated with Diabetes Mellitus in Rats Experimentally Induced with Alloxan. Anemia 2015; 2015: 848921.
20. Al-Waili NS. Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects. J Med Food 2004; 7: 100-107.
21. Uhuo NE, Godwin OK, Alaebo OP, Ezeh HC. Haematological and biochemical parameters assessment of alloxan-induced diabetic rats treated with ethanol leaf extract of Adansonia digitata leaf. Anim Res Int 2022; 19: 4469-4477.
22. Enechi OC, Okeke ES, Arum DC, Emencheta SC. Attenuation of haematological and biochemical alterations in alloxan-induced diabetic rats using ethanol extract from Annona senegalensis Persoon (Annonaceae) leaves. Eng Proc 2023; 56: 263.
23. Otton R, Carvalho CR, Mendonça JR, Curi R. Low proliferation capacity of lymphocytes from alloxan-diabetic rats: involvement of high glucose and tyrosine phosphorylation of Shc and IRS-1. Life Sci 2002; 71: 2759-2771.
24. Nduka FO, Ogugua VN, Joshua PE, Okpachi VE, Gometi SA, Nwigwe JO. Anti-diabetic and some haematological effects of aqueous and ethanol leaf extract of Eriosema psoraleoides in alloxan-induced diabetic Wistar rats. Afr J Biotechnol 2018; 17: 1292-1298.
25. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51: 216-226.
26. Namjou A, Razavie E, Heidarian E, Yazdani N, Rafieian-Kopaei M. Effects of hirudotherapy in alloxan-induced diabetic male rats: histopathological and biochemical changes. Jundishapur J Nat Pharm Prod 2023; 18(3): e120208.
27. Itova TD, Georgieva VA. Probiotic prophylaxis of neonatal jaundice. J Biomed Clin Res 2022; 15: 158-164.
28. Li Y, Zhu J, Lin G, Gao K, Yu Y, Chen S, et al. Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats. Front Nutr 2022; 9: 993951.
29. Ghosh A, Gharti Magar D, Thapa S, Nayak N, Talwar OP. Histopathology of important fungal infections – A summary. J Pathol Nepal 2019; 9: 1490-1496.
30. Sulistyani E, Triwahyuni IE, Rahayu YC, Syafriadi M, Al-Falah HH, Ayuningtyas A. A Microbial and histological analysis of rat model of oral candidiasis. J Dentomaxillofac Sci 2023; 8: 1-5.
31. Allonsius CN, Vandenheuvel D, Oerlemans EFM, Petrova MI, Donders GGG, Cos P, et al. Inhibition of Candida albicans morphogenesis by chitinase from Lactobacillus rhamnosus GG. Sci Rep 2019; 9: 2900.
32. Furnari S, Ciantia R, Garozzo A, Furneri PM, Fuochi V. Lactobacilli-Derived MicrobeAssociated Molecular Patterns (MAMPs) in Host Immune Modulation. Biomolecules 2025; 15: 1609.
33. Rocha-Ramírez LM, Pérez-Solano RA, Castañón-Alonso SL, Moreno Guerrero SS, Ramírez Pacheco A, García Garibay M, et al. Probiotic Lactobacillus strains stimulate the inflammatory response and activate human macrophages. J Immunol Res 2017; 2017: 4607491.
34. Zangl I, Pap IJ, Aspöck C, Schüller C. The role of Lactobacillus species in the control of Candida via biotrophic interactions. Microb Cell 2019; 7: 1-14.
| Files | ||
| Issue | Vol 18 No 4 (2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Candida albicans Candida tropicalis Lacticaseibacillus rhamnosus Probiotics Toll-like receptors | ||
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How to Cite
1.
Kanthi Vaishnavi V, Banik U, Chuah C, Parasuraman S. Antifungal effect of Lacticaseibacillus rhamnosus GG against oral candidiasis in diabetic rats. Iran J Microbiol. 2026;18(4):595-606.
