Lacticaseibacillus rhamnosus Probiotics Improve Fasting Blood Glucose, HOMA-IR, and Reduce Body Weight in Diabetic Rat Model
Abstract
BACKGROUND: Indonesian indigenous probiotics have been found to improve disruptions of tight junctions in the intestinal epithelium and reduce total cholesterol levels. Improvement in the tight junction could decrease the LPS level and further reduce the blood glucose and insulin resistance. The effects of indigenous Indonesian Lacticaseibacillus rhamnosus (Lr) probiotics on glucose metabolism and inflammatory marker levels in diabetic rats was studied to find if these probiotics are suitable as potential supplementation treatment in diabetes.
METHODS: Sixteen female Wistar rats were induced with diabetes using streptozotocin and fed a high-fat, high-sucrose diet. The rats were separated into four groups: LrFBB81, LrFSMM22, LrSKG34, and a control group. Each intervention group got daily dosages of 1 mL probiotic suspensions containing 109 CFU/mL cells given orally for 14 days, whereas the control group received saline. Fasting blood glucose (FBG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), lipopolysaccharide (LPS), and body weight were evaluated.
RESULTS: FBG was significantly reduced in LrFSMM22 group (Δ=120.75 mg/dL, p=0.035), while significant reduction was not observed from LrFBB81, LrSKG34, and control groups. No statistically significant differences were found in HOMA-IR before and after intervention in all groups, but Δ HOMA-IR from LrFSMM22 group was reduced more than the control group (-3.90 vs. 2.02, p=0.028). All groups showed no significant differences in LPS level, meanwhile statistically significant reduction in body weight was observed in all probiotic groups, LrFBB81 (Δ=-15.7 gram, p=0.040), LrSKG34 (Δ= -20.43 gram, p=0.006), and LrFSMM22 groups (Δ=-18.33 gram, p=0.037).
CONCLUSION: The administration of L. rhamnosus could improve FBG, HOMA-IR, and reduce body weight without suppressing the LPS.
KEYWORDS: diabetes, probiotic, Lacticaseibacillus rhamnosus, fasting blood glucose, HOMA-IR, lipopolysaccharide, insulin resistance
Full Text:
PDFReferences
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020; 21(17): 6275, CrossRef.
Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. 9th edition. Diabetes Res Clin Pract. 2019; 157: 107843, CrossRef.
Demir S, Nawroth PP, Herzig S, Ekim Üstünel B. Emerging targets in type 2 diabetes and diabetic complications. Adv Sci. 2021; 8(18): e2100275, CrossRef.
Xia F, Wen LP, Ge BC, Li YX, Li FP, Zhou BJ. Gut microbiota as a target for prevention and treatment of type 2 diabetes: Mechanisms and dietary natural products. World J Diabetes. 2021; 12(8): 1146-63, CrossRef.
Gomes AC, Bueno AA, de Souza RG, Mota JF. Gut microbiota, probiotics and diabetes. Nutr J. 2014; 13: 60, CrossRef.
Larsen N, Vogensen FK, Van Den Berg FWJ, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE. 2010; 5(2): e9085, CrossRef.
O'Mahony D, Murphy S, Boileau T, Park J, O'Brien F, Groeger D, et al. Bifidobacterium animalis AHC7 protects against pathogen-induced NF-κB activation in vivo. BMC Immunol. 2010; 11: 63, CrossRef.
Kuang YS, Lu JH, Li SH, Li JH, Yuan MY, He JR, et al. Connections between the human gut microbiome and gestational diabetes mellitus. Gigascience. 2017; 6(8): 1-12, CrossRef.
Chaiyasut C, Sivamaruthi BS, Lailerd N, Sirilun S, Khongtan S, Fukngoen P, et al. Probiotics supplementation improves intestinal permeability, obesity index and metabolic biomarkers in elderly Thai subjects: A randomized controlled trial. Foods. 2022; 11(3): 268, CrossRef.
Fatmawati NND, Gotoh K, Mayura IPB, Nocianitri KA, Ramona Y, Sakaguchi M, et al. Caco-2 cells monolayer as an in-vitro model for probiotic strain translocation. Bali Med J. 2020; 1: 137-42, CrossRef.
Sujaya IN, Sukrama IDM, Komang Ayu N, Yan R, Wayan Redi A, Pratiwi IDPK. Efek konsumsi bio-yoghurt dari Lactobacillus rhamnosus SKG34 terhadap lipid profile pada manusia. Arc Com. Health. 2013; 2(1): 40-9, article.
Nocianitri KA, Sujaya IN, Ramona Y. Probiotic microcapsul of Lactobacillus rhamnosus FBB81 and its viability during storage. Sci J Food Technol. 2020; 6: 76-82, article.
Fatmawati NND, Gotoh K, Mayura IPB, Nocianitri KA, Suwardana GNR, Komalasari N, et al. Enhancement of intestinal epithelial barrier function by Weissella confusa F213 and Lactobacillus rhamnosus FBB81 probiotic candidates in an in vitro model of hydrogen peroxide-induced inflammatory bowel disease. BMC Res Notes. 2020; 13(1): 489, CrossRef.
Shi T, Nishiyama K, Nakamata K, Aryantini NPD, Mikumo D, Oda Y, et al. Isolation of potential probiotic Lactobacillus rhamnosus strains from traditional fermented mare milk produced in Sumbawa island of Indonesia. Biosci Biotechnol Biochem. 2012; 76(10): 1897-903, CrossRef.
Aryantini NPD, Kondoh D, Nishiyama K, Yamamoto Y, Mukai T, Sujaya IN, et al. Anchorless cell surface proteins function as laminin-binding adhesins in Lactobacillus rhamnosus FSMM22. FEMS Microbiol Lett. 2017; 364(6): fnx056, CrossRef.
Nishiyama K, Nakamata K, Ueno S, Terao A, Aryantini NPD, Sujaya IN, et al. Adhesion properties of Lactobacillus rhamnosus mucus-binding factor to mucin and extracellular matrix proteins. Biosci Biotechnol Biochem. 2015; 79(2): 271-9, CrossRef.
Sujaya IN, Utami DNM, Suariani NLP, Widarini NP, Nocianitri KA, Nursini NW. Probiotic potency of Lactobacillus spp. isolated from Sumbawa mare milk. JVeteriner. 2008; 9: 33-40, article.
Nocianitri K, Antara N, Sugitha IM, Sukrama D, Ramona Y, Sujaya IN. The effect of two Lactobacillus rhamnosus strains on the blood lipid profile of rats fed with high fat containing diet. Int Food Res J. 2017; 24: 795-802, article.
Park KY, Kim B, Hyun CK. Lactobacillus rhamnosus GG reverses insulin resistance but does not block its onset in diet-induced obese mice. J Microbiol Biotechnol. 2015; 25(5): 753-7, CrossRef.
Fachrial E, Lina J, Harmileni H, Anggraini S, Sihotang W. Hypoglycemic activity and safety assessment of Pediococcus acidilactici strain DNH16 in experimental type 2 diabetes mellitus rats induced with streptozotocin. Indones Biomed J. 2024; 16(1): 31-9, CrossRef.
Han M, Liao W, Dong Y, Bai C, Gai Z. Lacticaseibacillus rhamnosus Hao9 exerts antidiabetic effects by regulating gut microbiome, glucagon metabolism, and insulin levels in type 2 diabetic mice. Front Nutr. 2022; 9: 1081778, CrossRef.
Honda K, Moto M, Uchida N, He F, Hashizume N. Anti-diabetic effects of lactic acid bacteria in normal and type 2 diabetic mice. J Clin Biochem Nutr. 2012; 51(2): 96-101, CrossRef.
Choi SI, You S, Kim S, Won G, Kang CH, Kim GH. Weissella cibaria MG5285 and Lactobacillus reuteri MG5149 attenuated fat accumulation in adipose and hepatic steatosis in high-fat diet-induced C57BL/6J obese mice. Food Nutr Res. 2021; 65::10.29219/fnr.v65.8087, CrossRef.
Salles BIM, Cioffi D, Ferreira SRG. Probiotics supplementation and insulin resistance: A systematic review. Diabetol Metab Syndr. 2020; 12(1): 98, CrossRef.
Velayati A, Kareem I, Sedaghat M, Sohrab G, Nikpayam O, Hedayati M, et al. Does symbiotic supplementation which contains Bacillus Coagulans Lactobacillus rhamnosus, Lactobacillus acidophilus and fructooligosaccharide has favourite effects in patients with type-2 diabetes? A randomised, double-blind, placebo-controlled trial. Arch Physiol Biochem. 2023; 129(6): 1211-8, CrossRef.
Zhang J, Wang S, Zeng Z, Qin Y, Shen Q, Li P. Anti-diabetic effects of Bifidobacterium animalis 01 through improving hepatic insulin sensitivity in type 2 diabetic rat model. J Funct Foods. 2020; 67: 103843, CrossRef.
Colletti A, Pellizzato M, Cicero AF. The possible role of probiotic supplementation in inflammation: A narrative review. Microorganisms. 2023; 11(9): 2160, CrossRef.
Sariyanti M, Andita T, Erlinawati N, Yunita E, Nasution A, Sari K, et al. Probiotic Lactobacillus acidophilus FNCC 0051 improves pancreatic histopathology in streptozotocin-induced type-1 diabetes mellitus rats. Indones Biomed J. 2022; 14(4): 329-441, CrossRef.
Yu HS, Lee NK, Choi AJ, Choe JS, Bae CH, Paik HD. Anti-inflammatory potential of probiotic strain Weissella cibaria JW15 isolated from kimchi through regulation of NF-κB and MAPKs pathways in LPS-induced RAW 264.7 cells. J Microbiol Biotechnol. 2019; 29(7): 1022-32, CrossRef.
Zhou J, Martin RJ, Raggio AM, Shen L, McCutcheon K, Keenan MJ. The importance of GLP-1 and PYY in resistant starch's effect on body fat in mice. Mol Nutr Food Res. 2015; 59(5): 1000-3, CrossRef.
Hasain Z, Mokhtar NM, Kamaruddin NA, Mohamed Ismail NA, Razalli NH, Gnanou JV, et al. Gut microbiota and gestational diabetes mellitus: A review of host-gut microbiota interactions and their therapeutic potential. Front Cell Infect Microbiol. 2020; 10: 188, CrossRef.
Marathe CS, Rayner CK, Jones KL, Horowitz M. Glucagon-like peptides 1 and 2 in health and disease: A review. Peptides. 2013; 44: 75-86, CrossRef.
Fontana L, Plaza-Díaz J, Robles-Bolívar P, Valente-Godínez H, Sáez-Lara MJ, Abadía-Molina F, et al. Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 modulate macrophage gene expression and ameliorate damage markers in the liver of Zucker-Lepr (fa/fa) rats. Nutrients. 2021; 13(1): 202, CrossRef.
Ritze Y, Bárdos G, Claus A, Ehrmann V, Bergheim I, Schwiertz A, et al. Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice. PLoS One. 2014; 9(1): e80169, CrossRef.
Gorman A, Golovanov AP. Lipopolysaccharide structure and the phenomenon of low endotoxin recovery. Eur J Pharm. Biopharm. 2022; 180: 289-307, CrossRef.
Zhang X, Jiang L, Xie C, Mo Y, Zhang Z, Xu S, et al. The recombinant Lactobacillus strains with the surface-displayed expression of Amuc_1100 ameliorate obesity in high-fat diet-fed adult mice. Bioengineering. 2024; 11(6): 574, CrossRef.
Crovesy L, Ostrowski M, Ferreira D, Rosado EL, Soares-Mota M. Effect of Lactobacillus on body weight and body fat in overweight subjects: A systematic review of randomized controlled clinical trials. Int J Obes. 2017; 41(11): 1607-14, CrossRef.
Ma Y, Fei Y, Han X, Liu G, Fang J. Lactobacillus plantarum alleviates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice. Front Nutr. 2022; 9: 947367, CrossRef.
DOI: https://doi.org/10.18585/inabj.v17i1.3525
Copyright (c) 2025 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
