EFFICACY EVALUATION OF PROBIOTIC LACTOBACILLUS RHAMNOSUS SUSPENSION FORMULATED WITH MEDIUM CHAIN TRIGLYCERIDES OIL IN DNBS-INDUCED COLITIS IN SPRAGUE-DAWLEY RATS

Authors

  • Dharmeshkumar B. Kheni Kadi Sarva Vishwavidyalaya, Gandhinagar, Gujarat, India
  • Varun P. Sureja Kadi Sarva Vishwavidyalaya, Gandhinagar, Gujarat, India
  • Shrikalp S. Deshpande K.B. Institute of Pharmaceutical Education and Research, Affiliated to Kadi Sarva Vishwavidyalaya, Gandhinagar, Gujarat, India
  • Vishal P. Dubey Sundyota Numandis Probioceuticals Pvt. Ltd., Ahmedabad, Gujarat, India
  • Jignesh J. Kansagra Sundyota Numandis Probioceuticals Pvt. Ltd., Ahmedabad, Gujarat, India
  • Aditi H. Bariya Arihant School of Pharmacy & Bio-Research, Ahmedabad, Gujarat, India

Abstract

Inflammatory bowel disease (IBD) is a highly prevalent chronic inflammatory disease condition leading to widespread gastrointestinal tract (GIT) damage. Based on the severity, the symptoms of IBD vary ranging from mild and frequent abdominal pain, bloating, and diarrhea to severe bloody stools, anemia, unconsciousness, and sometimes fatal as well. Gut dysbiosis is found to play one of the major roles in the pathogenesis of IBD. The current study aimed to evaluate the effectiveness of a probiotic (Lactobacillus rhamnosus) suspension in medium-chain triglycerides (MCT) oil against dinitrobenzene sulfonic acid (DNBS) induced colitis in rats. Colitis was induced in Sprague Dawley (SD) rats by intra-rectal administration of DNBS (120 mg/kg/rat) followed by 3 days of colitis induction. Following colitis induction, rats were evenly randomized to receive either dexamethasone (2 mg/kg/day orally) or L. rhamnosus oil suspension (3 x 106 CFU/g/day orally) for 28 consecutive days. The body weight, average food, and water intake, histological analysis, colon weight, biomarkers of oxidative stress (nitric oxide (NO) and malondialdehyde (MDA)), intestinal inflammation (fecal calprotectin), and antioxidant potential (glutathione (GSH) and superoxide dismutase (SOD)). The level of colonic damage was evaluated using the colonic mucosal damage index (CMDI) and disease activity index (DAI) scores. GraphPad Prism software was used for statistical analysis with p < 0.05 as the significance threshold. Dexamethasone and L. rhamnosus oil suspension significantly prevented body weight and food and water intake reduction. Similarly, dexamethasone and L. rhamnosus oil suspension therapy significantly attenuated the DNBS-induced colonic damage level. This effect was accompanied by significant improvement in the antioxidant biomarker levels (GSH and SOD) and reduction in the oxidative stress and intestinal inflammation level. In all the evaluated parameters, dexamethasone therapy significantly better than the L. rhamnosus oil suspension therapy. The results of this study highlight the protective effect of dexamethasone and L. rhamnosus oil suspension therapy in a DNBS-induced experimental colitis model, an effect that might be attributed to the therapies' antioxidant and anti-inflammatory potential.

Keywords:

Probiotic, Lactobacillus rhamnosus, Dexamethasone, Inflammatory bowel disease, Oxidative stress, Inflammation, Gut dysbiosis

DOI

https://doi.org/10.25004/IJPSDR.2025.170209

References

Ramos GP, Papadakis KA. Mechanisms of Disease: Inflammatory Bowel Diseases. Mayo Clinic Proceedings. 2019;94(1):155–165. Available from: doi.org/10.1016/j.mayocp.2018.09.013.

Zhang YZ, Li YY. Inflammatory bowel disease: Pathogenesis. World Journal of Gastroenterology. 2014;20(1):91-99. Available from: doi.org/10.3748/wjg.v20.i1.91.

Vermeire S, Van Assche G, Rutgeerts P. Classification of inflammatory bowel disease: the old and the new. Current opinion in gastroenterology. 2012;28(4):321–326. Available from: doi.org/10.1097/MOG.0b013e328354be1e.

Ray G. Inflammatory bowel disease in India - Past, present and future. World Journal of Gastroenterology. 2016;22(36):8123–8136. Available from: doi.org/10.3748/wjg.v22.i36.8123.

Kedia S, Ahuja V. Epidemiology of Inflammatory Bowel Disease in India: The Great Shift East. Inflammatory Intestinal Diseases. 2017;2(2):102–115. Available from: doi.org/10.1159/000465522.

Dam AN, Berg AM, Farraye FA. Environmental Influences on the Onset and Clinical Course of Crohn’s Disease—Part 1: An Overview of External Risk Factors. Gastroenterology & Hepatology. 2013;9(11):711-717.

Davis J, Kellerman R. Gastrointestinal Conditions: Inflammatory Bowel Disease. FP essentials. 2022;516:23–30.

Singh S, Blanchard A, Walker JR, Graff LA, Miller N, Bernstein CN. Common Symptoms and Stressors Among Individuals With Inflammatory Bowel Diseases. Clinical Gastroenterology and Hepatology. 2011;9(9):769–775. Available from: doi.org/10.1016/j.cgh.2011.05.016.

Linschoten RCA, Visser E, Niehot CD, Woude CJ, Hazelzet JA, Noord D, et al. Systematic review: societal cost of illness of inflammatory bowel disease is increasing due to biologics and varies between continents. Alimentary Pharmacology & Therapeutics. 2021;54(3):234–248. Available from: doi.org/10.1111/apt.16445.

Coward S, Windsor J, Benchimol E, Bernstein C, Avina-Zubieta A, Bitton A, et al. THE COST OF INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED ANALYSIS OF ADMINISTRATIVE DATA. Inflammatory Bowel Diseases. 2024;30(Supplement_1):S40. Available from: doi.org/10.1093/ibd/izae020.084.

Duff W, Haskey N, Potter G, Alcorn J, Hunter P, Fowler S. Non-pharmacological Therapies for Inflammatory Bowel disease: Recommendations for self-care and Physician Guidance. World Journal of Gastroenterology.2018;24(28):3055–3070. Available from: doi.org/10.3748/wjg.v24.i28.3055.

Leitner GC. Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World Journal of Gastrointestinal Pharmacology and Therapeutics. 2016;7(1):5-20. Available from: doi.org/10.4292/wjgpt.v7.i1.5.

Kheni DB, Sureja VP, Deshpande SS, Dubey VP, Kansagra JJ. A Systematic Mapping Review of In-Vitro and In-Vivo Evidences Exploring The Role of Strain-Specific Probiotic Bifidobacterium longum W11: International Journal of Pharmaceutical Sciences and Drug Research.2024;127–134. Available from: doi.org/10.25004/IJPSDR.2024.160117

Jandhyala SM. Role of the Normal Gut Microbiota. World Journal of Gastroenterology. 2015;21(29):8787- 8803. Available from: doi.org/10.3748/wjg.v21.i29.8787

Bidell MR, Hobbs ALV, Lodise TP. Gut microbiome health and dysbiosis: A clinical primer. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2022;42(11):849–857. Available from: doi.org/10.1002/phar.2731

Santana PT, Rosas SLB, Ribeiro BE, Marinho Y, de Souza HSP. Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets. International Journal of Molecular Sciences. 2022;23(7):3464. Available from: doi.org/10.3390/ijms23073464

Ram Hari Dahal, Kim S, Yu Kyung Kim, Eun Soo Kim, Kim J. Insight into gut dysbiosis of patients with inflammatory bowel disease and ischemic colitis. Frontiers in Microbiology. 2023; 14:1174832. Available from: doi.org/10.3389/fmicb.2023.1174832

Shan Y, Lee M, Chang EB. The Gut Microbiome and Inflammatory Bowel Diseases. Annual Review of Medicine. 2022;73:455–468. Available from: doi.org/10.1146/annurev-med-042320-021020.

Lal S, Kandiyal B, Ahuja V, Takeda K, Das B. Gut microbiome dysbiosis in inflammatory bowel disease. Progress in Molecular Biology and Translational Science.2022;192(1):179-204. Available from: doi.org/10.1016/bs.pmbts.2022.09.003

Fijan S. Microorganisms with Claimed Probiotic Properties: An Overview of Recent Literature. International Journal of Environmental Research and Public Health. 2014;11(5):4745–4767. Available from: doi.org/10.3390/ijerph110504745

Ma T, Shen X, Shi X, Sakandar HA, Quan K, Li Y, et al. Targeting gut microbiota and metabolism as the major probiotic mechanism - An evidence-based review. Trends in Food Science & Technology. 2023;138:178–198. Available from: doi.org/10.1016/j.tifs.2023.06.013

Chandrasekaran P, Weiskirchen S, Ralf Weiskirchen. Effects of Probiotics on Gut Microbiota: An Overview. International journal of molecular sciences. 2024;25(11):6022. Available from: doi.org/10.3390/ijms25116022

Li C, Niu Z, Zou M, Liu S, Wang M, Gu X, et al. Probiotics, prebiotics, and synbiotics regulate the intestinal microbiota differentially and restore the relative abundance of specific gut microorganisms. Journal of Dairy Science. 2020;103(7):5816–5829. Available from: doi.org/10.3168/jds.2019-18003

Ahn SI, Cho S, Choi NJ. Effect of dietary probiotics on colon length in an inflammatory bowel disease-induced murine model: A meta-analysis. Journal of dairy science. 2020;103(2):1807–1819. Available from: doi.org/10.3168/jds.2019-17356

Zhang T, Zhang J, Duan L. The Role of Genetically Engineered Probiotics for Treatment of Inflammatory Bowel Disease: A Systematic Review. Nutrients. 2023;15(7):1566. Available from: doi.org/10.3390/nu15071566

Huang Y, Peng S, Zeng R, Yao H, Feng G, Fang J. From probiotic chassis to modification strategies, control and improvement of genetically engineered probiotics for inflammatory bowel disease. Microbiological Research. 2024;289:127928. Available from: doi.org/10.1016/j.micres.2024.127928

Pesce M, Seguella L, Del Re A, Lu J, Palenca I, Corpetti C, et al. Next-Generation Probiotics for Inflammatory Bowel Disease. International Journal of Molecular Sciences.2022;23(10):5466. Available from: doi.org/10.3390/ijms23105466.

Khafipour A, Eissa N, Munyaka PM, Rabbi MF, Kapoor K, Kermarrec L, et al. Denosumab Regulates Gut Microbiota Composition and Cytokines in Dinitrobenzene Sulfonic Acid (DNBS)-Experimental Colitis. Frontiers in Microbiology. 2020;11:1405. Available from: doi.org/10.3389/fmicb.2020.01405.

Zhou Y, Xu H, Xu J, Guo X, Zhao H, Chen Y, et al. F. prausnitzii and its supernatant increase SCFAs-producing bacteria to restore gut dysbiosis in TNBS-induced colitis. AMB Express. 2021;11(1):33. Available from: doi.org/10.1186/s13568-021-01197-6.

Son M, Park IS, Kim S, Ma HW, Kim JH, Kim TI, et al. Novel Potassium-Competitive Acid Blocker, Tegoprazan, Protects Against Colitis by Improving Gut Barrier Function. Frontiers in Immunology. 2022:13:870817. Available from: doi.org/10.3389/fimmu.2022.870817.

Maciel-Fiuza MF, Muller GC, Campos DMS, do Socorro Silva Costa P, Peruzzo J, Bonamigo RR, et al. Role of gut microbiota in infectious and inflammatory diseases. Frontiers in Microbiology. 2023;14:1098386. Available from: doi.org/10.3389/fmicb.2023.1098386.

Valdes AM, Walter J, Segal E, Spector TD. Role of the Gut Microbiota in Nutrition and Health. British Medical Journal. 2018; 361:k2179. Available from: doi.org/10.1136/bmj.k2179.

Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therapeutic Advances in Gastroenterology. 2013;6(1):39–51. Available from: doi.org/10.1177/1756283X12459294.

Muro P, Zhang L, Li S, Zhao Z, Jin T, Mao F, et al. The emerging role of oxidative stress in inflammatory bowel disease. Frontiers in Endocrinology. 2024;15:1390351. Available from: doi.org/10.3389/fendo.2024.1390351.

Liu P, Li Y, Wang R, Ren F, Wang X. Oxidative Stress and Antioxidant Nanotherapeutic Approaches for Inflammatory Bowel Disease. Biomedicines. 2021;10(1):85. Available from: doi.org/10.3390/biomedicines10010085.

Morgan MJ, Liu Z. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Research. 2011;21(1):103–115. Available from: doi.org/10.1038/cr.2010.178.

Khansari N, Shakiba Y, Mahmoudi M. Chronic Inflammation and Oxidative Stress as a Major Cause of Age- Related Diseases and Cancer. Recent Patents on Inflammation & Allergy Drug Discovery. 2009;3(1):73–80. Available from: doi.org/10.2174/187221309787158371.

Ramos-González EJ, Bitzer-Quintero OK, Ortiz G, Hernández-Cruz JJ, Ramírez-Jirano LJ. Relationship between inflammation and oxidative stress and its effect on multiple sclerosis. Neurología. 2024;39(3): :292-301. Available from: doi.org/10.1016/j.nrleng.2021.10.010.

Tian T, Wang Z, Zhang J. Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies. Oxidative Medicine and Cellular Longevity. 2017:2017:4535194. Available from: doi.org/10.1155/2017/4535194.

Hamid Mostafavi Abdolmaleky, Zhou JR. Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases. Antioxidants.2024;13(8):985. Available from: doi.org/10.3390/antiox13080985.

Li L, Peng P, Ding N, Jia W, Huang C, Tang Y. Oxidative Stress, Inflammation, Gut Dysbiosis: What Can Polyphenols Do in Inflammatory Bowel Disease? Antioxidants. 2023;12(4):967. Available from: doi.org/10.3390/antiox12040967.

Li Q, Zheng T, Ding H, Chen J, Li B, Zhang Q, et al. Exploring the Benefits of Probiotics in Gut Inflammation and Diarrhea—From an Antioxidant Perspective. Antioxidants. 2023 ;12(7):1342. Available from: doi.org/10.3390/antiox12071342.

Ballini A, Santacroce L, Cantore S, Bottalico L, Dipalma G, Topi S, et al. Probiotics Efficacy on Oxidative Stress Values in Inflammatory Bowel Disease: A Randomized Double-Blinded Placebo-Controlled Pilot Study. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2019;19(3):373–81. Available from: doi.org/10.2174/1871530319666181221150352.

Nesina Avdagić, Asija Zaciragic, Nermina Babić, Mirsada Hukić, Seremet M, Orhan Lepara, et al. Nitric oxide as a potential biomarker in inflammatory bowel disease. Bosnian Journal of Basic Medical Sciences.2013;13(1):5–9. Available from: doi.org/10.17305/bjbms.2013.2402.

Byndloss MX, Olsan EE, Rivera-Chávez F, Tiffany CR, Cevallos SA, Lokken KL, et al. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science. 2017;357(6351):570–575. Available from: doi.org/10.1126/science.aam9949.

Cordiano R, Di Gioacchino M, Mangifesta R, Panzera C, Gangemi S, Minciullo PL. Malondialdehyde as a Potential Oxidative Stress Marker for Allergy-Oriented Diseases: An Update. Molecules.2023;28(16):5979. Available from: doi.org/10.3390/molecules28165979.

Aquilano K, Baldelli S, Ciriolo MR. Glutathione: new roles in redox signaling for an old antioxidant. Frontiers in Pharmacology. 2014;5:196. Available from: doi.org/10.3389/fphar.2014.00196.

Younus H. Therapeutic potentials of superoxide dismutase. International Journal of Health Sciences.2018;12(3):88–93.

Korczowska-Łącka I, Słowikowski B, Piekut T, Hurła M, Banaszek N, Szymanowicz O, et al. Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases. Antioxidants. 2023;12(10):1811. Available from: doi.org/10.3390/antiox12101811.

Lee S, Hu L. Nrf2 activation through the inhibition of Keap1–Nrf2 protein–protein interaction. Medicinal Chemistry Research.2020;29(5):846-867. Available from: doi.org/10.1007/s00044-020-02539-y.

Moura FA, de Andrade KQ, dos Santos JCF, Araújo ORP, Goulart MOF. Antioxidant therapy for treatment of inflammatory bowel disease: Does it work? Redox Biology. 2015;6:617–639. Available from: doi.org/10.1016/j.redox.2015.10.006.

Wang Y, Wu Y, Wang Y, Xu H, Mei X, Yu D, et al. Antioxidant Properties of Probiotic Bacteria. Nutrients. 2017;19;9(5):521. Available from: doi.org/10.3390/nu9050521.

Pathirana WGW, Chubb SP, Gillett MJ, Vasikaran SD. Faecal Calprotectin. The Clinical Biochemist Reviews. 2018;39(3):77–90.

Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body. Frontiers in Immunology.2021;12:578386. Available from: doi.org/10.3389/fimmu.2021.578386.

Published

30-03-2025
Statistics
Abstract Display: 90
PDF Downloads: 69
Dimension Badge

How to Cite

“EFFICACY EVALUATION OF PROBIOTIC LACTOBACILLUS RHAMNOSUS SUSPENSION FORMULATED WITH MEDIUM CHAIN TRIGLYCERIDES OIL IN DNBS-INDUCED COLITIS IN SPRAGUE-DAWLEY RATS”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 17, no. 2, Mar. 2025, pp. 185-93, https://doi.org/10.25004/IJPSDR.2025.170209.

Issue

Section

Research Article

How to Cite

“EFFICACY EVALUATION OF PROBIOTIC LACTOBACILLUS RHAMNOSUS SUSPENSION FORMULATED WITH MEDIUM CHAIN TRIGLYCERIDES OIL IN DNBS-INDUCED COLITIS IN SPRAGUE-DAWLEY RATS”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 17, no. 2, Mar. 2025, pp. 185-93, https://doi.org/10.25004/IJPSDR.2025.170209.

Similar Articles

1-10 of 316

You may also start an advanced similarity search for this article.