Novel 3-strain Combinatorial Probiotics Alleviates Symptoms of Inflammatory Bowel Disease in Mice
Shinjini Mitra and Ena Ray Banerjee*
Immunology and Regenerative Medicine Research Laboratory, Department of Zoology, University of Calcutta, Kolkata, India
*Corresponding Author: Ena Ray Banerjee, Professor, Immunology and Regenerative Medicine Research Laboratory, Department of Zoology, University of Calcutta, Kolkata, India.
Received:
May 06, 2022; Published: June 06, 2022
Abstract
Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, with no permanent and safe cure. We designed this study, using a 3-strain novel combinatorial probiotic formulation (ABT) as therapy for IBD. The anti-inflammatory, pro-regenerative, and antibacterial activities of ABT were determined in vitro, and then validated in mice with IBD.
The anti-inflammatory activity of ABT on DSS-treated RAW cells was determined by MTT and NBT assays, and its antibacterial effect was determined against pathogenic bacteria. ABT was administered orally on days 5, 7, 9, 11 and 13, to mice with DSS-induced IBD. After sacrifice on day 14, disease parameters were measured.
ABT showed significant anti-inflammatory and pro-regenerative effects for over 96 hours, and inhibited 4 pathogenic bacterial strains. In mice, ABT successfully reduced symptoms of IBD, evidenced by restoration in body weight, cellular status, tissue structure, and mediators.
We inferred that the individual strains contributed cumulatively to the biological activities of ABT. The bacteria in the ABT adhered to the intestinal epithelium, and initiated repair mechanisms, by downregulating mediators (NFκB, TNFα, IL-1β, NO, and IAP), and upregulating mucus production. Thus, this translationally-valuable novel combination can be an economical and safe therapy for IBD.
Keywords: Combinatorial Probiotics; GRAS; Anti-inflammatory; Antibacterial; Adherence; Pro-regenerative
References
- National Institutes of Health (NIH), USA. Probiotics: What You Need To Know. National Center for Complementary and Integrative Health (2019).
- de Vrese M and Schrezenmeir J. “Probiotics, prebiotics, and synbiotics”. Advances in Biochemical Engineering/Biotechnology 111 (2008): 1-66.
- Fijan S. “Microorganisms with Claimed Probiotic Properties: An Overview of Recent Literature”. International Journal of Environmental Research and Public Health 5 (2014): 4745-4767.
- Singhi SC and Kumar S. “Probiotics in critically ill children”. F1000 Research (Review) 5 (2016): 407.
- Stavropoulou E and Bezirtzoglou E. “Probiotics in Medicine: A Long Debate”. Frontiers in Immunology 11 (2020): 2192.
- Doron S and Snydman DR. “Risk and safety of probiotics”. Clinical Infectious Disease (Review) 60 (2015): S129-34.
- Probiotic Association of India (https://www.probioticindia.com/2011-11-12-13-28-20/probioics-products).
- Gopal PK. “Lactobacillus spp.: Lactobacillus acidophilus”. In Encyclopedia of Dairy Sciences (2nd) (2011): 91-95.
- Mitsuoka T. “Bifidobacteria and their role in human health”. Journal of Industrial Microbiology 6 (1990): 263-267.
- Turroni F., et al. “Bifidobacterium bifidum: A Key Member of the Early Human Gut Microbiota”. Microorganisms 11 (2019): 544.
- Harnett J., et al. “Lactic Acid Bacteria | Streptococcus thermophilus”. In Encyclopedia of Dairy Sciences (2nd) (2011): 143-148.
- Mullan WMA. “Starter Cultures: Importance of Selected Genera”. In Encyclopedia of Food Microbiology (2nd) (2011): 515-521.
- Radke-Mitchell LC and Sandine WE. “Influence of temperature on associative growth of Streptococcus thermophilus and Lactobacillus bulgaricus”. Journal of Dairy Science10 (1986): 2558-2568.
- Lee SH., et al. “Immunological pathogenesis of inflammatory bowel disease”. Intestinal Research1 (2018): 26-42.
- Longo S., et al. “New Insights into Inflammatory Bowel Diseases from Proteomic and Lipidomic Studies”. Proteomes3 (2020): 18.
- Baumgart DC and Carding SR. “Inflammatory bowel disease: cause and immunobiology”. The Lancet 369 (2007): 1627-1640.
- Baumgart DC and Sandborn WJ. “Inflammatory bowel disease: clinical aspects and established and evolving therapies”. The Lancet 369 (2007): 1641-1657.
- Slebioda TJ and Kmiec Z. “Tumour Necrosis Factor Superfamily Members in the Pathogenesis of Inflammatory Bowel Disease”. Mediators of Inflammation (2014): 325129.
- Kedia S and Ahuja V. “Epidemiology of Inflammatory Bowel Disease in India: The Great Shift East”. Inflammatory Bowel Disease2 (2017): 102-115.
- Mak WY., et al. “The epidemiology of inflammatory bowel disease: East meets west”. Journal of Gastroenterology and Hepatology3 (2020): 380-389.
- Hammer T and Langholz E. “The epidemiology of inflammatory bowel disease: balance between East and West? A narrative review”. Digestive Medicine Research 3 (2020): 48.
- Okumura R and Takeda K. “Roles of intestinal epithelial cells in the maintenance of gut homeostasis”. Experimental and Molecular Medicine 5 (2017): e338.
- Eichele DD and Kharbanda KK. “Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis”. World Journal of Gastroenterology 33 (2017): 6016-6029.
- Silva I., et al. “Preclinical Study in Vivo for New Pharmacological Approaches in Inflammatory Bowel Disease: A Systematic Review of Chronic Model of TNBS-Induced Colitis”. Journal of Clinical Medicine10 (2019): 1574.
- Mishra R., et al. “Inflammatory Bowel Disease: Therapeutic limitations and prospective of the stem cell therapy”. World Journal of Stem Cells10 (2020): 1050-1066.
- Mosmann T. “Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays”. Journal of Immunology Methods 1-2 (1983): 55-63.
- Muñoz M., et al. “Measurement of reactive oxygen intermediate production in haemocytes of the penaeid shrimp, Penaeus vannamei”. Aquaculture 1-3 (2000): 89-107.
- Choi HS., et al. “A quantitative nitroblue tetrazolium assay for determining intracellular superoxide anion production in phagocytic cells”. Journal of Immunoassay and Immunochemistry 1 (2006): 31-44.
- Das R., et al. “Therapeutic Effect of Combinatorial Probiotics to Protect Intestinal Barrier Function”. EC Microbiology2 (2017): 84-95.
- Haney EF., et al. “Critical Assessment of Methods to Quantify Biofilm Growth and Evaluate Antibiofilm Activity of Host Defence Peptides”. Biomolecules2 (2018): 29.
- Park SY., et al. “Lower expression of endogenous intestinal alkaline phosphatase may predict worse prognosis in patients with Crohn's disease”. BMC Gastroenterology1 (2018): 188.
- Kanta P., et al. “An innovative and cost-effective way to estimate alkaline phosphatase activity in in vitro cellular model systems”. International Journal of Biochemistry and Molecular Biology 1 (2021): 1-7.
- Williams EA., et al. “Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study”. Aliment Pharmacology Therapy1 (2009): 97-103.
- Saez-Lara MJ., et al. “The Role of Probiotic Lactic Acid Bacteria and Bifidobacteria in the Prevention and Treatment of Inflammatory Bowel Disease and Other Related Diseases: A Systematic Review of Randomized Human Clinical Trials”. Biomed Research International 2015 (2015): 505878.
- Elsherif Y., et al. “Determinants of Weight Loss prior to Diagnosis in Inflammatory Bowel Disease: A Retrospective Observational Study”. Gastroenterology Research Practice 2014 (2014): 762191.
- Okba AM., et al. “Neutrophil/lymphocyte ratio and lymphocyte/monocyte ratio in ulcerative colitis as non-invasive biomarkers of disease activity and severity”. Autoimmunity Highlights 1 (2019): 4.
- Zhang J and Shi G. “Lymphocyte infiltration and key differentially expressed genes in the ulcerative colitis”. Medicine (Baltimore)35 (2020): e21997.
- Hamada Y., et al. “Increased cytoplasmic accumulation of goblet cell glycoproteins in ulcerative colitis”. Inflammatory Bowel Disease 2.2 (1996): 97-104.
- Soufli I., et al. “Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases”. World Journal of Gastrointestinal Pharmacology and Therapeutics 3 (2016): 353-360.
- Coburn LA., et al. “L-arginine Availability and Metabolism is Altered in Ulcerative Colitis”. Inflammatory Bowel Disease8 (2016): 1847-1858.
- Shah YM. “The role of hypoxia in intestinal inflammation”. Molecular and Cellular Pediatrics1 (2016): 1-5.
- Chen Y., et al. “A Role of Exopolysaccharide Produced by Streptococcus thermophilus in the Intestinal Inflammation and Mucosal Barrier in Caco-2 Monolayer and Dextran Sulphate Sodium-Induced Experimental Murine Colitis”. Molecules3 (2019): 513.
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