Lactococcus lactis D4 Has Potential Effect to Alleviate Inflammation and Reverse Dysbiosis in Colitis Rat Model
Abstract
BACKGROUND: Inflammatory bowel disease (IBD) is a prevalent chronic inflammatory disorder of the gastrointestinal tract that may lead to colorectal cancer if untreated. Several medications for IBD have adverse side effects. Thus, there are high interest for searching alternative treatment to treat IBD. Lactococcus lactis D4 isolated from dadih, a traditional fermented buffalo milk product, was investigated for the effect on gut inflammation and microbial composition in the colitis rat model.
METHODS: Eighteen male Sprague-Dawley rats were divided into three groups; control rats, colitis-induced rats, and colitis-induced rats treated with L. lactis D4 isolate. The control group received water, while the colitis-induced rats were given azoxymethane (AOM) and dextran sodium sulphate (DSS). Rats’ feces were collected for the analysis of gut microbiota diversity by next-generation sequencing and for the measurement of transforming growth factor (TGF)-β, nuclear factor kappa-B (NF-κB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α colonic expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
RESULTS: L. lactis D4 administration was able to reduce inflammation in colitis by decreasing IL-6 expression (0.87 vs. 0.73), while expression of TGF-β, NF-κB, and TNF-α were increased compared to the model group, suggesting a complex immunomodulatory effect. Gut microbiota sequencing revealed a similarity between the control and treatment groups, suggesting L. lactis D4 has great potential to ameliorate gut microbiota dysbiosis in colitis rats.
CONCLUSION: L. lactis D4 has a beneficial effect in decreasing pro-inflammatory cytokines and is able to reserve dysbiosis in colitis rat model. Thus, L. lactis D4 might be used as a therapeutic agent for IBD.
KEYWORDS: colitis, gut microbiota, inflammation, inflammatory bowel disease, Lactococcus lactis D4, probiotic, proinflammatory cytokines
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Alatab S, Sepanlou SG, Ikuta K, Vahedi H, Bisignano C, Safiri S, et al. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020; 5(1): 17–30, CrossRef.
Center of Disease Control and Prevention [Internet]. Prevalence of IBD [updated 2022 Apr 14; cited 2023 Nov 10]. Available from: https://www.cdc.gov/.
Simadibrata M, Adiwinata R. Current issues of gastroenterology in Indonesia. Acta Med Indones. 2017; 49(3): 270–8, PMID.
Godat S, Fournier N, Safroneeva E, Juillerat P, Nydegger A, Straumann A, et al. Frequency and type of drug-related side effects necessitating treatment discontinuation in the Swiss Inflammatory Bowel Disease Cohort. Eur J Gastroenterol Hepatol. 2018; 30(6): 612–20, CrossRef.
Giraud EL, Thomas PWA, van Lint JA, van Puijenbroek EP, Römkens TEH, West RL, et al. Adverse drug reactions from real-world data in inflammatory bowel disease patients in the IBDREAM registry. Drug Saf. 2021; 44(5): 581–8, CrossRef.
Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, et al. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis. 2011; 17(1): 179–84, CrossRef.
Berding K, Vlckova K, Marx W, Schellekens H, Stanton C, Clarke G, et al. Diet and the microbiota–gut–brain axis: Sowing the seeds of good mental health. Adv Nutr. 2021; 12(4): 1239–85, CrossRef.
Drago L. Probiotics and colon cancer. Microorganisms. 2019; 7(3): 66, CrossRef.
Valentina I, Achadiyani, Adi SS, Lesmana R, Farenia R. Effect of Lactobacillus reuteri administration on wrinkle formation and type I procollagen levels in UVB-exposed male Balb/c mice (Mus musculus). Mol Cell Biomed Sci. 2020; 4(3): 113–20, CrossRef.
Aindelis G, Chlichlia K. Modulation of anti-tumour immune responses by probiotic bacteria. Vaccines. 2020; 8(2): 329, CrossRef.
Mills S, Ross RP, Coffey A. Lactic acid bacteria : Lactococcus lactis. In: Fuquay JW, Fox PF, McSweeney PLH, editors. Encyclopedia of Dairy Science. 2nd Ed. San Diego: Academic Press; 2011. p.132–7, article.
Sukma A, Toh H, Tien NTT, Fitria N, Mimura I, Kaneko R, et al. Microbiota community structure in traditional fermented milk dadiah in Indonesia: Insights from high-throughput 16S rRNA gene sequencing. Milchwissenschaft. 2018; 71: 1–3, article.
World Health Organization [Internet]. General guidelines for methodologies on research and evaluation of traditional medicine [updated 2000 Nov 12; cited 2023 Nov 29]. Available from: https://www.who.int/.
Sukma A. Analysis of Microbiota in, and Isolation of Nisin-Producing Lactococcus lactis subsp. lactis Strains from, Indonesian Traditional Fermented Milk, Dadiah [Dissertation]. Okayama: Okayama University; 2017, article.
Stojanov S, Berlec A, Štrukelj B. The influence of probiotics on the Firmicutes/Bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. Microorganisms. 2020; 8(11): 1715, CrossRef.
Meiliana A, Wijaya A. Gut microbiota, obesity and metabolic dysfunction. Indones Biomed J. 2011; 3(3): 150–67, CrossRef.
Vaiserman A, Romanenko M, Piven L, Moseiko V, Lushchak O, Kryzhanovska N, et al. Differences in the gut Firmicutes to Bacteroidetes ratio across age groups in healthy Ukrainian population. BMC Microbiol. 2020; 20(1): 221, CrossRef.
Rizzatti G, Lopetuso LR, Gibiino G, Binda C, Gasbarrini A. Proteobacteria: A common factor in human diseases. Biomed Res Int. 2017: 2017: 9351507, CrossRef.
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 Food Sci Technol. 2023; 138: 178–98, CrossRef.
Dhillon P, Singh K. Therapeutic applications of probiotics in ulcerative colitis: An updated review. PharmaNutrition. 2020; 13: 100194, CrossRef.
Binda C, Lopetuso LR, Rizzatti G, Gibiino G, Cennamo V, Gasbarrini A. Actinobacteria: A relevant minority for the maintenance of gut homeostasis. Digestive and Liver Disease. 2018; 50(5): 421–8, CrossRef.
Kleerebezem M, Bachmann H, van Pelt-KleinJan E, Douwenga S, Smid EJ, Teusink B, et al. Lifestyle, metabolism and environmental adaptation in Lactococcus lactis. FEMS Microbiol Rev. 2020; 44(6): 804–20, CrossRef.
Arukha AP, Freguia CF, Mishra M, Jha JK, Kariyawasam S, Fanger NA, et al. Lactococcus lactis delivery of surface layer protein A protects mice from colitis by re-setting host immune repertoire. Biomedicines. 2021; 9(9): 1098, CrossRef.
DOI: https://doi.org/10.18585/inabj.v16i2.2970
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