Original Article

Mechanism of Probiotic VSL#3 Inhibiting NF-κB and TNF-α on Colitis through TLR4-NF-κB Signal Pathway


Background: We aimed to investigate the effect of probiotic VSL#3 on NF-κB and TNF-α in rats with colitis and the correlation with TLR4-NF-κB signal pathway.

Methods: Sixty Sprague Dawley (SD) rats were divided into the control, model and therapy groups (n=20) according to the random number table. Rats in the model and therapy groups were modeled for colitis, and rats in the therapy group were intragastrically administered with probiotic VSL#3. The expression of TLR4 and NF-κB protein, and the levels of NF-κB, TLR4, and TNF-α mRNA in the colon tissue were detected. The concentration of TNF-α in the serum after modeling but before intragastric administration (T0), 3d (T1) and 7d after intragastric administration (T2) was detected.

Results: The expression of TLR4 and NF-κB p65 protein, and the levels of TLR4, NF-κB, and TNF-α mRAN in the therapy group decreased (P < 0.001). At T0, T1, and T2, the concentration of TNF-α in the model and control groups increased (P < 0.001). TLR4 and NF-κB in the therapy group were positively correlated with TNF-α mRAN (P < 0.050).Conclusion: In conclusion, probiotic VSL#3 inhibits the expression of NF-κB and TNF-α in rats with colitis through TLR4-NF-κB signal pathway, so it is expected to be a first choice drug for the treatment of colitis.

Conclusion: In conclusion, probiotic VSL#3 inhibits the expression of NF-κB and TNF-α in rats with colitis through TLR4-NF-κB signal pathway, so it is expected to be a first choice drug for the treatment of colitis.


1. Abt MC, McKenney PT, Pamer EG (2016). Clostridium difficile colitis: pathogenesis and host defence. Nat Rev Microbiol, 14: 609-620.
2. Cleynen I, Boucher G, Jostins L, et al (2016). Inherited determinants of Crohn's dis-ease and ulcerative colitis phenotypes: a genetic association study. Lancet, 387: 156-167.
3. Shivashankar R, Tremaine WJ, Harmsen WS, Loftus EV, Jr (2017). Incidence and Prevalence of Crohn's Disease and Ul-cerative Colitis in Olmsted County, Min-nesota from 1970 through 2010. Clin Gas-troenterol Hepatol, 15: 857-863.
4. Fumery M, Kohut M, Gower-Rousseau C, et al (2017). Incidence, Clinical Presenta-tion, and Associated Factors of Micro-scopic Colitis in Northern France: A Population-Based Study. Dig Dis Sci, 62: 1571-1579.
5. Pardi DS (2017). Diagnosis and Manage-ment of Microscopic Colitis. Am J Gastro-enterol, 112: 78-85.
6. Studd C, Cameron G, Beswick L, et al (2016). Never underestimate inflammato-ry bowel disease: High prevalence rates and confirmation of high incidence rates in Australia. J Gastroenterol Hepatol, 31: 81-86.
7. Yao P, Cui M, Wang H, Gao H, Wang L, Yang T, Cheng Y (2016). Quantitative Analysis of Intestinal Flora of Uygur and Han Ethnic Chinese Patients with Ulcera-tive Colitis. Gastroenterol Res Pract, 2016: 9186232.
8. Pelka K, Shibata T, Miyake K, Latz E (2016). Nucleic acid-sensing TLRs and autoim-munity: novel insights from structural and cell biology. Immunol Rev, 269: 60-75.
9. Shimizu T (2016). Inflammation-inducing Factors of Mycoplasma pneumoniae. Front Mi-crobiol, 7: 414.
10. Tamaki H, Nakase H, Inoue S, et al (2016). Efficacy of probiotic treatment with Bifidobacterium longum 536 for induc-tion of remission in active ulcerative coli-tis: A randomized, double-blinded, place-bo-controlled multicenter trial. Dig Endosc, 28: 67-74.
11. Islam SU (2016). Clinical Uses of Probiotics. Medicine (Baltimore), 95: e2658.
12. Kumar M, Kissoon-Singh V, Coria AL, Moreau F, Chadee K (2017). Probiotic mixture VSL#3 reduces colonic inflam-mation and improves intestinal barrier function in Muc2 mucin-deficient mice. Am J Physiol Gastrointest Liver Physiol, 312: G34-g45.
13. Luo SY, Li R, Le ZY, Li QL, Chen ZW (2017). Anfibatide protects against rat cerebral ischemia/reperfusion injury via TLR4/JNK/caspase-3 pathway. Eur J Pharmacol, 807: 127-137.
14. Li J, Bao L, Zha D, Zhang L, Gao P, Zhang J, Wu X (2018). Oridonin protects against the inflammatory response in diabetic nephropathy by inhibiting the TLR4/p38-MAPK and TLR4/NF-κB signaling pathways. Int Immunopharmacol, 55: 9-19.
15. Yang Y, He J, Suo Y, et al (2016). Taurour-sodeoxycholate improves 2, 4, 6-trinitrobenzenesulfonic acid-induced ex-perimental acute ulcerative colitis in mice. Int Immunopharmacol, 36: 271-276.
16. Kane JS, Rotimi O, Ford AC (2017). Macro-scopic findings, incidence and character-istics of microscopic colitis in a large co-hort of patients from the United King-dom. Scand J Gastroenterol, 52: 988-994.
17. Zheng Z, Jiang H, Huang Y, Wang J, Qiu L, Hu Z, Ma X, Lu Y (2016). Screening of an anti-inflammatory peptide from Hy-drophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis. Sci Rep, 6: 25672.
18. Uppal V, Kreiger P, Kutsch E (2016). Eo-sinophilic Gastroenteritis and Colitis: a Comprehensive Review. Clin Rev Allergy Immunol, 50: 175-188.
19. Derikx LA, Dieleman LA, Hoentjen F (2016). Probiotics and prebiotics in ulcer-ative colitis. Best Pract Res Clin Gastroenterol, 30: 55-71.
20. Cui Y, Wei H, Lu F, Liu X, Liu D, Gu L, Ouyang C (2016). Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice. PLoS One, 11: e0148241.
21. Aoudia N, Rieu A, Briandet R, Deschamps J, Chluba J, Jego G, Garrido C, Guzzo J (2016). Biofilms of Lactobacillus planta-rum and Lactobacillus fermentum: Effect on stress responses, antagonistic effects on pathogen growth and immunomodu-latory properties. Food Microbiol, 53: 51-59.
22. Feng Y, Cui Y, Gao JL, et al (2016). Resveratrol attenuates neuronal autopha-gy and inflammatory injury by inhibiting the TLR4/NF-kappaB signaling pathway in experimental traumatic brain injury. Int J Mol Med, 37: 921-930.
23. Mukherjee S, Karmakar S, Babu SP (2016). TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. Braz J Infect Dis, 20: 193-204.
24. Liu T, Zhang L, Joo D, Sun SC (2017). NF-kappaB signaling in inflammation. Signal Transduct Target Ther, 2. pii: 17023.
25. Christian F, Smith EL, Carmody RJ (2016). The Regulation of NF-kappaB Subunits by Phosphorylation. Cells, 5(1). pii: E12.
26. He X, Wei Z, Wang J, Kou J, Liu W, Fu Y, Yang Z (2016). Alpinetin attenuates in-flammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis. Sci Rep, 6: 28370.
27. Wu H, Liu J, Li W, Liu G, Li Z (2016). LncRNA-HOTAIR promotes TNF-alpha production in cardiomyocytes of LPS-induced sepsis mice by activating NF-kappaB pathway. Biochem Biophys Res Commun, 471: 240-246.
28. Ahn S, Siddiqi MH, Aceituno VC, Simu SY, Zhang J, Perez ZE, Kim YJ, Yang DC (2016). Ginsenoside Rg5:Rk1 attenuates TNF-alpha/IFN-gamma-induced pro-duction of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-kappaB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages. In Vitro Cell Dev Biol Anim, 52: 287-295.
29. Zhou JT, Wang TT, Dou YX, et al (2018). Brusatol ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced ex-perimental colitis in rats: Involvement of NF-κB pathway and NLRP3 inflam-masome. Int Immunopharmacol, 64: 264-274.
30. Jang HM, Kang GD, Van Le TK, Lim SM, Jang DS, Kim DH (2017). 4-Methoxylonchocarpin attenuates inflam-mation by inhibiting lipopolysaccharide binding to Toll-like receptor of macro-phages and M1 macrophage polarization. Int Immunopharmacol, 45: 90-97.
IssueVol 48 No 7 (2019) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v48i7.2953
Probiotics VSL#3 NF-κB TLR4 TNF-α

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
WANG H, LI S, LI H, DU F, GUAN J, WU Y. Mechanism of Probiotic VSL#3 Inhibiting NF-κB and TNF-α on Colitis through TLR4-NF-κB Signal Pathway. Iran J Public Health. 48(7):1292-1300.