DOI QR코드

DOI QR Code

The Combination of Bacillus natto JLCC513 and Ginseng Soluble Dietary Fiber Attenuates Ulcerative Colitis by Modulating the LPS/TLR4/NF-κB Pathway and Gut Microbiota

  • Mingyue Ma (Agronomy of Food Science and Technology, Yanbian University) ;
  • Yueqiao Li (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Yuguang He (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Da Li (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Honghong Niu (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Mubai Sun (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Xinyu Miao (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Ying Su (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Hua Zhang (Agronomy of Food Science and Technology, Yanbian University) ;
  • Mei Hua (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China)) ;
  • Jinghui Wang (Institute of Agro-product Process, Jilin Academy of Agricultural Science (Northeast Agricultural Research Center of China))
  • Received : 2024.02.19
  • Accepted : 2024.04.25
  • Published : 2024.06.28

Abstract

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is currently difficult to treat effectively. Both Bacillus natto (BN) and ginseng-soluble dietary fiber (GSDF) are anti-inflammatory and helps sustain the intestinal barrier. In this study, the protective effects and mechanism of the combination of B. natto JLCC513 and ginseng-soluble dietary fiber (BG) in DSS-induced UC mice were investigated. Intervention with BG worked better than taking BN or GSDF separately, as evidenced by improved disease activity index, colon length, and colon injury and significantly reduced the levels of oxidative and inflammatory factors (LPS, ILs, and TNF-α) in UC mice. Further mechanistic study revealed that BG protected the intestinal barrier integrity by maintaining the tight junction proteins (Occludin and Claudin1) and inhibited the LPS/TLR4/NF-κB pathway in UC mice. In addition, BG increased the abundance of beneficial bacteria such as Bacteroides and Turicibacter and reduced the abundance of harmful bacteria such as Allobaculum in the gut microbiota of UC mice. BG also significantly upregulated genes related to linoleic acid metabolism in the gut microbiota. These BG-induced changes in the gut microbiota of mice with UC were significantly correlated with changes in pathological indices. In conclusion, this study demonstrated that BG exerts protective effect against UC by regulating the LPS/TLR4/NF-κB pathway and the structure and metabolic function of gut microbiota. Thus, BG can be potentially used in intestinal health foods to treat UC.

Keywords

Acknowledgement

This work was supported by Jilin Province Agricultural Science and Technology Innovation Project (CXGC2022RCG001, CXGC2022RCY002), National Natural Science Foundation of China (32302106), and Changchun City Science and Technology Development Plan (21ZGN36). We would like to thank Editage (www.editage.cn) for English language editing.

References

  1. Wan Y, Yang L, Li H, Ren H, Zhu K, Dong Z, et al. 2022. Zingiber officinale and Panax ginseng ameliorate ulcerative colitis in mice via modulating gut microbiota and its metabolites. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1203: 123313.
  2. Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, et al. 2021. The international scientific association of probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat. Rev. Gastroenterol. Hepatol. 18: 649-667. https://doi.org/10.1038/s41575-021-00440-6
  3. Kim Y, Hwang SW, Kim S, Lee YS, Kim TY, Lee SH, et al. 2020. Dietary cellulose prevents gut inflammation by modulating lipid metabolism and gut microbiota. Gut Microbes 11: 944-961. https://doi.org/10.1080/19490976.2020.1730149
  4. Deng Q, Zhang L, Liu X, Kang L, Yi J, Ren J, Qu X. 2023. COF-based artificial probiotic for modulation of gut microbiota and immune microenvironment in inflammatory bowel disease. Chem. Sci. 14: 1598-1605. https://doi.org/10.1039/D2SC04984H
  5. Deng B, Wu J, Li X, Men X, Xu Z. 2017. Probiotics and probiotic metabolic product improved intestinal function and ameliorated LPS-induced injury in rats. Curr. Microbiol. 74: 1306-1315. https://doi.org/10.1007/s00284-017-1318-7
  6. Chung KS, Shin JS, Lee JH, Park SE, Han HS, Rhee YK, et al. 2021. Protective effect of exopolysaccharide fraction from Bacillus subtilis against dextran sulfate sodium-induced colitis through maintenance of intestinal barrier and suppression of inflammatory responses. Int. J. Biol. Macromol. 178: 363-372. https://doi.org/10.1016/j.ijbiomac.2021.02.186
  7. Sun R, Niu HH, Sun MB, Miao XY, Jin X, Xu XF, et al. 2022. Effects of Bacillus subtilis natto JLCC513 on gut microbiota and intestinal barrier function in obese rats. J. Appl. Microbiol. 133: 3634-3644. https://doi.org/10.1111/jam.15797
  8. Hua M, Sun Y, Shao Z, Lu J, Lu Y, Liu Z. 2020. Functional soluble dietary fiber from ginseng residue: polysaccharide characterization, structure, antioxidant, and enzyme inhibitory activity. J. Food Biochem. 44: e13524.
  9. Li H, Fan C, Lu H, Feng C, He P, Yang X, et al. 2020. Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions. Acta Pharm. Sin. B 10: 447-461. https://doi.org/10.1016/j.apsb.2019.08.006
  10. Dieleman L, Palmen M, Akol H. 1998. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin. Exp. Immunol. 114: 385-391. https://doi.org/10.1046/j.1365-2249.1998.00728.x
  11. Huang S, Fu Y, Xu B, Liu C, Wang Q, Luo S, et al. 2020. Wogonoside alleviates colitis by improving intestinal epithelial barrier function via the MLCK/pMLC2 pathway. Phytomedicine 68: 153179.
  12. Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, O'NeilD A, et al. 2005. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54: 242-249. https://doi.org/10.1136/gut.2004.044834
  13. Kamarli Altun H, Akal Yildiz E, Akin M. 2019. Effects of synbiotic therapy in mild-to-moderately active ulcerative colitis: a randomized placebo-controlled study. Turk. J. Gastroenterol. 30: 313-320. https://doi.org/10.5152/tjg.2019.18356
  14. Jiang X, Ding H, Liu Q, Wei Y, Zhang Y, Wang Y, et al. 2020. Effects of peanut meal extracts fermented by Bacillus natto on the growth performance, learning and memory skills and gut microbiota modulation in mice. Br. J. Nutr. 123: 383-393. https://doi.org/10.1017/S0007114519002988
  15. Wu C, Ouyang M, Guo Q, Jia J, Liu R, Jiang Y, et al. 2019. Changes in the intestinal microecology induced by Bacillus subtilis inhibit the occurrence of ulcerative colitis and associated cancers: a study on the mechanisms. Am. J. Cancer Res. 9: 872-886.
  16. Kimelman H, Shemesh M. 2019. Probiotic bifunctionality of Bacillus subtilis-rescuing lactic acid bacteria from desiccation and antagonizing pathogenic Staphylococcus aureus. Microorganisms 7: 407.
  17. Rhayat L, Maresca M, Nicoletti C, Perrier J, Brinch KS, Christian S, et al. 2019. Effect of Bacillus subtilis strains on intestinal barrier function and inflammatory response. Front. Immunol. 10: 564.
  18. Wang P, Gao X, Li Y, Wang S, Wei Y. 2020. Bacillus natto regulates gut microbiota and adipose tissue accumulation in a high-fat diet mouse model of obesity. J. Funct. Foods 68: 103923.
  19. Riaz M, Rahman NU, Zia-Ul-Haq M, Jaffar HZE, Manea R. 2018. Ginseng: a dietary supplement as immune-modulator in various diseases. Trends Food Sci. Technology 83: 12-30. https://doi.org/10.1016/j.tifs.2018.11.008
  20. Yu Y, Yang W, Yu T, Zhao X, Zhou Z, Yu Y, et al. 2022. Glucose promotes regulatory T cell differentiation to maintain intestinal homeostasis. iScience 25: 105004.
  21. Dong L, Xie J, Wang Y, Jiang H, Chen K, Li D, et al. 2022. Mannose ameliorates experimental colitis by protecting intestinal barrier integrity. Nat. Commun. 13: 4804.
  22. Shinde T, Perera AP, Vemuri R. 2019. Synbiotic supplementation containing whole plant sugar cane fibre and probiotic spores potentiates protective synergistic effects in mouse model of IBD. Nutrients 11: 15028.
  23. Sawoo R, Dey R, Ghosh R, Bishayi B. 2023. Exogenous IL-10 posttreatment along with TLR4 and TNFR1 blockade improves tissue antioxidant status by modulating sepsis-induced macrophage polarization. J. Appl. Toxicol. 43: 1549-1572.
  24. Zhang D, Jing B, Chen ZN, Li X, Shi HM, Zheng YC, et al. 2023. Ferulic acid alleviates sciatica by inhibiting neuroinflammation and promoting nerve repair via the TLR4/NF-κB pathway. CNS Neurosci. Ther. 29: 1000-1011. https://doi.org/10.1111/cns.14060
  25. Verma IM, Scevenson JK, Schwarz EM. 1995. Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev. 9: 2723-2735. https://doi.org/10.1101/gad.9.22.2723
  26. Xie L, Chi X, Wang H, Dai A, Dong J, Liu S, et al. 2023. Mechanism of action of buckwheat quercetin in regulating lipid metabolism and intestinal flora via Toll-like receptor 4 or nuclear factor κB pathway in rats on a high-fat diet. Nutrition 115: 112148.
  27. Zhang T, Ji X, Lu G, Zhang F. 2021. The potential of Akkermansia muciniphila in inflammatory bowel disease. Appl. Microbiol. Biotechnol. 105: 5785-5794. https://doi.org/10.1007/s00253-021-11453-1
  28. He NN, Yang Y, Wang HY, Liu N, Yang ZZ, Li SY. 2021. Unsaturated alginate oligosaccharides (UAOS) protects against dextran sulfate sodium-induced colitis associated with regulation of gut microbiota. J. Functional Foods 83: 104536.
  29. Rice TA, Bielecka AA, Nguyen MT, Rosen CE, Song D, Sonnert ND, et al. 2022. Interspecies commensal interactions have nonlinear impacts on host immunity. Cell Host Microbe 30: 988-1002.e1006. https://doi.org/10.1016/j.chom.2022.05.004
  30. Lee JY, Hall JA, Kroehling L, Wu L, Najar T, Nguyen HH, et al. 2020. Serum amyloid a proteins induce pathogenic Th17 cells and promote inflammatory disease. Cell 180: 79-91.e16. https://doi.org/10.1016/j.cell.2019.11.026
  31. van Muijlwijk GH, van Mierlo G, Jansen P, Vermeulen M, Bleumink-Pluym NMC, Palm NW, et al. 2021. Identification of Allobaculum mucolyticum as a novel human intestinal mucin degrader. Gut Microbes 13: 1966278.
  32. Thomann AK, Wustenberg T, Wirbel J, Knoedler LL, Thomann PA, Zeller G, et al. 2022. Depression and fatigue in active IBD from a microbiome perspective-a Bayesian approach to faecal metagenomics. BMC Med. 20: 366.
  33. Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A. 2020. The genus alistipes: gut bacteria with emerging implications to inflammation, cancer, and mental health. Front. Immunol. 11: 906.
  34. Yao M, Guo X, Shao X, Wei Y, Zhang X, Wang H, et al. 2023. Soluble dietary fiber from Prunus persica dregs alleviates gut microbiota dysfunction through lead excretion. Food Chem. Toxicol. 175: 113725.
  35. Stoeva MK, Garcia-So J, Justice N, Myers J, Tyagi S, Nemchek M, et al. 2021. Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut Microbes 13: 1-28.
  36. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. 2008. Review article: the role of butyrate on colonic function. Aliment. Pharmacol. Ther. 27: 104-119. https://doi.org/10.1111/j.1365-2036.2007.03562.x
  37. Rose S, Bennuri SC, Davis JE, Wynne R, Slattery JC, Tippett M, et al. 2018. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism. Transl. Psychiatry 8: 42.
  38. Laserna-Mendieta EJ, Clooney AG, Carretero-Gomez JF, Moran C, Sheehan D, Nolan JA, et al. 2018. Determinants of reduced genetic capacity for butyrate synthesis by the gut microbiome in Crohn's disease and ulcerative colitis. J. Crohns Colitis 12: 204-216. https://doi.org/10.1093/ecco-jcc/jjx137
  39. Liu H, Wang J, He T, Becker S, Zhang G, Li D, et al. 2018. Butyrate: a double-edged sword for health? Adv. Nutr. 9: 21-29. https://doi.org/10.1093/advances/nmx009
  40. Luo S, Wen R, Wang Q, Zhao Z, Nong F, Fu Y, et al. 2019. Rhubarb Peony Decoction ameliorates ulcerative colitis in mice by regulating gut microbiota to restoring Th17/Treg balance. J. Ethnopharmacol. 231: 39-49. https://doi.org/10.1016/j.jep.2018.08.033
  41. Lei S, Zhang Z, Xie G, Zhao C, Miao Y, Chen D, et al. 2022. Theabrownin modulates the gut microbiome and serum metabolome in aging mice induced by D-galactose. J. Funct. Foods 89: 104941.
  42. Yang JY, Lee YS, Kim Y, Lee SH, Ryu S, Fukuda S, et al. 2017. Gut commensal Bacteroides acidifaciens prevents obesity and improves insulin sensitivity in mice. Mucosal Immunol. 10: 104-116. https://doi.org/10.1038/mi.2016.42
  43. Nakajima A, Sasaki T, Itoh K, Kitahara T, Takema Y, Hiramatsu K, et al. 2020. A soluble fiber diet increases Bacteroides fragilis group abundance and immunoglobulin a production in the gut. Appl. Environ. Microbiol. 86: e00405-20. https://doi.org/10.1128/AEM.00405-20
  44. Wu L, Yan Q, Chen F, Cao C, Wang S. 2021. Bupleuri radix extract ameliorates impaired lipid metabolism in high-fat diet-induced obese mice via gut microbia-mediated regulation of FGF21 signaling pathway. Biomed. Pharmacother. 135: 111187.
  45. Chetwynd AJ, Ogilvie LA, Nzakizwanayo J, Pazdirek F, Hoch J, Dedi C, et al. 2019. The potential of nanoflow liquid chromatographynano electrospray ionisation-mass spectrometry for global profiling the faecal metabolome. J. Chromatogr. A 1600: 127-136. https://doi.org/10.1016/j.chroma.2019.04.028
  46. Milne GL, Yin H, Hardy KD, Davies SS, Roberts LJ. 2011. Isoprostane generation and function. Chem. Rev. 111: 5973-5996. https://doi.org/10.1021/cr200160h
  47. Ramsden CE, Ringel A, Feldstein AE, Taha AY, MacIntosh BA, Hibbeln JR, et al. 2012. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids 87: 135-141. https://doi.org/10.1016/j.plefa.2012.08.004
  48. Miyamoto J, Mizukure T, Park SB, Kishino S, Kimura I, Hirano K, et al. 2015. A gut microbial metabolite of linoleic acid, 10-hydroxycis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway. J. Biol. Chem. 290: 2902-2918. https://doi.org/10.1074/jbc.M114.610733