Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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The Human Milk Oligosaccharide 2'-Fucosyllactose Shows an Immune-Enhancing Effect in a Cyclophosphamide-Induced Mouse Model

  • Seon Ha Jo (Department of Nano Bio Engineering, Seoul National University of Science and Technology) ;
  • Kyeong Jin Kim (Department of Nano Bio Engineering, Seoul National University of Science and Technology) ;
  • Soo-yeon Park (Department of Food Science and Technology, Seoul National University of Science and Technology) ;
  • Hyun-Dong Paik (Department of Food Science and Biotechnology of Animal Resources, Konkuk University) ;
  • Ji Yeon Kim (Department of Nano Bio Engineering, Seoul National University of Science and Technology)
  • Received : 2022.11.25
  • Accepted : 2022.12.06
  • Published : 2023.03.28
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Abstract

The 2'-fucosyllactose (2'-FL) is the richest components in a human milk oligosaccharide. Several studies have reported that 2'-FL has beneficial effects in infants. However, there are few studies on its immune-enhancing effects. This research aimed to examine the immune-enhancing effect of 2'-FL on immunosuppression by cyclophosphamide (CCP) in ICR mice. Mice were orally administered distilled water or 0.5 mg/kg B.W. 2'-FL for 14 days. An immunocompromised mouse model was induced using CCP 80 mg/kg B.W. at 12-14 days. Using the CCP had effects on reducing their body weight, organ weight, spleen index, natural killer (NK) cell activity, and cytokines concentration and expression. This study also used concanavalin A-mediated T-cell proliferation to verify the immune-enhancing effects in the sample. Body weight, spleen index, organ weight, and cytokine levels were measured to estimate the immune-enhancing effects. The body weight at 14 days tended to increase, and the spleen weight and index significantly increased in the 2'-FL group compared to the CCP group. The NK cell activity increased in the 2'-FL group compared to the CCP group, but there was no significant difference. The concentration of interleukin (IL)-2 tended to recover in the 2'-FL group compared to the CCP group. The 2'-FL group showed a significant increase of IL-10 and IFN-gamma concentration compared to the CCP group. In addition, there was a trend of increased IL-10 mRNA expression compared to the CCP group. These results revealed that 2'-FL improved CCP-induced immunosuppression, suggesting that 2'-FL may have the potential to enhance the immune system.

Keywords

Acknowledgement

This work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, and Forestry (IPET) through the Innovational Food Technology Development Program (#119009-3), funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA).

References

  1. Prentice AM, Prentice A. 1995. Evolutionary and enviromental influences on human lactation. Proc. Nutr. Soc. 54: 391-400. https://doi.org/10.1079/PNS19950008
  2. Ladomenou F, Moschandreas J, Kafatos A, Tselentis Y, Galanakis E. 2010. Protective effect of exclusive breastfeeding against infections during infancy: a prospective study. Arch. Dis. Child. 95: 1004-1008. https://doi.org/10.1136/adc.2009.169912
  3. Italianer MF, Naninck EFG, Roelants JA, van der Horst GTJ, Reiss IKM, Goudoever JBV, et al. 2020. Circadian variation in human milk composition, a systematic review. Nutrients 12: 2328.
  4. Casado B, Affolter M, Kussmann M. 2009. OMICS-rooted studies of milk proteins, oligosaccharides and lipids. J. Proteomics 73: 196-208. https://doi.org/10.1016/j.jprot.2009.09.018
  5. Buescher ES. 2001. Anti-inflammatory characteristics of human milk: how, where, why. Adv. Exp. Med. Biol. 501: 207-222. https://doi.org/10.1007/978-1-4615-1371-1_27
  6. Kong C, Faas MM, de Vos P, Akkerman R. 2020. Impact of dietary fibers in infant formulas on gut microbiota and the intestinal immune barrier. Food Funct. 11: 9445-9467. https://doi.org/10.1039/D0FO01700K
  7. Bode L. 2012. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology 22: 1147-1162. https://doi.org/10.1093/glycob/cws074
  8. Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL. 2014. Breast milk oligosaccharides: structure-function relationships in the neonate. Annu. Rev. Nutr. 34: 143-169. https://doi.org/10.1146/annurev-nutr-071813-105721
  9. Duska-McEwen G, Senft AP, Ruetschilling TL, Barrett EG, Buck RH. 2014. Human milk oligosaccharides enhance innate immunity to respiratory syncytial virus and influenza in vitro. Food Nutr. Sci. 14: 13.
  10. Reverri EJ, Devitt AA, Kajzer JA, Baggs GE, Borschel MW. 2018. Review of the clinical experiences of feeding infants formula containing the human milk oligosaccharide 2'-fucosyllactose. Nutrients 10: 1346.
  11. Goehring KC, Marriage BJ, Oliver JS, Wilder JA, Barrett EG, Buck RH. 2016. Similar to those who are breastfed, infants fed a formula containing 2'-fucosyllactose have lower inflammatory cytokines in a randomized controlled trial. J. Nutr. 146: 2559-2566. https://doi.org/10.3945/jn.116.236919
  12. Arnold H, Bourseaux F, Brock N. 1958. Chemotherapeutic action of a cyclic nitrogen mustard phosphamide ester (B 518-ASTA) in experimental tumours of the rat. Nature 181: 931-931. https://doi.org/10.1038/181931a0
  13. Shirani K, Hassani FV, Razavi-Azarkhiavi K, Heidari S, Zanjani BR, Karimi G. 2015. Phytotrapy of cyclophosphamide-induced immunosuppression. Environ. Toxicol. Pharmacol. 39: 1262-1275. https://doi.org/10.1016/j.etap.2015.04.012
  14. Pass GJ, Carrie D, Boylan M, Lorimore S, Wright E, Houston B, et al. 2005. Role of hepatic cytochrome p450s in the pharmacokinetics and toxicity of cyclophosphamide: studies with the hepatic cytochrome p450 reductase null mouse. Cancer Res. 65: 4211-4217. https://doi.org/10.1158/0008-5472.CAN-04-4103
  15. Al-Nasser IA. 1998. In vivo prevention of cyclophosphamide-induced Ca2+ dependent damage of rat heart and liver mitochondria by cyclosporin A. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 121: 209-214. https://doi.org/10.1016/S1095-6433(98)10135-6
  16. Kanneganti T-D, Lamkanfi M, Amer AO. 2012. Innate immune pathways in host defense. Mediators Inflammn. 2012: 708972.
  17. Lee H-N, Choi J-H, Park J-Y, Ahn J-H, Jang DE, Shim JG, et al. 2021. Combination of vegetable soup and glucan demonstrates synergistic effects on macrophage-mediated immune responses. Food Sci. Biotechnol. 30: 583-588. https://doi.org/10.1007/s10068-021-00888-x
  18. Germic N, Frangez Z, Yousefi S, Simon H-U. 2019. Regulation of the innate immune system by autophagy: neutrophils, eosinophils, mast cells, NK cells. Cell Death Differ. 26: 703-714. https://doi.org/10.1038/s41418-019-0295-8
  19. Lim JS, Kim CR, Shin KS, Lee SJ, Yoon TJ, Park HJ. 2021. Synergistic effect of Korean red ginseng extract and GABA mixture on the IgE production in mice via Th1/Th2 cell balance. Food Sci. Biotechnol. 30: 1571-1580. https://doi.org/10.1007/s10068-021-00985-x
  20. Donovan SM, Comstock SS. 2016. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Ann. Nutr. Metab. 69: 41-51. https://doi.org/10.1159/000452818
  21. Vos AP, M'Rabet L, Stahl B, Boehm G, Garssen J. 2007. Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates. Crit. Rev. Immunol. 27: 97-140. https://doi.org/10.1615/CritRevImmunol.v27.i2.10
  22. Chen LX, Qi YL, Qi Z, Gao K, Gong RZ, Shao ZJ, et al. 2019. A Comparative study on the effects of different parts of Panax ginseng on the immune activity of cyclophosphamide-induced immunosuppressed mice. Molecules 24: 1096.
  23. Xu X, Zhang X. 2015. Effects of cyclophosphamide on immune system and gut microbiota in mice. Microbiol. Res. 171: 97-106. https://doi.org/10.1016/j.micres.2014.11.002
  24. Lori A, Perrotta M, Lembo G, Carnevale D. 2017. The Spleen: A Hub connecting nervous and immune systems in cardiovascular and metabolic diseases. Int. J. Mol. Sci. 18: 1216.
  25. Raj S, Gothandam KM. 2015. Immunomodulatory activity of methanolic extract of Amorphophallus commutatus var. wayanadensis under normal and cyclophosphamide induced immunosuppressive conditions in mice models. Food Chem. Toxicol. 81: 151-159. https://doi.org/10.1016/j.fct.2015.04.026
  26. Sarangi I, Ghosh D, Bhutia SK, Mallick SK, Maiti TK. 2006. Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans. Int. Immunopharmacol. 6: 1287-1297. https://doi.org/10.1016/j.intimp.2006.04.002
  27. Moretta A, Bottino C, Mingari MC, Biassoni R, Moretta L. 2002. What is a natural killer cell? Nat. Immunol. 3: 6-8. https://doi.org/10.1038/ni0102-6
  28. Lemire P, Galbas T, Thibodeau J, Segura M. 2017. Natural killer cell functions during the innate immune response to pathogenic Streptococci. Front. Microbiol. 8: 1196.
  29. Adib-Conquy M, Scott-Algara D, Cavaillon JM, Souza-Fonseca-Guimaraes F. 2014. TLR-mediated activation of NK cells and their role in bacterial/viral immune responses in mammals. Immunol. Cell Biol. 92: 256-262. https://doi.org/10.1038/icb.2013.99
  30. Souza-Fonseca-Guimaraes F, Adib-Conquy M, Cavaillon JM. 2012. Natural killer (NK) cells in antibacterial innate immunity: angels or devils? Mol. Med. 18: 270-285. https://doi.org/10.2119/molmed.2011.00201
  31. Stordeur P, Zhou L, Byl B, Brohet F, Burny W, de Groote D, et al. 2003. Immune monitoring in whole blood using real-time PCR. J. Immunol. Methods 276: 69-77. https://doi.org/10.1016/S0022-1759(03)00074-7
  32. Castano AP, Mroz P, Wu MX, Hamblin MR. 2008. Photodynamic therapy plus low-dose cyclophosphamide generates antitumor immunity in a mouse model. Proc. Natl. Acad. Sci. USA 105: 5495-5500. https://doi.org/10.1073/pnas.0709256105
  33. Hamodrakas SJ, Kanellopoulos PN, Pavlou K, Tucker PA. 1997. The crystal structure of the complex of concanavalin A with 4'-methylumbelliferyl-alpha-D-glucopyranoside. J. Struct. Biol. 118: 23-30. https://doi.org/10.1006/jsbi.1996.3837
  34. Lovatt M, Yang T-H, Stauss HJ, Fisher AG, Merkenschlager M. 2000. Different doses of agonistic ligand drive the maturation of functional CD4 and CD8 T cells from immature precursors. Eur. J. Immunol. 30: 371-381. https://doi.org/10.1002/1521-4141(200002)30:2<371::AID-IMMU371>3.0.CO;2-T
  35. Arango Duque G, Descoteaux A. 2014. Macrophage cytokines: involvement in immunity and infectious diseases. Front. Immunol. 5: 491.
  36. Kak G, Raza M, Tiwari BK. 2018. Interferon-gamma (IFN-γ): exploring its implications in infectious diseases. Biomol. Concepts. 9: 64-79. https://doi.org/10.1515/bmc-2018-0007
  37. Azagra-Boronat I, Massot-Cladera M, Knipping K, Van't Land B, Stahl B, Garssen J, et al. 2018. Supplementation with 2'-FL and scGOS/lcFOS ameliorates rotavirus-induced diarrhea in suckling fats. Front. Cell Infect. Microbiol. 8: 372.
  38. Azagra-Boronat I, Massot-Cladera M, Mayneris-Perxachs J, Knipping K, Van't Land B, Tims S, et al. 2019. Immunomodulatory and prebiotic effects of 2'-fucosyllactose in suckling rats. Front. Immunol. 10: 1773.
  39. He Y, Liu S, Kling DE, Leone S, Lawlor NT, Huang Y, et al. 2016. The human milk oligosaccharide 2'-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation. Gut 65: 33-46. https://doi.org/10.1136/gutjnl-2014-307544
  40. Mosmann TR, Sad S. 1996. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today 17: 138-146. https://doi.org/10.1016/0167-5699(96)80606-2
  41. Rothermel AL, Gilbert KM, Weigle WO. 1991. Differential abilities of Th1 and Th2 to induce polyclonal B cell proliferation. Cell. Immunol. 135: 1-15. https://doi.org/10.1016/0008-8749(91)90249-B
  42. Donovan SM, Comstock SS. 2016. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Ann. Nutr. Metab. 69 Suppl 2: 42-51. https://doi.org/10.1159/000452818
  43. Yu ZT, Nanthakumar NN, Newburg DS. 2016. The human milk oligosaccharide 2'-fucosyllactose quenches campylobacter jejuni-induced inflammation in human epithelial cells HEp-2 and HT-29 and in mouse intestinal mucosa. J. Nutr. 146: 1980-1990. https://doi.org/10.3945/jn.116.230706
  44. Li A, Li Y, Zhang X, Zhang C, Li T, Zhang J, et al. 2021. The human milk oligosaccharide 2'-fucosyllactose attenuates β-lactoglobulin-induced food allergy through the miR-146a-mediated toll-like receptor 4/nuclear factor-κB signaling pathway. J. Dairy Sci. 104: 10473-10484. https://doi.org/10.3168/jds.2021-20257
  45. Monmai C, Nam JH, Lim JH, Rod-in W, Lee TH, Park WJ. 2021. Anti-inflammatory activities of the mixture of strawberry and rice powder as materials of fermented rice cake on RAW264.7 macrophage cells and mouse models. Food Sci. Biotechnol. 30: 1409-1416. https://doi.org/10.1007/s10068-021-00929-5