Clinical Significance of Excess Lactose in the Diet (Part 2)

O.Ye. Abaturov, A.O. Nikulina


The article on the basis of published data presents the ideas about the clinical significance of excess lactose in the diet. Lactose is a specific inhibitor of β-galactoside-binding protein — galectin-9 (Gal-9) which regulates the intracellular metabolism (cell growth, inflammation, immune response, apoptosis). Lactose, competitively binding to Gal-9, prevents activation of Gal-9/TIM-3-associated signaling pathways that promotes proliferation of the T-helper 1 and 17 cells, causing the induction of inflammation. Excess lactose reduces Treg-cells representation, which have immunosuppressive action, and increases insulin resistance. Lactose inhibits the interaction of Gal-9 with immunoglobulin E and hyaluronan-binding molecule CD44 and contributes to allergic manifestations. The limitations of using exogenous lactase preparations for patho­gnomonic treatment of inflammatory and allergic diseases in children with lactase deficiency are presented.


lactose; LCT polymorphisms; galectin-9; inflammation; allergy; exogenous lactase


Abaturov AE, Agafonova A E, Gerasimenko ON, Krivusha EL. [Introduction to the immunology of infectious process for teachers and general practitioners - family medicine]. Kiev: OOO «Dzhuliya Print»; 2012; 172 р. Russian.

Abaturov AA, Nikulina AA, Petrenko LL. [The role of lactase deficiency in children]. International Journal of Pediatrics, Obstetrics and Gynecology]. 2015; 2(7): 51-62. Russian.

Delyagin VM, Kagramanova KG, Shugurina EG. i dr. [Lactase gene polymorphism in children with atopic diseases]. Pediatrics. 2008; 87(4):16-24. Russian.

Barjon C, Niki T, Verillaud B et al. A novel monoclonal antibody for detection of galectin-9 in tissue sections: application to human tissues infected by oncogenic viruses. Infectious agents and cancer. 2012;7: 16. doi:10.1186/1750-9378-7-16. doi:10.1186/1750-9378-7-16.

Chen X, Song CH, Liu ZQ et al. Intestinal epithelial cells express galectin-9 in patients with food allergy that plays a critical role in sustaining allergic status in mouse intestine. Allergy.2011;66:1038–1046. doi: 10.1111/j.1398-9995.2011.02585.x.

Chou F.C., Shieh S.J., Sytwu H.K. Attenuation of Th1 response through galectin-9 and T-cell Ig mucin 3 interaction inhibits autoimmune diabetes in NOD mice. Eur. J. Immunol. 2009; 39(9): 2403-2511. doi: 10.1002/eji. 200839177. doi: 10.1002/eji. 200839177.

Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab. 2013; 17(6): 883–894. doi:10.1016/j.cmet. 2013. 05.004. doi:10.1016/j.cmet.2013. 05.004.

Enattah N, Sahi T, Savilahti E et al. Identification of a variant associated with adult type hypolactasia. Nat. Genetic. 2002; 30:233–237. doi:10.1038/ng826.

Geng H, Zhang GM, Li D, Zhang H, Yuan Y, Zhu HG, et al. Soluble form of T cell Ig mucin 3 is an inhibitory molecule in T cell-mediated immune response. J Immunol. 2006;176(3):1411–20. doi: 10.4049/jimmunol.176.3.1411.

Golden-Mason L, Palmer BE, Kassam N et al Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells. J Virol. 2009 Sep;83(18):9122-30. doi: 10.1128/JVI.00639-09.

Gorman JV, Colgan JD. Regulation of T- cell responses by the receptor molecule Tim-3. Immunol Res. 2014; 59(1-3):56-65. doi:10.1007/s12026-014-8524-1

Gumperz JE, Miyake S, Yamamura Т, Brenner MB. Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med. 2002 Mar 4;195(5):625-36. doi: 10.1084/jem.20011786.

Haining WN. Thinking inside the box: how T cell inhibitory receptors signal. Nat Med. 2012 Sep;18(9):1338-9. doi: 10.1038/nm.2921.

Han G, Chen G, Shen B, Li Y. Tim-3: an activation marker and activation limiter of innate immune cells. Front Immunol. 2013 Dec 10; 4:449. doi: 10.3389/fimmu. 2013.00449.

Hassan HY, van Erp A., Jaeger M., Tahir H. Genetic diversity of lactase persistence in East African populations. BMC Res Notes. 2016, Jan 4;9(1):8. doi: 10.1186/s13104-015-1833-1.

Jacobs J, Smits E, Lardon F, Pauwels P, Deschoolmeester V. Immune Checkpoint Modulation in Colorectal Cancer: What's New and What to Expect. J Immunol Res. 2015; 2015:158038. doi: 10.1155/2015/158038.

Keryer-Bibens C, Pioche-Durieu C, Villemant C et al. Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral latent membrane protein 1 and the immunomodulatory protein galectin 9. BMC Cancer. 2006; 6: 283. doi: 10.1186/1471-2407-6-283.

de Kivit S, Saeland E, Kraneveld AD et al. Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans. Allergy.2012;67:343–352. doi: 10.1111/j.1398-9995.2011.02771.x.

Koguchi K, Anderson DE, Yang L et al. Dysregulated T cell expression of TIM3 in multiple sclerosis. J Exp Med. 2006 Jun 12;203(6):1413-8. doi: 10.1084/jem.20060210.

Kurose Y, Wada J, Kanzaki M et al. Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease. BMC Nephrol. 2013 Jan 22;14:23. doi: 10.1186/1471-2369-14-23.

Lee J, Oh JM, Hwang JW et al. Expression of human TIM-3 and its correlation with disease activity in rheumatoid arthritis.Scand J Rheumatol. 2011;40(5):334–40. doi: 10.3109/03009742.2010.547871.

Leitner J, Rieger А, Pickl WJ et al. TIM-3 Does Not Act as a Receptor for Galectin-9. PLOS. 2013; 9(3):21 doi: 10.1371/journal.ppat.100325.

Lhuillier C, Barjon C, Niki T et al. Impact of exogenous galectin-9 on human T cells: contribution of the T cell receptor complex to antigen-independent activation but not to apoptosis induction. J. Biol. Chem. 2015; 290(27). doi:10.1074/jbc.M115.661272.

Li X, Chen G, Li Y et al. Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease. Clin Immunol. 2010 Feb;134(2):169 -77. doi: 10.1016/j.clim.2009.09.012.

Li Y, Feng J, Geng S et al. The N- and C-terminal carbohydrate recognition domains of galectin-9 contribute differently to its multiple functions in innate immunity and adaptive immunity. Mol Immunol. 2011; 48:670–677. doi: 10.1016/j. molimm. 2010.11.011.

Liberal R, Grant CR, Holder BS et al. The impaired immune regulation of autoimmune hepatitis is linked to a defective galectin-9/tim-3 pathway. Hepatology. 2012 Aug; 56(2):677-86. doi: 10.1002/hep.25682.

Ma CJ, Li GY, Cheng YQ et al. Cis-Association of Galectin-9 with Tim-3 Differentially Regulates IL-12/IL-23 Expressions in Monocytes via TLR Signaling. PLoS One. 2013 Aug 14;8(8):e72488. doi: 10.1371/journal.pone.0072488. eCollection 2013.

Madireddi S. Galectin-9 controls the therapeutic activity of 4-1BB-targeting antibodies/ S. Madireddi, S.Y. Eun, S.W. Lee, I. Nemčovičová// J Exp Med. 2014;211(7):1433-48. doi: 10.1084/jem.20132687.

Matsumoto R, Matsumoto H, Seki M, Hata M. Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes. J Biol Chem 1998;273:16976-16984. . doi: 10.1074/jbc.273.27.16976.

Mitra S, Ashisha S, Udupa V, Sheshadri S. Histological changes in intestine in semichronic diarrhea induced lactose enriched diet in rats: effect of Diarex Vet. Ind. J. of Еxp. Вiol. 2003; 41: 21–215. PMID:15267149.

Mrizak D, Martin N, Barjon C et al. Effect of nasopharyngeal carcinoma-derived exosomes on human regulatory T cells. J Natl Cancer Inst. 2015:107, 363. doi: 10.1093/jnci/dju363.

Niki T, Tsutsui S, Hirose S. et al. Galectin-9 is a high affinity IgE-binding lectin with anti-allergic effect by blocking IgE-antigen complex formation. J Biol Chem. 2009; 284: 32344–32352. doi: 10.1074/jbc.M109.035196.

Norling LV, Perretti M, Cooper D. Endogenous galectins and the control of the host inflammatory response. J. Endocrinol. 2009; 201(2):169-84. doi: 10.1677/JOE-08-0512

Oomizu S, Arikawa T, Niki T et al. Cell surface galectin-9 expressing th cells regulate Th17 and Foxp3(+) Treg development by galectin-9 secretion. PloS One 7, e48574. doi: 10.1371/journal.pone.0048574.

Paasela M, Kolho K-L, Vaarala O. et al. Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production. Br. J. Nutr. 2014; 112 (11):P1819–1825. doi:10.1017/S0007114514001998.

Rahman AN, Clayton K, Mujib S, Fong IW, Ostrowski MA. TIM-3 and Its Immunoregulatory Role in HIV Infection. J Clin Cell Immunol. 2012;7:007. doi:10.4172/2155-9899.S7-007.

Raithel M, Weidenhiller M, Hagel AF. The malabsorption of commonly occurring mono and disaccharides: levels of investigation and differential diagnoses. DtschArztebl. Int. 2013; 110(46):775-782. doi: 10.3238/ arztebl.2013.0775.

Sakaguchi S, Ohkura N. Foxo1 and Foxo3 help Foxp3. mmunity. 2010;33(6):835-7. doi: 10.1016/j.immuni.2010.12.004.

Sakuishi K, Jayaraman P, Behar SM, Anderson AC, Kuchroo VK. Emerging Tim-3 functions in antimicrobial and tumor immunity. Trends Immunol. 2011; 32(8):345-9. doi: 10.1016/ 2011. 05.003.

Sehrawat S, Reddy PBJ, Rajasagi N et al. Galectin-9/TIM-3 Interaction Regulates Virus-Specific Primary and Memory CD8+T Cell Response. PLoS Pathog. 2010; 6(5): e1000882. doi:10.1371/journal. ppat.1000882.

Shevach EM, Thornton AM. tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev. 2014 ;259(1):88-102. doi: 10.1111/imr.12160.

Su EW, Bi S, Kane LP. Galectin-9 regulates T helper cell function independently of Tim-3. Glycobiology. 2011; 21:1258–1265. doi: 10.1093/glycob/cwq214.

Sziksz E, Vannay A, Haczku A. Galectin-9: a suppressor of food allergy? Allergy. 2012; 67(3):293-5. doi: 10.1111/j.1398-9995. 2011. 02774.x.

Than NG, Romero R., Balogh A. et al. Galectins: Double-edged Swords in the Cross-roads of Pregnancy Complications and Female Reproductive Tract Inflammation and Neoplasia. J. Pathol. Transl. Med. 2015 May; 49(3):181-208. doi: 10.4132/jptm. 2015. 02.25. Epub 2015 May 1; http: //

Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8(7):523-32. doi: 10.1038/nri2343.

de Vrese M, Laue C, Offick B, Soeth E, Repenning F et al. A combination of acid lactase from Aspergillus oryzae and yogurt bacteria improves lactose digestion in lactose maldigesters synergistically: A randomized, controlled, double-blind cross-over trial. Clin Nutr. 2015 Jun;34(3):394-9. doi: 10.1016/j.clnu.2014.06.012.

Wiersma VR, de Bruyn M, Helfrich W et al. Therapeutic potential of Galectin-9 in human disease. Med Res Rev. 2013;33: 102–126. doi: 10.1002/med.20249.

Wu C. Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells. Immunity. 2014;41(2):270-82. doi: 10.1016/j.immuni. 2014.06.011.

Yoshida H, Imaizumi T, Kumagai M. et al. Interleukin-1beta stimulates galectin-9 expression in human astrocytes. Neuroreport. 2001;12:3755–3758. doi: 10.1371/journal. pone. 0009504

Zhao Q, Liu F, Hou Z, Yuan C, Zhu X. High level production of β-galactosidase exhibiting excellent milk-lactose degradation ability from Aspergillus oryzae by codon and fermentation optimization. Appl Biochem Biotechnol. 2014 Mar;172(6):2787-99. doi: 10.1007/s12010-013-0684-2.

Zhu C, Anderson AC, Schubart A et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005; 6: 1245-1252. doi:10.1038/ni1271.

Copyright (c) 2016 CHILD`S HEALTH

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.


© Publishing House Zaslavsky, 1997-2018


   Seo анализ сайта