ÇOCUKLARDA HELİKOBAKTER PYLORİ ENFEKSİYONU İLE PLAZMA 25 HİDROKSİ VİTAMİN D3 DÜZEYİ ARASINDAKİ İLİŞKİ
Year 2023,
Volume: 24 Issue: 3, 343 - 349, 13.07.2023
Gülseren Evirgen Şahin
,
Erhun Kasırga
,
Semin Ayhan
Abstract
OBJECTIVE: The severity of the Helicobacter pylori (H.pylori) infection and the presence H.pylori related diseases are affected by host, bacterial and environmental factors. In this study it is aimed to show relationship between H.pylori infection and plasma Vitamin D3 (vitD3) has significant role in regulation inflamatory response in children with H.pylori infection.
MATERIAL AND METHODS: Two hundred one patients aged between 3-18 years, referred to pediatric gastroentrology department of Celal Bayar University Medical Faculty between March 2010 to March 2011 and performed upper gastrointestinal endoscopy because of gastrointestinal symptoms and iron deficiency anemia refractory to medical therapy were enrolled in this study. Histopathologic diagnosis of biopsy speciments of the patients were evaluated. There were 98 patients in H.pylori positive group and 103 patients in H.pylori negative group. Plasma level of vitD3 of H.pylori positive and H.pylori negative cases were compared. Relationship between gastric mucosal activity the degree of inflammation severity and vitD3 level were evaluated in the H.pylori positive group.
RESULTS: Vitamin D3 levels were low in 80 (81.6%) H.pylori positive patients and in 76 (73%) H.pylori negative patients. This difference was not statistically significant (p>0.05). The mean value of plasma level of vitD3 H.pylori positive and negative groups were 15.64±8.9 ng/mL and 16.36±11.35 ng/mL respectively. The difference between the groups was not statistically significant (p>0.05). When patients in H.pylori positive and negative groups were classified according to plasma vitD3 level in four different groups as severe deficiency, deficiency, insuficiency and sufficiency. Vitamin D3 severe deficiency in H.pylori positive group was statistically more frequent than H.pylori negative group (p<0.05). Severity of chronic inflamation and tissue H.pylori activity increased inversely with the mean vitD3 level in both groups (p<0.05).
CONCLUSIONS: Results of this study suggests that vitD3 deficiency is common in children in our region. Vitamin D3 deficiency is risk factor for H.pylori infection. The findings of this study shows vitD3 increasing antibacterial effect and reducing the severity of inflammation in H.pylori infection.
Supporting Institution
This project was funded by the Scientific Research department of Celal Bayar University , Manisa,
Project Number
Grant number. (332/140/1431)
References
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- 7. Martineau AR, JolliffeDA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019;23:(2)1–44.
- 8. Laplana M, Royo JL, Fibla J. Vitamin D Receptor polymorphisms and risk of enveloped virus infection: A meta-analysis. Gene. 2018;678:384-94.
- 9. Ismailova A, White JH. Vitamin D, infections and immunity. Rev Endocr Metab Disord. 2022;23(2):265-77.
- 10. Hafeez AB, Jiang X, Bergen PJ, Zhu Y. Antimicrobial Peptides: An Update on Classifications and Databases. Int J Mol Sci. 2021;22(21):11691.
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- 12. Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin
D3. FASEB J. 2005;19(9):1067-77.
- 13. O’Neil DA, Cole, SP, Martin-Porter E, et al. Regulation of human β-defensins by gastric epithelial cells in response to infection with Helicobacter pylori or stimulation with interleukin-1. Infect Immun. 2000;9:5412–15.
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- 15. Hu W, Zhang L, Li MX, et al. Vitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells.. Autophagy.2019;15:707–25.
- 16. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81(3): 353–73.
- 17. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122(2):398-17.
- 18. Ailloud F, Didelot X, Woltemate S, et al. Within-host evolution of Helicobacter pylori shaped by niche-specific adaptation, intragastric migrations and selective sweeps. Nat Commun. 2019;10:2273.
- 19. Seo JH, Bortolin K, Jones NL. Review: Helicobacter pylori infection in children. Helicobacter. 2020;25(1): e12742.
- 20. Blosse A, Lehours P, Wilson KT, Alain P, Gobert AP. Helicobacter: Inflammation, immunology, and vaccines. Helicobacter. 2018;23:e12517.
- 21. Săsăran MO, Meliț LE, Dobru ED. MicroRNA Modulation of Host Immune Response and Inflammation Triggered by Helicobacter pylori. Int J Mol Sci. 2021;22(3):1406.
- 22. Doğan N, Çolak AA, Güden N, Üstüner F. Vitamin D deficiency in children in Aegean Region in Turkey. Cumhuriyet Medical Journal. 2015;37:17-22.
- 23. Özdemir AA, Gündemir YE, Küçük M et al. Vitamin D Deficiency in Pregnant Women and Their Infants. J Clin Res Pediatr Endocrinol. 2018;10(1):44–50.
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- 25. Andersen R, Molgaard C, Skovgaard LT, et al. Teenage girls and elderly women living in northern europe have low winter vitamin D status. Eur J Clin Nutr. 2005;59:533-41.
- 26. Mutua AM, Nampijja M, Elliott AM, et al. Vitamin D status is not associated with cognitive or motor function in preschool Ugandan children. Nutrients. 2020;12:1662.
- 27. Ní Chaoimh C, McCarthy EK, Hourihane JO, et al. Low vitamin D deficiency in Irish toddlers despite northerly latitude and a high prevalence of inadequate intakes. Eur J Nutr. 2018;57:783–94.
- 28. Kawaura A, Takeda E, Tanida N, et al. Inhibitory effect of long term 1alpha-hydroxyvitamin D3 administration on Helicobacter pylori infection. J Clin Biochem Nutr. 2006;38:103–06.
- 29. Antico A, Tozzoli R, Giavarina D, Tonutti E, Bizzaro N. Hypovitaminosis D as predisposing factor for atrop-hic type A gastritis: a case-control study and review of the literature on the interaction of Vitamin D with
the immune system. Clin Rev Allergy Immunol. 2012;42:355–64.
- 30. Gao T, Zhao M, Zhang C, et al. Association of Helicobacter pylori infection with vitamine D deficiency in infants and toddlers. Am J Trop Med Hyg. 2020;102:541–46.
- 31. Shafri A. The Association between Serum Vitamin D Levels and Helicobacter pylori Presence and Eradication. Nutrients. 2021;13(1):278.
- 32. Gobert AP, Wilson KT. Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection. Cell Mol Gastroenterol Hepatol. 2022;13(5):1347–63.
- 33. Mărginean MO, Mărginean CO, Meli LE, et al. The impact of host's genetic susceptibility on Helicobacter pylori infection in children. Medicine (Baltimore). 2017;96(30):e7612.
- 34. Pero R, Coretti L, Nigro E, et al . β-Defensins in the Fight against Helicobacter pylori. Molecules. 2017;22(3):424.
- 35. Wang TT, Nestel FP, Bourdeau V. Cutting Edge: 1,25 dihydroxyvitamin D3 is a direct inducer of antimic-robial peptide gene expression. J Immunol. 2004;173:2909-12.
- 36. Guo L, Chen, W, Huatuo ZH, et al. Helicobacter pylori induces increased expression of the vitamin d receptor in immune responses. Helicobacter. 2014;19(1):37–47.
- 37. Hosoda K, Shimomura H, Wanibuchi K, et al. Identi-fication and characterization of a vitamin D₃ decomposition product bactericidal against Helicobacter pylori. Sci Rep. 2015;5:8860.
- 38. Zhou A, Li L, Zhaom G, et al. Vitamin D3 Inhibits Helicobacter pylori Infection by Activating the VitD3/VDR-CAMP Pathway in Mice. Front Cell Infect Microbiol. 2020;23;10:566730.
- 39. Lai LH, Sung JJY. Helicobacter pylori and benign upper digestive disease. Best Pract Res Clin Gastroenterol. 2007;21:261-79.
- 40. Pachathundikandi SK, Müller A. Backert S. Inflammasome Activation by Helicobacter pylori and Its Implications for Persistence and Immunity. Curr Top Microbiol Immunol. 2016;397:117-31.
- 41. Serrano C, Wright HW, Bimczok D, et al. Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children. Mucosal Immunol. 2013;6(5):950-59.
- 42. Mullin GE, Dobs A. Vitamin D and its role in cancer and immunity: A prescription for sunlight. Nutr in Clinical Prac. 2007;22:305-22.
- 43. Tran LS, Chonwerawong M, Ferrero RC. Regulation and functions of inflammasome-mediated cytokines in Helicobacter pylori infection. Microbes Infect. 2017;19:449-58.
- 44. Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. A recent review on Vitamin D and immunoregulation. J Mol Med. 2010;88:441–50.
- 45. Martins DJ, Matos GCB, Loiola RSP, et al. Relationship of vitamin D receptor gene polymorphisms in Helicobacter pylori gastric patients. Clin Exp Gastroenterol. 2018;11:19–27.
ÇOCUKLARDA HELİKOBAKTER PYLORİ ENFEKSİYONU İLE PLAZMA 25 HİDROKSİ VİTAMİN D3 DÜZEYİ ARASINDAKİ İLİŞKİ
Year 2023,
Volume: 24 Issue: 3, 343 - 349, 13.07.2023
Gülseren Evirgen Şahin
,
Erhun Kasırga
,
Semin Ayhan
Abstract
AMAÇ: Helicobacter pylori (H.pylori) enfeksiyonunun şiddeti ve ilişkili hastalıkların varlığı konakçı, bakteriyel ve çevresel faktörlerden etkilenir. Bu çalışmada, H.pylori enfeksiyonu saptanan çocuklarda inflamatuar yanıtın düzenlenmesinde önemli rolü olan plazma 25 hidroksi vitamin D3 (vitD3) ile H.pylori enfeksiyonu arasındaki ilişkinin gösterilmesi amaçlanmıştır.
GEREÇ VE YÖNTEM: Mart 2010 - Mart 2011 tarihleri arasında Celal Bayar Üniversitesi Tıp Fakültesi gastroentroloji bölümünde dispeptik yakımalar ve medikal tedaviye dirençli demir eksikliği anemisi nedeni ile üst gastrointestinal endoskopi yapılan 3-18 yaş arası 201 hasta bu çalışmaya alındı. Biyopsi örneklerinin histopatolojik tanıları değerlendirildiğinde, H.pylori pozitif grupta 98, H.pylori negatif grupta 103 hasta vardı. Vitamin D3 düzeyi, H.pylori pozitif ve H.pylori negatif gruplarda karşılaştırıldı. Helicobacter pylori pozitif grupta ise gastrik mukozal aktivite ve inflamasyon şiddetinin derecesi ile vitD3 düzeyleri karşılaştırıldı.
BULGULAR: Helicobacter pylori pozitif hastaların 80'inde (81.6%), H.pylori negatif hastalarn 76'sında (73%) vitD3 düzeyleri düşüktü. Bu fark istatistiksel olarak anlamlı değildi (p>0.05). Helicobacter pylori pozitif ve negatif grupların plazma vitD3 düzeylerinin ortalama değeri sırasıyla 15.64±8.9 ng/mL ve 16.36±1.35 ng/mL idi. Gruplar arasındaki fark istatistiksel olarak anlamlı değildi (p>0.05). Helicobacter pylori pozitif ve negatif gruptaki hastalar, plazma vitD3 düzeyine göre eksiklik, şiddetli eksiklik, yetersizlik ve yetmezlik olarak dört farklı grupta sınıflandırıldığında ise H.pylori pozitif grupta vitD3 eksikliği H.pylori negatif gruba göre daha sıktı. Bu sonuç istatistiksel olarak anlamlıydı (p<0.05). Her iki grupta kronik inflamasyonun şiddeti ve doku H.pylori aktivitesi ortalama vitD3 düzeyi ile ters orantılı olarak arttığı görüldü (p<0.05).
SONUÇ: Çalışmamızın sonuçları bölgemizde çocuklarda vitD3 düşüklüğünün yaygın olduğunu göstermektedir. Vitamin D3 eksikliği H.pylori enfeksiyonu için risk faktörüdür. Bu çalışma H.pylori enfeksiyonunda vitD3'ün antibakteriyel etkiyi artırdığını ve inflamasyonun şiddetini azalttığını göstermektedir.
Project Number
Grant number. (332/140/1431)
References
- 1. Zhang S, Miller DD, Li W. Non-Musculoskeletal Benefits of Vitamin D beyond the Musculoskeletal System. Int J Mol Sci. 2021;22 (4):2128.
- 2. Bouillon R, Marcocci C, Carmeliet G, et al. Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions. Endocr Rev. 2019;40(4):1109–51.
- 3. Beckett E. More Than Bone Health: The Many Roles for Vitamin D. Nutrients. 2020;12(8):2388.
- 4. Vyas SP, Hansda AK, Kaplan MH, Goswami R. Calcitriol regulates the differentiation of IL-9-secreting Th9 cells by modulating the transcription factor PU.1. J Immunol. 2020;204(5):1201-13.
- 5. Wilkinson RJ, Liewelyn M, Toossi Z, et al. Influence of vitamin D deficiency and vitamin D polimorfisms on tuberculosis among Gujarati asians in west London: a case-control study. Lancet. 2000;355:618-21.
- 6. Gough ME, Graviss EdA, May EE. The dynamic immunomodulatory effects of vitamin D3 during Mycobacterium infection. Innate Immunity. 2017;23:(6)506–23.
- 7. Martineau AR, JolliffeDA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: individual participant data meta-analysis. Health Technol Assess. 2019;23:(2)1–44.
- 8. Laplana M, Royo JL, Fibla J. Vitamin D Receptor polymorphisms and risk of enveloped virus infection: A meta-analysis. Gene. 2018;678:384-94.
- 9. Ismailova A, White JH. Vitamin D, infections and immunity. Rev Endocr Metab Disord. 2022;23(2):265-77.
- 10. Hafeez AB, Jiang X, Bergen PJ, Zhu Y. Antimicrobial Peptides: An Update on Classifications and Databases. Int J Mol Sci. 2021;22(21):11691.
- 11. Wehkamp J, Schauber J, Stange EF. Defensins and cathelicidins in gastrointestinal infections. Curr Opin Gastroenterol. 2007;23:32–38.
- 12. Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin
D3. FASEB J. 2005;19(9):1067-77.
- 13. O’Neil DA, Cole, SP, Martin-Porter E, et al. Regulation of human β-defensins by gastric epithelial cells in response to infection with Helicobacter pylori or stimulation with interleukin-1. Infect Immun. 2000;9:5412–15.
- 14. Uehara N, Yagihashi, A Kondoh K, Tsuj N, et al. Human β-defensin-2. induction in Helicobacter infected gastric mucosal tissues: Antimicrobial effect of overexpression. J Med Microbiol. 2003;52:41–45.
- 15. Hu W, Zhang L, Li MX, et al. Vitamin D3 activates the autolysosomal degradation function against Helicobacter pylori through the PDIA3 receptor in gastric epithelial cells.. Autophagy.2019;15:707–25.
- 16. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81(3): 353–73.
- 17. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122(2):398-17.
- 18. Ailloud F, Didelot X, Woltemate S, et al. Within-host evolution of Helicobacter pylori shaped by niche-specific adaptation, intragastric migrations and selective sweeps. Nat Commun. 2019;10:2273.
- 19. Seo JH, Bortolin K, Jones NL. Review: Helicobacter pylori infection in children. Helicobacter. 2020;25(1): e12742.
- 20. Blosse A, Lehours P, Wilson KT, Alain P, Gobert AP. Helicobacter: Inflammation, immunology, and vaccines. Helicobacter. 2018;23:e12517.
- 21. Săsăran MO, Meliț LE, Dobru ED. MicroRNA Modulation of Host Immune Response and Inflammation Triggered by Helicobacter pylori. Int J Mol Sci. 2021;22(3):1406.
- 22. Doğan N, Çolak AA, Güden N, Üstüner F. Vitamin D deficiency in children in Aegean Region in Turkey. Cumhuriyet Medical Journal. 2015;37:17-22.
- 23. Özdemir AA, Gündemir YE, Küçük M et al. Vitamin D Deficiency in Pregnant Women and Their Infants. J Clin Res Pediatr Endocrinol. 2018;10(1):44–50.
- 24. Alpdemir M, Alpdemir MF. Vitamin D deficiency status in Turkey: A meta-analysis. Int J Med Biochem. 2019;(3):118-31.
- 25. Andersen R, Molgaard C, Skovgaard LT, et al. Teenage girls and elderly women living in northern europe have low winter vitamin D status. Eur J Clin Nutr. 2005;59:533-41.
- 26. Mutua AM, Nampijja M, Elliott AM, et al. Vitamin D status is not associated with cognitive or motor function in preschool Ugandan children. Nutrients. 2020;12:1662.
- 27. Ní Chaoimh C, McCarthy EK, Hourihane JO, et al. Low vitamin D deficiency in Irish toddlers despite northerly latitude and a high prevalence of inadequate intakes. Eur J Nutr. 2018;57:783–94.
- 28. Kawaura A, Takeda E, Tanida N, et al. Inhibitory effect of long term 1alpha-hydroxyvitamin D3 administration on Helicobacter pylori infection. J Clin Biochem Nutr. 2006;38:103–06.
- 29. Antico A, Tozzoli R, Giavarina D, Tonutti E, Bizzaro N. Hypovitaminosis D as predisposing factor for atrop-hic type A gastritis: a case-control study and review of the literature on the interaction of Vitamin D with
the immune system. Clin Rev Allergy Immunol. 2012;42:355–64.
- 30. Gao T, Zhao M, Zhang C, et al. Association of Helicobacter pylori infection with vitamine D deficiency in infants and toddlers. Am J Trop Med Hyg. 2020;102:541–46.
- 31. Shafri A. The Association between Serum Vitamin D Levels and Helicobacter pylori Presence and Eradication. Nutrients. 2021;13(1):278.
- 32. Gobert AP, Wilson KT. Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection. Cell Mol Gastroenterol Hepatol. 2022;13(5):1347–63.
- 33. Mărginean MO, Mărginean CO, Meli LE, et al. The impact of host's genetic susceptibility on Helicobacter pylori infection in children. Medicine (Baltimore). 2017;96(30):e7612.
- 34. Pero R, Coretti L, Nigro E, et al . β-Defensins in the Fight against Helicobacter pylori. Molecules. 2017;22(3):424.
- 35. Wang TT, Nestel FP, Bourdeau V. Cutting Edge: 1,25 dihydroxyvitamin D3 is a direct inducer of antimic-robial peptide gene expression. J Immunol. 2004;173:2909-12.
- 36. Guo L, Chen, W, Huatuo ZH, et al. Helicobacter pylori induces increased expression of the vitamin d receptor in immune responses. Helicobacter. 2014;19(1):37–47.
- 37. Hosoda K, Shimomura H, Wanibuchi K, et al. Identi-fication and characterization of a vitamin D₃ decomposition product bactericidal against Helicobacter pylori. Sci Rep. 2015;5:8860.
- 38. Zhou A, Li L, Zhaom G, et al. Vitamin D3 Inhibits Helicobacter pylori Infection by Activating the VitD3/VDR-CAMP Pathway in Mice. Front Cell Infect Microbiol. 2020;23;10:566730.
- 39. Lai LH, Sung JJY. Helicobacter pylori and benign upper digestive disease. Best Pract Res Clin Gastroenterol. 2007;21:261-79.
- 40. Pachathundikandi SK, Müller A. Backert S. Inflammasome Activation by Helicobacter pylori and Its Implications for Persistence and Immunity. Curr Top Microbiol Immunol. 2016;397:117-31.
- 41. Serrano C, Wright HW, Bimczok D, et al. Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children. Mucosal Immunol. 2013;6(5):950-59.
- 42. Mullin GE, Dobs A. Vitamin D and its role in cancer and immunity: A prescription for sunlight. Nutr in Clinical Prac. 2007;22:305-22.
- 43. Tran LS, Chonwerawong M, Ferrero RC. Regulation and functions of inflammasome-mediated cytokines in Helicobacter pylori infection. Microbes Infect. 2017;19:449-58.
- 44. Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. A recent review on Vitamin D and immunoregulation. J Mol Med. 2010;88:441–50.
- 45. Martins DJ, Matos GCB, Loiola RSP, et al. Relationship of vitamin D receptor gene polymorphisms in Helicobacter pylori gastric patients. Clin Exp Gastroenterol. 2018;11:19–27.