The influence of nickel on intestinal microbiota disturbances

Jessica Świerc, Sylwia Drzymała, Dagmara Woźniak, Sławomira Drzymała-Czyż


Introduction: Over the last decade, there has been an increased interest in the role of nickel as a cause of allergic reactions and as an element affecting the intestinal microbiota. Its presence can cause dysbiosis, i.e., an increase in the number of harmful microorganisms at the expense of probiotic bacteria. The disturbed microbiota affects the organism’s metabolism and increases the risk of developing certain diseases. This study aims to analyze the available scientific literature on nickel and its effect on the disturbances in the intestinal microbiota.

Materials and methods: The PubMed database and the Cochrane Library were used to find scientific articles with the following combinations of keywords: ‘nickel’, ‘nickel and microbiota’, ‘nickel and allergy’, ‘nickel and health’, ‘microbiota’, and ‘microbiota disturbances’. Scientific publications from the last 20 years were analyzed.

Results: Nickel is an essential element for certain biochemical reactions that allow microorganisms (both beneficial and harmful) to grow and develop. Some strains of bacteria seem to have the ability to reduce the host’s exposure to this heavy metal. Excess nickel intake contributes to the disturbance of the proper composition of intestinal microflora, especially in patients diagnosed with systemic nickel allergy syndrome. This may have adverse health effects, possibly contributing to obesity.

Conclusions: The wide use of nickel in consumer products, as well as its widespread presence in water and food, increases the probability of human contact with this metal. Further research on the influence of nickel on the human body and its microbiota should be conducted.


nickel; microbiota; human health; dysbiosis; diet

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Ahlström MG, Thyssen JP, Wennervaldt M, Menné T, Johansen JD. Nickel allergy and allergic contact dermatitis: A clinical review of immunology, epidemiology, exposure, and treatment. Contact Dermatitis 2019;81(4):227-41. doi: 10.1111/cod.13327.

Woźniak D, Cichy W, Przysławski J, Drzymała-Czyż S. The role of microbiota and ente-roendocrine cells in maintaining homeostasis in the human digestive tract. Adv Med Sci 2021;66(2):284-92. doi: 10.1016/j. advms.2021.05.003.

Madison A, Kiecolt-Glaser JK. Stress, depression, diet, and the gut microbiota: human-bacteria interactions at the core of psychoneuroimmunology and nutrition. Curr Opin Behav Sci 2019;28:105-10. doi: 10.1016/j. cobeha.2019.01.011.

Tramontana M, Bianchi L, Hansel K, Agostinelli D, Stingeni L. Nickel allergy: epidemio-logy, pathomechanism, clinical patterns, treatment and prevention programs. Endocr Metab Immune Disord Drug Targets 2020;20(7):992-1002. doi: 10.2174/1871530320666200128141900.

Denkhaus E, Salnikow K. Nickel essentiality, toxicity, and carcinogenicity. Crit Rev On-col Hematol 2002;42(1):35-56. doi: 10.1016/s1040- 8428(01)00214-1.

Zambelli B, Ciurli S. Nickel and human health. Met Ions Life Sci 2013;13:321- 57. doi: 10.1007/978-94-007-7500-8_10.

Zhao J, Shi X, Castranova V, Ding M. Occupational toxicology of nickel and nickel com-pounds. J Environ Pathol Toxicol Oncol 2009;28(3):177-208. doi: 10.1615/jenvironpatholtoxicoloncol.v28.i3.10.

Guo H, Liu H, Wu H, Cui H, Fang J, Zuo Z, et al. Nickel carcinogenesis mechanism: DNA damage. Int J Mol Sci 2019;20(19):4690. doi: 10.3390/ ijms20194690.

Zambelli B, Uversky VN, Ciurli S. Nickel impact on human health: An intrinsic disorder perspective. Biochim Biophys Acta 2016;1864(12):1714-31. doi: 10.1016/j.bbapap.2016.09.008.

Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999;37(2):279-92. doi: 10.1081/ clt-100102426.

Zdrojewicz Z, Popowicz E, Winiarski J. Nikiel – rola w organizmie człowieka i działanie toksyczne. Pol Merkur Lekarski 2016;41(242):115-8.

Ringborg E, Lidén C, Julander A. Nickel on the market: a baseline survey of articles in ‘prolonged contact’ with skin. Contact Dermatitis 2016;75(2):77- 81. doi: 10.1111/cod.12602.

Bencko V, Wagner V, Wagnerová M, Reichrtová E. Immuno-biochemical findings in groups of individuals occupationally and nonoccupationally exposed to emissions contai-ning nickel and cobalt. J Hyg Epidemiol Microbiol Immunol 1983;27(4):387-94.

Shirakawa T, Kusaka Y, Morimoto K. Specific IgE antibodies to nickel in workers with known reactivity to cobalt. Clin Exp Allergy 1992;22(2):213- 8. doi: 10.1111/j.1365-2222.1992.tb03075.x.

Kumar V, Mishra RK, Kaur G, Dutta D. Cobalt and nickel impair DNA metabolism by the oxidative stress independent pathway. Metallomics 2017;9(11):1596-609. doi: 10.1039/c7mt00231a.

Łańczak A, Choręziak A, Płocka M, Sadowska-Przytocka A, Czarnecka- -Operacz M, Adamski Z, et al. Nickel-free environment – dreams vs. reality: Everyday utilities as a so-urce of nickel and cobalt for patients sensitized to these metals. JMS 2019;88(3):150-5. doi: 10.20883/jms.357.

Wojciechowska M, Kołodziejczyk J, Gocki J, Bartuzi Z. Nadwrażliwość na nikiel. Alerg Astma Immunol 2008;13(3):136-40.

Genchi G, Carocci A, Lauria G, Sinicropi MS, Catalano A. Nickel: human health and environmental toxicology. Int J Environ Res Public Health 2020;17(3):679. doi: 10.3390/ijerph17030679.

Guarneri F, Costa C, Cannavò SP, Catania S, Bua GD, Fenga C, et al. Release of nickel and chromium in common foods during cooking in 18/10 (grade 316) stainless steel pots. Contact Dermatitis 2017;76(1):40-8. doi: 10.1111/ cod.12692.

EFSA Panel on Contaminants in the Food Chain (CONTAM). Scientific Opinion on the risks to public health related to the presence of nickel in food and drinking water. EFSA J 2015;13(2):4002.

EFSA Panel on Contaminants in the Food Chain (CONTAM). Update of the risk as-sessment of nickel in food and drinking water. EFSA J 2020;18(11):6268. doi: 10.2903/j.efsa.2020.6268.

Jensen CS, Menné T, Johansen JD. Systemic contact dermatitis after oral exposure to nickel: a review with a modified meta-analysis. Contact Dermatitis 2006;54(2):79-86. doi: 10.1111/j.0105-1873.2006.00773.x.

Ricciardi L, Arena A, Arena E, Zambito M, Ingrassia A, Valenti G, et al. Systemic nickel allergy syndrome: epidemiological data from four Italian allergy units. Int J Immunopathol Pharmacol 2014;27(1):131-6. doi: 10.1177/039463201402700118.

Bibbò S, Ianiro G, Giorgio V, Scaldaferri F, Masucci L, Gasbarrini A, et al. The role of diet on gut microbiota composition. Eur Rev Med Pharmacol Sci 2016;20(22):4742-9.

Stinson LF, Boyce MC, Payne MS, Keelan JA. The not-so-sterile womb: evidence that the human fetus is exposed to bacteria prior to birth. Front Microbiol 2019;10:1124. doi: 10.3389/fmicb.2019.01124.

Zoetendal EG, Vaughan EE, de Vos WM. A microbial world within us. Mol Microbiol 2006;59(6):1639-50. doi: 10.1111/j.1365-2958.2006.05056.x.

Barczyńska R, Śliżewska K, Libudzisz Z, Litwin M. Rola mikrobioty jelit w utrzymaniu prawidłowej masy ciała. Stand Med, Pediatr 2013;1:55-62.

Wang H X, Wang Y P. Gut m icrobiota-brain a xis. C hin Med J ( Engl) 2016;129(19):2373-80. doi: 10.4103/0366-6999.190667.

Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environ-ment, diet, and diseases. Microorganisms 2019;7(1):14. doi: 10.3390/microorganisms7010014.

Odamaki T, Kato K, Sugahara H, Hashikura N, Takahashi S, Xiao JZ, et al. Age-related changes in gut microbiota composition from newborn to centenarian: A cross-sectional study. BMC Microbiol 2016;16(90):1-12. doi: 10.1186/s12866-016-0708-5.

Riva A, Borgo F, Lassandro C, Verduci E, Morace G, Borghi E, et al. Pediatric obesity is associated with an altered gut microbiota and discordant shifts in Firmicutes populations. Environ Microbiol 2017;19(1):95-105. doi: 10.1111/1462-2920.13463.

Gregorczyk-Maślanka K, Kurzawa R. Mikrobiota organizmu ludzkiego i jej wpływ na ho-meostazę immunologiczną – część I. Alerg Astma Immun 2016;21(3):146-50.

Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol 2015;31(1):69-75. doi: 10.1097/ MOG.0000000000000139.

Drzymała-Czyż S, Banasiewicz T, Biczysko M, Walkowiak J. Maślany w nieswoistych za-paleniach jelit. Fam Med Primary Care Rev 2011;13(2):305-7.

Książek EE, Chęcińska-Maciejewska Z, Grochowska A, Krauss H. Czynniki żywieniowe wpływające na kształtowanie mikrobioty przewodu pokarmowego. In: Krauss H, editor. Fizjologia żywienia. Warszawa: Wydawnictwo Lekarskie PZWL; 2019. p. 231-49.

Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A. Gut microbio-ta in autism and mood disorders. World J Gastroenterol 2016;22(1):361-8. doi: 10.3748/wjg.v22.i1.361.

Rosenfeld CS. Gut dysbiosis in animals due to environmental chemical exposures. Front Cell Infect Microbiol 2017;7:396. doi: 10.3389/ fcimb.2017.00396.

Turroni F, Foroni E, Pizzetti P, Giubellini V, Ribbera A, Merusi P, et al. Exploring the diversity of the bifidobacterial population in the human intestinal tract. Appl Environ Mi-crobiol 2009;75(6):1534-45. doi: 10.1128/ AEM.02216-08.

Richardson JB, Dancy BCR, Horton CL, Lee YS, Madejczyk MS, Xu ZZ, et al. Exposure to toxic metals triggers unique responses from the rat gut microbiota. Sci Rep 2018;8(1):6578. doi: 10.1038/s41598-018-24931-w.

Lusi EA, Santino I, Petrucca A, Zollo V, Magri F, O’Shea D, et al. The human nickel mi-crobiome and its relationship to allergy and overweight in women. bioRxiv 2019;546739. doi: 10.1101/546739.

Li X, Brejnrod AD, Ernst M, Rykær M, Herschend J, Olsen NMC, et al. Heavy metal exposure causes changes in the metabolic health-associated gut microbiome and metabo-lites. Environ Int 2019;126:454-67. doi: 10.1016/j. envint.2019.02.048.

Lu K, Abo RP, Schlieper KA, Graffam ME, Levine S, Wishnok JS, et al. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metageno-mics and metabolomics analysis. Environ Health Perspect 2014;122(3):284-91. doi: 10.1289/ehp.1307429.

Zhang S, Jin Y, Zeng Z, Liu Z, Fu Z. Subchronic exposure of mice to cadmium perturbs their hepatic energy metabolism and gut microbiome. Chem Res Toxicol 2015;28(10):2000-9. doi: 10.1021/acs.chemrestox.5b00237.

Liu Y, Li Y, Liu K, Shen J. Exposing to cadmium stress cause profound toxic effect on mi-crobiota of the mice intestinal tract. PLoS One 2014;9(2):e85323. doi: 10.1371/journal.pone.0085323.

Wu B, Cui H, Peng X, Pan K, Fang J, Zuo Z, et al. Toxicological effects of dietary nickel chloride on intestinal microbiota. Ecotoxicol Environ Saf 2014;109:70-6. doi: 10.1016/j.ecoenv.2014.08.002.

Li Y, Liu K, Shen J, Liu Y. Wheat bran intake can attenuate chronic cadmium toxicity in mice gut microbiota. Food Funct 2016;8(7):3524-30. doi: 10.1039/C6FO00233A.

Breton J, Massart S, Vandamme P, De Brandt E, Pot B, Foligné B. Ecotoxicology inside the gut: impact of heavy metals on the mouse microbiome. BMC Pharmacol Toxicol 2013;14:62. doi: 10.1186/2050-6511-14-62.

Zhou X, Li J, Sun JL. Oral nickel changes of intestinal microflora in mice. Curr Microbiol 2019;76(5):590-6. doi: 10.1007/s00284-019-01664-1.

Rizzi A, Nucera E, Laterza L, Gaetani E, Valenza V, Corbo GM, et al. Irritable bowel syn-drome and nickel allergy: what is the role of the low nickel diet? J Neurogastroenterol Motil 2017;23(1):101-8. doi: 10.5056/jnm16027.

Di Gioacchino M, Ricciardi L, De Pità O, Minelli M, Patella V, Voltolini S, et al. Nickel oral hyposensitization in patients with systemic nickel allergy syndrome. Ann Med 2014;46(1):31-7. doi: 10.3109/07853890.2013.861158.

Minelli M, Schiavino D, Musca F, Bruno ME, Falagiani P, Mistrello G, et al. Oral hypo-sensitization to nickel induces clinical improvement and a decrease in TH1 and TH2 cy-tokines in patients with systemic nickel allergy syndrome. Int J Immunopathol Pharmacol 2010;23(1):193-201. doi: 10.1177/039463201002300117.

Randazzo CL, Pino A, Ricciardi L, Romano C, Comito D, Arena E, et al. Probiotic sup-plementation in systemic nickel allergy syndrome patients: study of its effects on lactic acid bacteria population and on clinical symptoms. J Appl Microbiol 2015;118(1):202-11. doi: 10.1111/jam.12685.

Camilo V, Sugiyama T, Touati E. Pathogenesis of Helicobacter pylori infection. Helico-bacter 2017;22 Suppl 1:e12405. doi: 10.1111/hel.12405.

Drzymała-Czyż S, Kwiecień J, Pogorzelski A, Rachel M, Banasiewicz T, Pławski A, et al. Prevalence of Helicobacter pylori infection in patients with cystic fibrosis. J Cyst Fibros 2013;12(6):761-5. doi: 10.1016/j. jcf.2013.01.004.

Benoit SL, Miller EF, Maier RJ. Helicobacter pylori stores nickel to aid its host coloniza-tion. Infect Immun 2013;81(2):580-4. doi: 10.1128/ IAI.00858-12.

Campanale M, Nucera E, Ojetti V, Cesario V, Di Rienzo TA, D’Angelo G, et al. Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study. Dig Dis Sci 2014;59(8):1851-5. doi: 10.1007/s10620-014-3060-3.

Abenavoli L, Scarpellini E, Colica C, Boccuto L, Salehi B, Sharifi-Rad J, et al. Gut micro-biota and obesity: A role for probiotics. Nutrients 2019;11(11):2690. doi: 10.3390/nu11112690.

Lusi EA, Di Ciommo VM, Patrissi T, Guarascio P. High prevalence of nickel allergy in an overweight female population: a pilot observational analysis. PLoS One 2015;10(3):e0123265. doi: 10.1371/journal.pone.0123265.

Cerdó T, García-Santos JA, Bermúdez MG, Campoy C. The role of probiotics and prebio-tics in the prevention and treatment of obesity. Nutrients 2019;11(3):635. doi: 10.3390/nu11030635.

Luoto R, Kalliomäki M, Laitinen K, Isolauri E. The impact of perinatal probiotic interven-tion on the development of overweight and obesity: follow-up study from birth to 10 ye-ars. Int J Obes (Lond) 2010;34(10):1531- 7. doi: 10.1038/ijo.2010.50.

Sanchis-Chordà J, Del Pulgar EMG, Carrasco-Luna J, Benítez-Páez A, Sanz Y, Codoñer-Franch P. Bifidobacterium pseudocatenulatum CECT 7765 supplementation improves inflammatory status in insulin-resistant obese children. Eur J Nutr 2019;58(7):2789-800. doi: 10.1007/s00394-018-1828-5.

Jung S, Lee YJ, Kim M, Kim M, Kwak JH, Lee JW, et al. Supplementation with two pro-biotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, redu-ced body adiposity and Lp-PLA2 activity in overweight subjects. J Funct Foods 2015;19:744-52. doi: 10.1016/j. jff.2015.10.006.

Gomes AC, de Sousa RG, Botelho PB, Gomes TL, Prada PO, Mota JF. The additional ef-fects of a probiotic mix on abdominal adiposity and antioxidant status: A double-blind, randomized trial. Obesity (Silver Spring) 2017;25(1):30-8. doi: 10.1002/oby.21671.

Watanabe M, Masieri S, Costantini D, Tozzi R, De Giorgi F, Gangitano E, et al. Overweight and obese patients with nickel allergy have a worse metabolic profile compared to weight matched non-allergic individuals. PLoS One 2018;13(8):e0202683. doi: 10.1371/journal.pone.0202683.


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