H. pylori and the Nickel Connection

Almost half of the world’s population has Helicobacter pylori.

What is Helicobacter Pylori?

H. pylori is a type of gram-negative bacteria that enters the body and causes infections of the digestive system. The bacteria are spiral and live in the mucus layer of the stomach. When H. pylori inhabit the digestive system for a long time, it causes ulcers in the stomach or small intestine. Stomach cancer can also develop in some people due to H. pylori infection (3).

How do H. pylori survive in the human stomach for a long time?

The persistent existence of H. pylori is partly due to two enzymes that contain nickel. These enzymes, urease and hydrogenase, are secreted by H. pylori. The enzyme urease creates resistance against gastric acid of the stomach, while hydrogenase helps in the colonization of bacteria because it allows the bacteria to breathe in the presence of hydrogen (H2) in the mucus lining of the stomach (4).

How do H. pylori store nickel?

In H. pylori, the metabolism and trafficking of nickel is a complex process. H. pylori is aided by two nickel storage proteins known as Hpn and Hpnl (5). A constant and regulated supply of nickel is required for the survival of H. pylori in the acidic environment of the stomach. Increased storage of nickel can result in the generation of reactive oxygen species (6).

The tolerance of H. pylori to cobalt, nickel and cadmium decreases in the case of Hpn and Hpnl deletion (8). Under the acidic condition, Hpn and Hpnl release nickel. This shows that when there is a need to maintain the pH for urease activity, bacterial cells get the nickel supply from these proteins (10,11).

How does a low-nickel diet help in the treatment of H. pylori?

Typically, antibiotics are prescribed along with proton pump inhibitors for the treatment of H. pylori infection. However, recent research has shown that even treatment with antibiotics fails to eradicate H. pylori in 20% of people (12).

Since the survival of H. pylori is dependent on nickel-containing enzymes urease and hydrogenase, a substantial increase in the eradication of H. pylori infection can be achieved when a low-nickel diet is followed. The low-nickel diet reduces the urease activity of H. pylori. This increases the exposure of bacterium to gastric acid and enhances the susceptibility of bacteria to antibiotics (13).


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9. Mobley HL, Garner RM, Chippendale GR, Gilbert JV, Kane AV, Plaut AG. Role of Hpn and NixA of Helicobacter pylori in susceptibility and resistance to bismuth and other metal ions. Helicobacter. 1999 Sep;4(3):162–9. 

10. Ge R, Watt RM, Sun X, Tanner JA, He Q-Y, Huang J-D, et al. Expression and characterization of a histidine-rich protein, Hpn: potential for Ni2+ storage in Helicobacter pylori. Biochem J. 2006 Jan 1;393(Pt 1):285–93. 

11. Zeng Y-B, Zhang D-M, Li H, Sun H. Binding of Ni2+ to a histidine- and glutamine-rich protein, Hpn-like. J Biol Inorg Chem. 2008 Sep;13(7):1121–31. 

12. Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007 Jun;56(6):772–81. 

13. 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 Aug;59(8):1851–5.