Higher incidence of zinc and nickel hypersensitivity in patients with irritable bowel syndrome Original paper

What was studied?

This study investigated the higher incidence of zinc and nickel hypersensitivity in patients with irritable bowel syndrome (IBS), directly exploring how metal-induced immune activation might contribute to low-grade mucosal inflammation. The focus keyphrase zinc and nickel hypersensitivity in IBS appears here because the researchers proposed that immune responses to trace metal ions released from dental materials could trigger or exacerbate IBS symptoms. The investigation assessed whether IBS patients exhibit elevated T-cell–mediated hypersensitivity to commonly used dental metals—zinc, nickel, gold, and palladium—using the drug-induced lymphocyte stimulation test (DLST). The study leveraged both quantitative stimulation indices and sensitization prevalence to determine whether metal hypersensitivity might serve as a microbial-relevant immune signature, potentially connecting environmental exposures to mucosal immune dysfunction in IBS.

Who was studied?

The study examined 147 Japanese adults diagnosed with IBS, classified by Rome IV criteria into IBS-D, IBS-C, IBS-M, and IBS-U subtypes. These individuals represented a clinically diverse group with chronic abdominal pain and altered bowel habits. A comparison group of 22 healthy controls with no IBS symptoms established baseline sensitization patterns. All participants underwent DLST testing to quantify lymphocyte activation in response to zinc, nickel, gold, and palladium. This population design enabled the researchers to distinguish disease-specific hypersensitivity patterns from background sensitization rates in the general population, illustrating how IBS patients may uniquely respond immunologically to metal exposures encountered through dental materials and dietary sources.

Most important findings

A strikingly higher proportion of IBS patients exhibited sensitization to at least one dental metal (56.5%) compared with healthy controls (31.8%), as shown in the sensitization bar chart. The most significant differences involved zinc and nickel. None of the healthy controls exhibited zinc hypersensitivity, whereas 36.4% of IBS patients did, with markedly elevated stimulation indices (mean SI, 352 vs. 119). Nickel hypersensitivity also differed significantly, affecting 39.6% of IBS patients versus 21.1% of controls, accompanied by higher mean SI values. Figures on page 3 visually depict these shifts with clearly elevated beeswarm distributions. No meaningful differences were observed for gold or palladium, and hypersensitivity rates did not vary across IBS subtypes. These results map closely to established immune pathways: zinc elicits CD8-dominant lichenoid reactions, while nickel promotes IL-17A-producing CD4+ T-cell expansion—both mechanisms implicated in mucosal immune dysregulation and gut–neuron signaling relevant to IBS.

Key implications

This study suggests that zinc and nickel hypersensitivity may contribute to the characteristic low-grade immune activation seen in a subset of IBS patients. Because many common foods are rich in these metals and dental alloys can release trace ions chronically, hypersensitive individuals may experience ongoing T-cell activation that amplifies visceral pain pathways and mucosal inflammation. The findings support further investigation of dietary metal load, dental materials, and immune profiling as potential components of microbiome-informed IBS management strategies. Although preliminary, the work highlights environmental–immune interactions that might modify the intestinal milieu, influence microbial composition, and shape patient-specific symptom patterns.

Citation

Kageyama Y, Aida K, Kawauchi K, Morimoto M, Akiyama T, Nakamura T. Higher incidence of zinc and nickel hypersensitivity in patients with irritable bowel syndrome. Immun Inflamm Dis. 2019;7(3):304-307. doi:10.1002/iid3.274 IID3-7-304