Exposure to increasingly abundant environmental nickel (Ni) is unavoidable. The metal is well recognized as a common cause of allergic contact dermatitis (ACD), but overlooked systemic Ni allergy (SNAS) may also be associated with gastrointestinal (GI) symptoms. For the general population Ni-ACD affects about 3% of males and 15% of females, but it appears to be far more prevalent with excess adiposity and metabolic syndrome (MetS). Restriction of dietary Ni ameliorates dermal and systemic Ni allergy symptoms, and Ni associated metabolic perturbations may be mediated by a specific GI dysbiosis.
Plant-based food is the most common source of Ni exposure (https://www.fda.gov/media/77948/download). Nickel is notoriously associated with ACD, and SNAS may be associated with cutaneous, neurological and gastrointestinal symptoms. Nickel may also be associated with metabolic disruption of glucose homeostasis, and the transition metal promotes oxidative stress and inflammatory processes. Widespread excessive adiposity and MetS are chronic inflammatory conditions, and Ni allergy is reported to be much more common among obese women with MetS.
Perimenopausal women (n=72) enrolled in a preventive health program were screened for Ni-ACD (NiSO4 patch test) and MetS. Ni-ACD was detected in 59.7% of obese women with MetS (body fat 45 +/- 7%) compared to 12.5% for the general female population. Adherence to a low-Ni, normocaloric diet for 6 months was associated with significant reductions in BMI (-4 units), body fat (-5%), and waist circumference (-5 in.). The dietary intervention study (n=24) did not incorporate appropriate control groups, but other studies have documented the efficacy of Ni restricted diets for Ni-ACD and SNAS patients.
That Ni allergy may be more prevalent with obesity and MetS was confirmed in a subsequent observational study of obese outpatients (n=1,128, 91% female). Forty-one% of the obese patients were positive for Ni-ACD. Compared to the non-allergic cohort, Ni allergy was associated with significantly higher BMI, worse body composition, lower levels of insulin-like growth factor, and higher fasting insulin, HOMA-IR, and CRP. It should be noted that all subjects were Ni allergy suspect.
For sensitized individuals, Ni ingestion may induce IBS-like gastrointestinal (GI) symptoms, and preliminary evidence for a Ni-ACD dysbiosis has been presented. Analysis of fecal bacteria (culturomics) for lean and obese women indicated different bacterial composition for Ni allergic cohorts compared to non-allergic controls. Moreover, microbial resistance to Ni was associated Ni allergy. In culture, bacterial viability with higher concentrations of added NiSO4 was exhibited for the allergic cohorts, and tolerance to a very high, non-physiological Ni concentration was exhibited only for severely allergic obese subjects. Microbial resistance to Ni with sensitization is intriguing, and more expansive investigations incorporating molecular methodologies might identify and characterize a “Ni dysbiosis.”
About ninety percent of diet-derived Ni is unabsorbed and available to affect the microbial community and the mucosal barrier. Microbial-host crosstalk with specialized mucosal cells regulates glucose hemostasis, adipocyte inflammation, appetite regulation and endothelial cell permeability. Additional studies are needed to unravel the nature of the newly discovered relationships among Ni sensitization and exposure, inflammation, obesity, MetS and the GI microbiota.