Nickel exposure induces gut microbiome disorder and serum uric acid elevation Original paper

What was studied?

Nickel exposure induces gut microbiome disorder, and serum uric acid elevation was investigated to understand how chronic nickel exposure affects hyperuricemia through gut microbial and metabolic alterations in humans and mice. The study integrated human occupational exposure data, targeted microbial profiling, and metabolomic analyses to determine mechanistic links between nickel-associated dysbiosis, disrupted intestinal purine catabolism, and elevated serum uric acid. The research combined 16S rRNA sequencing and LC-MS/MS metabolomics to map microbial taxa changes and purine pathway perturbations, while mouse models validated causality and inflammatory consequences. The work also examined correlations between microbial shifts, bile acid metabolism, oxidative stress markers, and inflammation, revealing a multisystem disruption connecting heavy metal exposure to uric acid accumulation.

Who was studied?

A total of 109 human participants from an occupational cohort in Jinchang, China were examined, including 92 nickel-exposed workers and 17 unexposed controls. Inclusion criteria excluded kidney, liver, thyroid, or intestinal disease, ensuring uric acid elevations reflected exposure-related mechanisms rather than comorbidities. Fecal and serum samples were collected for microbiome and metabolomic profiling. Complementary mouse experiments used female Kun Ming mice receiving oral nickel chloride for 35 days to assess causal relationships between nickel exposure, microbiome disruption, purine metabolism, and systemic inflammation. Both populations showed consistent patterns, strengthening translational relevance.

Most important findings

Nickel exposure induced clear microbiome alterations strongly associated with disrupted purine metabolism and higher serum uric acid. Key purine-degrading taxa—including Lactobacillus, Lachnospiraceae_unclassified, and Blautia—were significantly reduced. These microbes normally degrade uric acid or reduce purine absorption, and their depletion paralleled elevated fecal purines and impaired intestinal purine breakdown. Pathogenic or inflammation-associated taxa, such as Parabacteroides, Escherichia-Shigella, Alistipes, and Mycoplasma, were enriched, contributing to intestinal inflammation and increased permeability. Metabolomic analyses showed elevated fecal adenine, guanine, inosine, and hypoxanthine, while serum uric acid was significantly higher. Mouse data confirmed increased serum uric acid, heightened pro-inflammatory cytokines, oxidative stress markers, and similar microbiome disruptions. Together, these findings identify a gut-driven mechanism in which nickel suppresses purine degradation, enhances systemic absorption of purines, and fosters inflammatory conditions that exacerbate uric acid accumulation.

Key implications

This study provides strong evidence that nickel-induced hyperuricemia is mediated not by impaired renal excretion alone but by microbiome-driven metabolic dysfunction. Heavy metal exposure disrupts the intestinal ecosystem, reduces key uricolytic microbes, suppresses purine catabolism, increases gut permeability, and intensifies inflammation. These findings expand the known environmental determinants of hyperuricemia and spotlight gut microbiome signatures—particularly reductions in Lactobacillus, Blautia, and Lachnospiraceae_unclassified and enrichment of inflammatory taxa—as potential biomarkers. Clinically, microbiome-targeted interventions may represent future therapeutic strategies for heavy-metal–associated hyperuricemia.

Citation

Yang J, Feng P, Ling Z, et al. Nickel exposure induces gut microbiome disorder and serum uric acid elevation. Environmental Pollution. 2023;324:121349. doi:10.1016/j.envpol.2023.121349