Chronic Ingestion of Low Doses of Cadmium Alters the Gut Microbiome and Immune Homeostasis for Enhanced Allergic Sensitization

Low doses of cadmium can be ingested due to its presence in contaminated water and its accumulation in leafy vegetables, fish and grains. Environment factors, including pollutants are believe to contribute to the increased incidence of allergy diseases. We addressed whether chronic ingestion of low doses of cadmium could impact allergic sensitization and thus, favor the development of allergic diseases. Conventional C57BL/6 mice given low doses of cadmium in the drinking water for 28 days exhibited a significant reduction of bacterial diversity, and an alteration of the Firmicutes to Bacteriodetes ratio. This treatment also activated both the canonical and the non-canonical NF-κB pathway and promoted proinflammatory cytokine and antimicrobial responses in the gut. The effects of cadmium were at least partially independent of the gut microbiome since germ-free C57BL/6 mice subjected to the same treatment developed the same profile of responses although at a lower degree. Finally, conventional mice chronically treated with low doses of cadmium developed higher antigen-specific IgE responses upon oral sensitization with OVA and cholera toxin as adjuvant. Furthermore, upon nasal antigen, cadmium-treated mice developed higher airway allergic response, which were characterized by the increased levels of IL-17 and Th1 responses control mice. In summary, ingestion of low doses of the environmental pollutant cadmium can be a major regulator of gut immune homeostasis and a cause for increased allergic responses at distant mucosal sites.