Oral exposure to LaNiO(3) regulates the immune system, modulates gut flora, and induces intestinal autophagy in mice.

LaNiO(3) exhibits outstanding physical and chemical properties, demonstrating promising potential for regulating immune responses in disease contexts. We discovered that LaNiO(3) promotes autophagy and immune suppression. After oral administration of LaNiO(3) in mice (7 days post single exposure at a dose of 10 mg kg(-1)), techniques from metallomics, microbiology, metabolomics, and molecular biology are used to evaluate toxicity, elemental distribution, intestinal autophagy, immune suppression, and effects on intestinal microbiota and metabolites. The results indicate that following a single oral administration of 10 mg per kg LaNiO(3) to mice over 7 days, both La and Ni primarily accumulated in the gut. LaNiO(3) suppressed the immune responses through down-regulation of TNF-α and IL-6. Furthermore, LaNiO(3) increased the abundance of intestinal microbiota and metabolites, with up-regulated microbiota such as Helicobacter, Prevotellaceae, Pseudomonas, Bacteroides, Clostridium sensu stricto 1, Ruminiclostridium, and so on, as well as amino acids and bile acid metabolites such as glutamate, lysine, l-citrulline, and 7α-hydroxy-4-cholesten-3-one. Then, LaNiO(3) can induce autophagy, including up-regulation of LC3A/B I/II and down-regulation of p62. In summary, oral exposure to LaNiO(3) in mice regulates the immune system, modulates gut flora, and induces intestinal autophagy. This study provides meaningful data for the safety of LaNiO(3) oral application and formulation.