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

LaNiO₃ exhibits outstanding physical and chemical properties, demonstrating promising potential for regulating immune responses in disease contexts. We discovered that LaNiO₃ promotes autophagy and immune suppression. After oral administration of LaNiO₃ 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 LaNiO₃ to mice over 7 days, both La and Ni primarily accumulated in the gut. LaNiO₃ suppressed the immune responses through down-regulation of TNF-α and IL-6. Furthermore, LaNiO₃ increased the abundance of intestinal microbiota and metabolites, with up-regulated microbiota such as <i>Helicobacter</i>, <i>Prevotellaceae</i>, <i>Pseudomonas</i>, <i>Bacteroides</i>, <i>Clostridium sensu stricto 1</i>, <i>Ruminiclostridium</i>, 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, LaNiO₃ can induce autophagy, including up-regulation of LC3A/B I/II and down-regulation of p62. In summary, oral exposure to LaNiO₃ in mice regulates the immune system, modulates gut flora, and induces intestinal autophagy. This study provides meaningful data for the safety of LaNiO₃ oral application and formulation.