Bacillus amyloliquefaciens K309 promotes copper detoxification in vivo through concerted biosorption and microbial metabolism.

Prolonged consumption of diets high in copper (Cu) leads to multiorgan copper accumulation in fattening pigs, resulting in a year-on-year increase in the incidence of clinical copper poisoning and posing a potential risk to human food safety. Gut probiotics have demonstrated potential for preventing and treating copper toxicity because of their ability to chelate heavy metal ions and maintain metabolic homeostasis. However, the mechanism of action remains poorly understood. Our study identified a strain of Bacillus amyloliquefaciens K309 isolated from pigs with significant copper ion absorption capacity. Supplementation with B. amyloliquefaciens K309 reduced blood and intestinal copper levels in weaned piglets but increased fecal copper excretion, thus alleviating intestinal barrier damage. Further investigations revealed that B. amyloliquefaciens K309 intervention promoted hepatic bile secretion and suppressed UCP2 expression. Moreover, luteolin, which was produced by the gut microbiota enriched after B. amyloliquefaciens K309 intervention, also alleviated symptoms in copper-intoxicated mice. Mechanistically, luteolin alleviates high copper-induced hepatocyte apoptosis by promoting the targeting of K48-linked polyubiquitination degradation of UCP2 by ASB4. These findings establish B. amyloliquefaciens K309 as a key microorganism for preventing and treating copper toxicity, revealing its dual novel functions of biosorption and metabolic regulation previously unreported for this strain.