Involvement of Intestinal Mucosal Microbiota in Adenine-induced Liver Function Injury

Adenine is frequently utilized as a model medication for chronic renal disease. Adenine can affect organs other than the kidneys, including the heart and the intestine. The liver is a vital organ involved in the in vivo metabolism of adenine. Adenine may negatively impact liver function. Research indicated that adenine caused dysbiosis of the gut microbiota in mice. Investigations into the gut-liver axis have demonstrated a substantial association between drug-induced hepatic dysfunction and gut microbiota. Consequently, we delivered distinct dosages of adenine via gavage to mice to examine the correlation between adenine-induced liver impairment and gut microbiota dysbiosis. Mice were treated with low-dose adenine suspension (NLA), medium-dose adenine suspension (NMA), high-dose adenine suspension (NHA), and sterile water (NC) as a control. The results indicated that mice in the NLA, NMA, and NHA groups had decreased body weight and a reduction in liver index. Subsequent to adenine administration, the concentrations of AST, ALT, and LDH increased, whereas SDH levels decreased. As doses increased, liver function impairment and hepatic energy metabolism abnormalities aggravated. Adenine also damaged the colonic architecture in mice. Moreover, adenine modified the makeup and structure of the gut mucosal microbiota, enhancing specific bacterial genera and influencing the microbiota's energy metabolism-related functions. The results of our research established a correlation among certain bacteria, liver function injury, and hepatic energy metabolism. The gut mucosal microbiota was involved in adenine-induced liver injury and hepatic energy metabolism. These results can offer novel insights into the role of gut microbiota in drug-induced liver injury and provide specific guidelines for the modeling and therapeutic application of adenine.