Investigation of the Role of Gut Microbiota in the Detoxification of Aristolochic Acids

Aristolochic acid nephropathy (AAN) is a serious kidney disease that gained prominence in the 1990s when cases in Belgium were linked to slimming pills containing Aristolochia fangchi, resulting in acute kidney injury. Research identified aristolochic acids (AAs) as the primary cause, raising awareness of their risks. Balkan endemic nephropathy (BEN) is a chronic kidney disease affecting rural communities along the Danube River, with prolonged exposure to AAs in agricultural crops potentially contributing to its development. AAs, derived from plants in the Aristolochiaceae family, are carcinogenic due to their ability to form DNA adducts, leading to mutations and tumor formation. However, AAs can be converted into non-toxic metabolites through biological processes to reduce their toxicity. Gut microbiota comprises a diverse array of microorganisms in the gastrointestinal tract that play vital roles in human health. Probiotics, a specific group of beneficial microorganisms, can positively influence both the composition and function of gut microbiota. Recent studies have shown that gut microbiota can also metabolize certain carcinogens, including aflatoxins. To gain a clearer understanding of the nephrotoxicity and carcinogenicity of AAs in the human body, it is crucial to know the relationship between gut microbiota and AAs. Currently, the biodegradation abilities of gut microbiota to reduce AA-I in culture medium were investigated on the laboratory scale. The results indicated that gut microbiota could eliminate over 90% of aristolochic acid I (AA-I) after a 3-day incubation period. Commonly utilized probiotics can also metabolize AA-I in the short term. The degradation products have been identified as aristolactam I (AL-I) and aristolic acid I (AR-I), both of which are metabolites of AA-I. On the other hand, AA-I was administered to mice that had been treated with several antibiotics to eliminate the gut microflora, and the preliminary results showed that mice receiving antibiotics treatment exhibited a higher formation of DNA adducts in target organs associated with AA-I. Additionally, more metabolites can be found in the feces of the normal mice group compared to those treated with antibiotics. The results indicate that AA-I can be converted into non-toxic metabolites that are excreted from the body through feces, thereby reducing the toxicity of AA-I.