Investigation on Patulin biotransformation in Zebrafish and its toxicological function evaluation

Area of Science:

• Toxicology
• Metabolomics
• Microbiology

Background:

• Patulin (PAT) is a significant mycotoxin with limited known in vivo biotransformation and toxicological data.
• Understanding PAT's effects is crucial for human and animal health risk assessment.

Purpose of the Study:

• To investigate the in vivo biotransformation of patulin in zebrafish.
• To evaluate the toxicological effects of patulin exposure on zebrafish.
• To explore the role of gut microbiota in patulin detoxification.

Main Methods:

• Zebrafish were exposed to a lethal dose of patulin for 24 hours.
• Metabolite profiling was performed using UHPLC-Q-Orbitrap-HRMS.
• Toxicological effects were assessed via histopathology, oxidative stress assays, RT-qPCR, and 16S rRNA sequencing.

Main Results:

• Zebrafish metabolized patulin into ascladiol and hydroascladiol in the intestine, potentially involving Lactobacillus, and formed PAT-GSH adducts in the liver.
• Metabolite levels shifted from non-toxic forms to PAT-GSH adducts over time, correlating with increased inflammation, oxidative stress, and gut dysbiosis.
• Intestinal detoxification capacity was impaired by gut microbiota disruption, leading to increased patulin entering the liver.

Conclusions:

• The intestine serves as an initial defense against patulin, with gut microbiota playing a key role in its detoxification.
• Impaired gut microbiota function under prolonged patulin exposure leads to hepatic toxicity via enterohepatic circulation.
• This study provides novel insights into the in vivo modulation of patulin toxicity and its associated health risks.