Lacticaseibacillus paracasei RM081 ameliorating aflatoxin B1 toxicity in vitro and in vivo

報告時間：2024-06-21
報告地點：Room 407
指導老師：Yen-Po, Chen
學生：Solomon Abrehame
摘要

Aflatoxin B1 (AFB1), a potent carcinogen produced by Aspergillus fungi, poses a significant threat to human and animal health. This study investigates the ability of a novel probiotic strain of Lacticaseibacillus paracasei, RM081, isolated from milk for its tremendous production of the anti-inflammatory metabolite 5-methoxytryptophan (5-MTP), to counteract AFB1 intoxication. Our specific objectives were to demonstrate the binding ability of RM081 to AFB1 using in silico and in vitro assays, evaluate the efficacy of RM081 components (live cells, cell-free extracts/sonicated cell proteins, fermented supernatants, and heat-killed cells) in reducing AFB1-induced intestinal and hepatic toxicity in cell models and mice, and elucidate the mechanisms underlying RM081's ameliorative effects. In silico analysis revealed promising binding between RM081 proteins and AFB1. Molecular docking demonstrated binding sites for AFB1 on all six selected proteins of L. paracasei. In vitro studies confirmed this binding capacity, with all RM081 components exhibiting significant AFB1 adsorption (up to 92%). Furthermore, these components significantly alleviated AFB1-induced toxicity in Caco2 intestinal epithelial cells. In vivo experiments, using a mouse model demonstrated that RM081 administration improved general health markers (body weight, organ weight ratio) and vital organ function (liver function tests, histology) in AFB1 intoxication. Additionally, RM081 reduced urinary AFM1 levels (an AFB1 metabolite), suggesting abrogation of AFB1 metabolism in the body. Moreover, RM081 reduced inflammatory cytokines levels from tissues and serum samples as well as the cell models. Upon searching for the possible mechanisms, RM081 treatment downregulated the inflammatory enzyme COX-2, which is upregulated by AFB1 in both cell and mouse models, indicating anti-inflammatory properties. These findings highlight the potential of RM081 as a powerful tool to combat AFB1 intoxication. Future applications include its use as a feed additive to safeguard the food chain from AFB1 contamination.
 
Keywords: Aflatoxin B1, Lacticaseibacillus paracasei RM081, Adsorption, In silico, In vitro, In vivo, Probiotics, Postbiotics, RM081
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