Lactobacillus bulgaricus or Lactobacillus rhamnosus Suppresses NF-κB Signaling Pathway and Protects against AFB1-Induced Hepatitis: A Novel Potential Preventive Strategy for Aflatoxicosis?

Abstract

Aflatoxin B1 (AFB1), a mycotoxin found in food and feed, is immunotoxic to animals and poses significant threat to the food industry and animal production. The primary target of AFB1 is the liver. To overcome aflatoxin toxicity, probiotic-mediated detoxification has been proposed. In the present study, to investigate the protective effects and molecular mechanisms of Lactobacillus bulgaricus or Lactobacillus rhamnosus against liver inflammatory responses to AFB1, mice were administered with AFB1 (300 μg/kg) and/or Lactobacillus intragastrically for 8 weeks. AML12 cells were cultured and treated with AFB1, BAY 11-7082 (an NF-κB inhibitor), and different concentrations of L. bulgaricus or L. rhamnosus. The body weight, liver index, histopathological changes, biochemical indices, cytokines, cytotoxicity, and activation of the NF-κB signaling pathway were measured. AFB1 exposure caused changes in liver histopathology and biochemical functions, altered inflammatory response, and activated the NF-κB pathway. Supplementation of L. bulgaricus or L. rhamnosus significantly prevented AFB1-induced liver injury and alleviated histopathological changes and inflammatory response by decreasing NF-κB p65 expression. The results of in vitro experiments revealed that L. rhamnosus evidently protected against AFB1-induced inflammatory response and decreased NF-κB p65 expression when compared with L. bulgaricus. These findings indicated that AFB1 exposure can cause inflammatory response by inducing hepatic injury, and supplementation of L. bulgaricus or L. rhamnosus can produce significant protective effect against AFB1-induced liver damage and inflammatory response by regulating the activation of the NF-κB signaling pathway.

Contamination of Aflatoxins Induces Severe Hepatotoxicity Through Multiple Mechanisms

“…Unsurprisingly, the upregulation of TLR-2/4 was verified at different doses of AFs ( Muhammad et al, 2018b ; Huang et al, 2019 ; Wang et al, 2019 ). Several papers found that the mRNA and protein expression of NF-κB was upregulated in hepatocytes after exposure to AFs ( Ma et al, 2015 ; Oskoueian et al, 2015 ; Muhammad et al, 2018b ; Chen et al, 2019a ; Huang et al, 2019 ; Zhang et al, 2019 ). NF-κB binds to an inhibitory protein called IκB in the resting state and remains sequestered in the cytoplasm.…”

“…Although upstream signaling events differ between individual receptors, the IκB-kinase (IKK) complex is eventually activated, which subsequently inactivates the inhibitory chaperone IκBα of NF-κB ( Afonina et al, 2017 ). Several research papers demonstrated that the expression level of IκB was inhibited in AFs group ( Chen et al, 2019a ; Huang et al, 2019 ). The mRNA level of IKK increased, but it was not significant ( Mughal et al, 2017 ).…”

Effects of Compound Probiotics and Aflatoxin-Degradation Enzyme on Alleviating aflatoxin-induced cytotoxicity in chicken embryo primary intestinal epithelium, liver and kidney cells

“…The reason why high ADE concentrations could in uence cell viability may be due to the high levels of enzymes existing in ADE to damage cells, so low ADE concentration is selected in this study. It was reported that supplementation of L. bulgaricus or L. rhamnosus could produce signi cant protective effect against AFB 1 -induced liver damage and in ammatory response (Chen et al 2019). Moreover, the addition of compound probiotics and mycotoxin-degradation enzyme could prevent broilers from damages induced by AFB 1 (Zuo et al 2013).…”

Aflatoxin Detoxification Using Microorganisms and Enzymes

“…Fan et al researched the ability of Bacillus subtilis ANSB060 to detoxify AFs. Their results showed that B. subtilis improved the growth performance and meat quality of broilers [ 138 ]. The levels of AF residues in the livers of broilers consuming naturally moldy peanut meal were also decreased [ 134 ].…”

“…The levels of AF residues in the livers of broilers consuming naturally moldy peanut meal were also decreased [ 134 ]. Chen et al found that oral Lactobacillus bulgaricus or Lactobacillus rhamnosus ingestion can significantly prevent liver injury induced by AFB1, and reduce histopathological changes and inflammation by elevating the expression of NF-κB p65 [ 138 ]. Feeding with Lactobacillus plantarum 299v can decrease the contents of serum lactate dehydrogenase and alanine aminotransferase in the liver and increase the body weight of broilers by about 20%-55%, bringing economic benefits [ 139 ].…”