Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice

Bisphenol A (BPA) and diisobutyl (DIBP) phthalate are widely used as typical plasticizers in food packaging. Plasticizers can be released from polymers, migrate into food, and be ingested by humans, leading to various health problems. However, little research has investigated the combined toxicity o...

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Main Authors: Mengge Duan, Yuting Wang, Shiyu Chen, Jiawen Lu, Ruihong Dong, Qiang Yu, Jianhua Xie, Yi Chen
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Foods
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Online Access:https://www.mdpi.com/2304-8158/14/2/214
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author Mengge Duan
Yuting Wang
Shiyu Chen
Jiawen Lu
Ruihong Dong
Qiang Yu
Jianhua Xie
Yi Chen
author_facet Mengge Duan
Yuting Wang
Shiyu Chen
Jiawen Lu
Ruihong Dong
Qiang Yu
Jianhua Xie
Yi Chen
author_sort Mengge Duan
collection DOAJ
description Bisphenol A (BPA) and diisobutyl (DIBP) phthalate are widely used as typical plasticizers in food packaging. Plasticizers can be released from polymers, migrate into food, and be ingested by humans, leading to various health problems. However, little research has investigated the combined toxicity of BPA and DIBP, particularly their intestinal toxicity. Our goal is to analyse the combined toxicity of BPA (50 mg/kg) and DIBP (500 mg/kg) on the intestines of KM mice. Additionally, we tried to find natural products that can inhibit or prevent the combined toxicity of BPA and DIBP. The results indicated that the combination of BPA and DIBP exposure resulted in a reduction of beneficial flora, an increase in D-Lac levels (136 ± 14 μmol/L), an increase in intestinal permeability, activation of the notch pathway, and a decline in intestinal stem cells (ISCs) to goblet cells, compared to single-exposure sources. Nevertheless, <i>Rubus chingii</i> Hu phenolic extract (RHPE) (200, 400 and 600 mg/kg) ameliorated the BPA and DIBP-induced intestinal microbiota disruption and intestinal mucosal barrier impairment by inhibiting the overactivation of the notch pathway. The results of this study highlight the potential risks to human health posed by the combination of BPA and DIBP and may help explain the potential pathways of enterotoxicity caused by combined ingestion.
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publishDate 2025-01-01
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spelling doaj-art-d9bc960c747a44c5b5d6df36f9cb8a692025-01-24T13:32:54ZengMDPI AGFoods2304-81582025-01-0114221410.3390/foods14020214Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in MiceMengge Duan0Yuting Wang1Shiyu Chen2Jiawen Lu3Ruihong Dong4Qiang Yu5Jianhua Xie6Yi Chen7State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaState Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, ChinaBisphenol A (BPA) and diisobutyl (DIBP) phthalate are widely used as typical plasticizers in food packaging. Plasticizers can be released from polymers, migrate into food, and be ingested by humans, leading to various health problems. However, little research has investigated the combined toxicity of BPA and DIBP, particularly their intestinal toxicity. Our goal is to analyse the combined toxicity of BPA (50 mg/kg) and DIBP (500 mg/kg) on the intestines of KM mice. Additionally, we tried to find natural products that can inhibit or prevent the combined toxicity of BPA and DIBP. The results indicated that the combination of BPA and DIBP exposure resulted in a reduction of beneficial flora, an increase in D-Lac levels (136 ± 14 μmol/L), an increase in intestinal permeability, activation of the notch pathway, and a decline in intestinal stem cells (ISCs) to goblet cells, compared to single-exposure sources. Nevertheless, <i>Rubus chingii</i> Hu phenolic extract (RHPE) (200, 400 and 600 mg/kg) ameliorated the BPA and DIBP-induced intestinal microbiota disruption and intestinal mucosal barrier impairment by inhibiting the overactivation of the notch pathway. The results of this study highlight the potential risks to human health posed by the combination of BPA and DIBP and may help explain the potential pathways of enterotoxicity caused by combined ingestion.https://www.mdpi.com/2304-8158/14/2/214BPADIBPintestinal mucosal barriernotch pathwaygut microbiota<i>Rubus chingii</i> Hu phenolic extract
spellingShingle Mengge Duan
Yuting Wang
Shiyu Chen
Jiawen Lu
Ruihong Dong
Qiang Yu
Jianhua Xie
Yi Chen
Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice
Foods
BPA
DIBP
intestinal mucosal barrier
notch pathway
gut microbiota
<i>Rubus chingii</i> Hu phenolic extract
title Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice
title_full Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice
title_fullStr Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice
title_full_unstemmed Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice
title_short Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice
title_sort combined bpa and dibp exposure induced intestinal mucosal barrier impairment through the notch pathway and gut microbiota dysbiosis in mice
topic BPA
DIBP
intestinal mucosal barrier
notch pathway
gut microbiota
<i>Rubus chingii</i> Hu phenolic extract
url https://www.mdpi.com/2304-8158/14/2/214
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