The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signaling

Bisphenol S (BPS) has become extensively used in the manufacturing of consumer products. BPS mainly enters the body through food and water, with oral exposure targeting the gastrointestinal tract. However, its safety profile remains contentious and warrants further investigation. In this study, we a...

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Main Authors: Jing Wang, Guolei Niu, Huanzhuo Mai, Xianan Zhang, Jiahao Zhu, Bin Li, Yushuang Gao, Tengkai Huang, Qingtao Meng, Rui Chen
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Environment International
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Online Access:http://www.sciencedirect.com/science/article/pii/S0160412025002284
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author Jing Wang
Guolei Niu
Huanzhuo Mai
Xianan Zhang
Jiahao Zhu
Bin Li
Yushuang Gao
Tengkai Huang
Qingtao Meng
Rui Chen
author_facet Jing Wang
Guolei Niu
Huanzhuo Mai
Xianan Zhang
Jiahao Zhu
Bin Li
Yushuang Gao
Tengkai Huang
Qingtao Meng
Rui Chen
author_sort Jing Wang
collection DOAJ
description Bisphenol S (BPS) has become extensively used in the manufacturing of consumer products. BPS mainly enters the body through food and water, with oral exposure targeting the gastrointestinal tract. However, its safety profile remains contentious and warrants further investigation. In this study, we aimed to assess whether BPS exerts harmful effects on the body in the absence of overt pathological damage. Our results revealed that although BPS did not lead to significant histopathological damage, it induced intestinal barrier dysfunction. Additionally, in vitro investigations utilizing NCM460 cells and human-derived colorectal organoids demonstrated that BPS exposure induced mitochondrial reactive oxygen species (ROS) levels in intestinal endocrine cells (EECs), upregulating the expression of inflammatory mediators TNF-α and CXCL10. Using a DSS-induced colitis mouse model, it was found that BPS exposure exacerbates the progression of intestinal inflammatory diseases. Analysis of single-cell databases demonstrated a significant reduction in the expression of CHGA, a functional protein of enteroendocrine cells (EECs), in patients with inflammatory bowel disease (IBD). The expression of CHGA showed a significant negative correlation with the expression of IL17. Notably, supplementation with 3-Indoleglyoxylic acid effectively mitigates the intestinal damage induced by BPS. These findings highlight the role of mitochondrial oxidative stress and IL-17/CXCL10/TNF-α signaling in BPS-induced intestinal damage and demonstrate the therapeutic potential of 3-Indoleglyoxylic acid in mitigating these effects.
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spelling doaj-art-962ec152a500479d8b51ff08ee9ca34a2025-08-20T02:30:23ZengElsevierEnvironment International0160-41202025-05-0119910947710.1016/j.envint.2025.109477The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signalingJing Wang0Guolei Niu1Huanzhuo Mai2Xianan Zhang3Jiahao Zhu4Bin Li5Yushuang Gao6Tengkai Huang7Qingtao Meng8Rui Chen9School of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, ChinaSchool of Public Health, Capital Medical University, Beijing 100069, China; Corresponding authors at: School of Public Health, Capital Medical University, Beijing 100069, China.School of Public Health, Capital Medical University, Beijing 100069, China; Beijing Key Laboratory of Environment and Aging, Capital Medical University, Beijing 100069, China; Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission, Beijing 100069, China; Laboratory for Environment Health and Allergic Nasal Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing 100069, China; Department of Occupational and Environmental Health, Fourth Military Medical University, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi’an 710032, China; Corresponding authors at: School of Public Health, Capital Medical University, Beijing 100069, China.Bisphenol S (BPS) has become extensively used in the manufacturing of consumer products. BPS mainly enters the body through food and water, with oral exposure targeting the gastrointestinal tract. However, its safety profile remains contentious and warrants further investigation. In this study, we aimed to assess whether BPS exerts harmful effects on the body in the absence of overt pathological damage. Our results revealed that although BPS did not lead to significant histopathological damage, it induced intestinal barrier dysfunction. Additionally, in vitro investigations utilizing NCM460 cells and human-derived colorectal organoids demonstrated that BPS exposure induced mitochondrial reactive oxygen species (ROS) levels in intestinal endocrine cells (EECs), upregulating the expression of inflammatory mediators TNF-α and CXCL10. Using a DSS-induced colitis mouse model, it was found that BPS exposure exacerbates the progression of intestinal inflammatory diseases. Analysis of single-cell databases demonstrated a significant reduction in the expression of CHGA, a functional protein of enteroendocrine cells (EECs), in patients with inflammatory bowel disease (IBD). The expression of CHGA showed a significant negative correlation with the expression of IL17. Notably, supplementation with 3-Indoleglyoxylic acid effectively mitigates the intestinal damage induced by BPS. These findings highlight the role of mitochondrial oxidative stress and IL-17/CXCL10/TNF-α signaling in BPS-induced intestinal damage and demonstrate the therapeutic potential of 3-Indoleglyoxylic acid in mitigating these effects.http://www.sciencedirect.com/science/article/pii/S0160412025002284BPS3-Indoleglyoxylic AcidMitochondrialOrganoids
spellingShingle Jing Wang
Guolei Niu
Huanzhuo Mai
Xianan Zhang
Jiahao Zhu
Bin Li
Yushuang Gao
Tengkai Huang
Qingtao Meng
Rui Chen
The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signaling
Environment International
BPS
3-Indoleglyoxylic Acid
Mitochondrial
Organoids
title The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signaling
title_full The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signaling
title_fullStr The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signaling
title_full_unstemmed The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signaling
title_short The protective role of 3-Indoleglyoxylic acid in Bisphenol S-induced intestinal barrier dysfunction via mitochondrial ROS-Mediated IL-17/CXCL10/TNF-α signaling
title_sort protective role of 3 indoleglyoxylic acid in bisphenol s induced intestinal barrier dysfunction via mitochondrial ros mediated il 17 cxcl10 tnf α signaling
topic BPS
3-Indoleglyoxylic Acid
Mitochondrial
Organoids
url http://www.sciencedirect.com/science/article/pii/S0160412025002284
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