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Innovative 3D microfluidic intestinal organoid model for assessing cadmium bioavailability in food: implications for enhanced exposure risk assessment

Yan Lia,b,1, Wen Suna,b,1, Qiao Wangc, Wan Shic, Yu Chend, Zhiyong Gongc, Xiao Guoc(), Xin Liuc(), Yongning Wuc,e()
Key Laboratory of Animal Biological Products & Genetic Engineering, Ministry of Agriculture and Rural, Sinopharm Animal Health Co., Ltd., Wuhan 430023, China
State Key Laboratory of Novel Vaccines for Emerging Infectious Diseases, China National Biotec Group Co., Ltd., Beijing 100024, China
Key Laboratory for Deep Processing of Major Grain and Oil (The Chinese Ministry of Education), College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China
Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, China
NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing 100021, China

1 These authors contributed equally.

Peer review under responsibility of Beijing Academy of Food Sciences.

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Highlights

• A novel 3D intestinal organoid model was developed to assess Cd bioavailability.

• The new model overcome limitations of conventional planar Transwell model.

• The new model closely recapitulated the physiological intestinal microenvironment.

• The Cd bioavailability in new model was comparable to that of the mouse model.

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Abstract

Given the severe toxicity and widespread presence of cadmium (Cd) in staple foods such as rice, accurate dietary exposure assessments are imperative for public health. In vitro bioavailability is commonly used to adjust dietary exposure levels of risk factors; however, traditional planar Transwell models have limitations, such as cell dedifferentiation and lack of key intestinal components, necessitating a more physiologically relevant in vitro platform. This study introduces an innovative three-dimensional (3D) intestinal organoid model using a microfluidic chip to evaluate Cd bioavailability in food. Caco-2 cells were cultured on the chip to mimic small intestinal villi’s 3D structure, mucus production, and absorption functions. The model’s physiological relevance was thoroughly characterized, demonstrating the formation of a confluent epithelial monolayer with well-developed tight junctions (ZO-1), high microvilli density (F-actin), and significant mucus secretion (Alcian blue staining), closely resembling the physiological intestinal epithelium. Fluorescent particle tracking confirmed its ability to simulate intestinal transport and diffusion. The Cd bioavailability in rice measured by the 3D intestinal organoid model ((9.07 ± 0.21)%) was comparable to the mouse model ((12.82 ± 3.42)%) but significantly lower than the Caco-2 monolayer model ((26.97 ± 1.11)%). This 3D intestinal organoid model provides a novel and reliable strategy for in vitro assessment of heavy metal bioavailability in food, with important implications for food safety and risk assessment.

Keywords

Planar Transwell model3D intestinal organoid modelPhysiological relevanceCd bioavailability

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Food Science and Human Wellness
Volume 14 Issue 5,
May 2025
Article number: 9250364
DOI: 10.26599/FSHW.2024.9250364
Cite this article:
Li Y, Sun W, Wang Q, et al. Innovative 3D microfluidic intestinal organoid model for assessing cadmium bioavailability in food: implications for enhanced exposure risk assessment. Food Science and Human Wellness, 2025, 14(5): 9250364. https://doi.org/10.26599/FSHW.2024.9250364
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