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Dietary iron regulates intestinal goblet cell function and alleviates Salmonella typhimurium invasion in mice

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Abstract

Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens, their roles in anti-infection immunity have frequently been underestimated. To estimate whether adequate dietary iron intake would help defend against pathogenic bacterial infection, mice were fed iron-deficient (2 mg kg−1 feed), iron-sufficient (35 mg kg−1 feed), or iron-enriched diet (350 mg kg−1 feed) for 12 weeks, followed by oral infection with Salmonella typhimurium. Our results revealed that dietary iron intake improved mucus layer function and decelerated the invasion of the pathogenic bacteria, Salmonella typhimurium. Positive correlations between serum iron and the number of goblet cells and mucin2 were found in response to total iron intake in mice. Unabsorbed iron in the intestinal tract affected the gut microbiota composition, and the abundance of Bacteroidales, family Muribaculaceae, was positively correlated with their mucin2 expression. However, the results from antibiotic-treated mice showed that the dietary iron-regulated mucin layer function was not microbial-dependent. Furthermore, in vitro studies revealed that ferric citrate directly induced mucin2 expression and promoted the proliferation of goblet cells in both ileal and colonic organoids. Thus, dietary iron intake improves serum iron levels, regulates goblet cell regeneration and mucin layer function, and plays a positive role in the prevention of pathogenic bacteria.

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Acknowledgements

This work was supported by Outstanding Youth Fund of Hunan Natural Science Foundation (2021JJ20045), the National Natural Science Foundation of China (32130099), the Science and Technology Program of Hunan Province (2020NK2013, 2020GK4095), the Youth Innovation Promotion Association of Chinese Academy of Sciences (2022370), the key R&D Program of Guangxi Province (2021AB20063), the China Agriculture Research System of MOF and MARA, and the National Center of Technology Innovation for Pigs.

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  1. Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China

    Shuan Liu, Zhenlin Dong, Wenjie Tang, Jian Zhou, Liu Guo, Chengyan Gong, Guang Liu, Dan Wan & Yulong Yin

  2. University of Chinese Academy of Sciences, Beijing, 101408, China

    Shuan Liu, Jian Zhou, Liu Guo, Chengyan Gong & Yulong Yin

  3. Animal Breeding and Genetics Key Laboratory of Sichuan Province, Livestock and Poultry Biological Products Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu, 610066, China

    Wenjie Tang

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  1. Shuan Liu
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Liu, S., Dong, Z., Tang, W. et al. Dietary iron regulates intestinal goblet cell function and alleviates Salmonella typhimurium invasion in mice. Sci. China Life Sci. 66, 2006–2019 (2023). https://doi.org/10.1007/s11427-022-2298-1

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