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Trace metal elements: a bridge between host and intestinal microorganisms

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Abstract

Trace metal elements, such as iron, copper, manganese, and zinc, are essential nutrients for biological processes. Although their intake demand is low, they play a crucial role in cell homeostasis as the cofactors of various enzymes. Symbiotic intestinal microorganisms compete with their host for the use of trace metal elements. Moreover, the metabolic processes of trace metal elements in the host and microorganisms affect the organism’s health. Supplementation or the lack of trace metal elements in the host can change the intestinal microbial community structure and function. Functional changes in symbiotic microorganisms can affect the host’s metabolism of trace metal elements. In this review, we discuss the absorption and transport processes of trace metal elements in the host and symbiotic microorganisms and the effects of dynamic changes in the levels of trace metal elements on the intestinal microbial community structure. We also highlight the participation of trace metal elements as enzyme cofactors in the host immune process. Our findings indicate that the host uses metal nutrition immunity or metal poisoning to resist pathogens and improve immunity.

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References

  • Abrantes, M.C., Lopes Mde, F., and Kok, J. (2011). Impact of manganese, copper and zinc ions on the transcriptome of the nosocomial pathogen enterococcus faecalis v583. PLoS ONE 6, e26519.

    Article  CAS  PubMed  Google Scholar 

  • Achard, M.E.S., Stafford, S.L., Bokil, N.J., Chartres, J., Bernhardt, P.V., Schembri, M.A., Sweet, M.J., and McEwan, A.G. (2012). Copper redistribution in murine macrophages in response to Salmonella infection. Biochem J 444, 51–57.

    Article  CAS  PubMed  Google Scholar 

  • Agoro, R., Benmerzoug, S., Rose, S., Bouyer, M., Gozzelino, R., Garcia, I., Ryffel, B., Quesniaux, V.F.J., and Mura, C. (2017). An iron-rich diet decreases the mycobacterial burden and correlates with hepcidin upregulation, lower levels of proinflammatory mediators, and increased T-cell recruitment in a model of Mycobacterium bovis bacille calmette-guerin infection. J Infect Dis 216, 907–918.

    Article  CAS  PubMed  Google Scholar 

  • Aisen, P. (2004). Transferrin receptor 1. Int J Biochem Cell Biol 36, 2137–2143.

    Article  CAS  PubMed  Google Scholar 

  • Alteri, C.J., Hagan, E.C., Sivick, K.E., Smith, S.N., and Mobley, H.L. (2009). Mucosal immunization with iron receptor antigens protects against urinary tract infection. PLoS Pathog 5, e1000586.

    Article  PubMed  PubMed Central  Google Scholar 

  • Amachawadi, R.G., Scott, H.M., Nitikanchana, S., Vinasco, J., Tokach, M. D., Dritz, S.S., Nelssen, J.L., Goodband, R.D., and Nagaraja, T.G. (2015). Nasal carriage of mecA-positive methicillin-resistant Staphylococcus aureus in pigs exhibits dose-response to zinc supplementation. Foodborne Pathog Dis 12, 159–163.

    Article  CAS  PubMed  Google Scholar 

  • Anagianni, S., and Tuschl, K. (2019). Genetic disorders of manganese metabolism. Curr Neurol Neurosci Rep 19, 33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andreini, C., Banci, L., Bertini, I., and Rosato, A. (2006). Counting the zinc-proteins encoded in the human genome. J Proteome Res 5, 196–201.

    Article  CAS  PubMed  Google Scholar 

  • Andreini, C., Bertini, I., Cavallaro, G., Holliday, G.L., and Thornton, J.M. (2008). Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem 13, 1205–1218.

    Article  CAS  PubMed  Google Scholar 

  • Andrews, S.C., Robinson, A.K., and Rodríguez-Quiñones, F. (2003). Bacterial iron homeostasis. FEMS Microbiol Rev 27, 215–237.

    Article  CAS  PubMed  Google Scholar 

  • Arnold, J.W., Roach, J., and Azcarate-Peril, M.A. (2016). Emerging technologies for gut microbiome research. Trends Microbiol 24, 887–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aschner, J.L., and Aschner, M. (2005). Nutritional aspects of manganese homeostasis. Mol Aspects Med 26, 353–362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aschner, M., and Erikson, K. (2017). Manganese. Adv Nutr 8, 520–521.

    Article  PubMed  PubMed Central  Google Scholar 

  • Azcárate, I.G., Sánchez-Jaut, S., Marín-García, P., Linares, M., Pérez-Benavente, S., García-Sánchez, M., Uceda, J., Kamali, A.N., Morán-Jiménez, M.J., Puyet, A., et al. (2017). Iron supplementation in mouse expands cellular innate defences in spleen and defers lethal malaria infection. Biochim Biophys Acta Mol Basis Dis 1863, 3049–3059.

    Article  PubMed  Google Scholar 

  • Barth, V.C., Chauhan, U., Zeng, J., Su, X., Zheng, H., Husson, R.N., and Woychik, N.A. (2021). Mycobacterium tuberculosis VapC4 toxin engages small ORFs to initiate an integrated oxidative and copper stress response. Proc Natl Acad Sci USA 118, e2022136118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker, K.W., and Skaar, E.P. (2014). Metal limitation and toxicity at the interface between host and pathogen. FEMS Microbiol Rev 38, 1235–1249.

    Article  CAS  PubMed  Google Scholar 

  • Bednorz, C., Oelgeschläger, K., Kinnemann, B., Hartmann, S., Neumann, K., Pieper, R., Bethe, A., Semmler, T., Tedin, K., Schierack, P., et al. (2013). The broader context of antibiotic resistance: zinc feed supplementation of piglets increases the proportion of multi-resistant Escherichia coli in vivo. Int J Med Microbiol 303, 396–403.

    Article  CAS  PubMed  Google Scholar 

  • Ben-Eghan, C., Sun, R., Hleap, J.S., Diaz-Papkovich, A., Munter, H.M., Grant, A.V., Dupras, C., and Gravel, S. (2020). Don’t ignore genetic data from minority populations. Nature 585, 184–186.

    Article  CAS  PubMed  Google Scholar 

  • Bergamaschi, G., Di Sabatino, A., Pasini, A., Ubezio, C., Costanzo, F., Grataroli, D., Masotti, M., Alvisi, C., and Corazza, G.R. (2017). Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin. Clin Nutr 36, 1427–1433.

    Article  CAS  PubMed  Google Scholar 

  • Biesalski, H.K. (2016). Nutrition meets the microbiome: micronutrients and the microbiota. Ann N Y Acad Sci 1372, 53–64.

    Article  PubMed  Google Scholar 

  • Bonaccorsi-Riani, E., Danger, R., Lozano, J.J., Martinez-Picola, M., Kodela, E., Mas-Malavila, R., Bruguera, M., Collins, H.L., Hider, R.C., Martinez-Llordella, M., et al. (2015). Iron deficiency impairs intrahepatic lymphocyte mediated immune response. PLoS ONE 10, e0136106.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bowman, A.B., Kwakye, G.F., Herrero Hernández, E., and Aschner, M. (2011). Role of manganese in neurodegenerative diseases. J Trace Elem Med Biol 25, 191–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cairo, G., Recalcati, S., Mantovani, A., and Locati, M. (2011). Iron trafficking and metabolism in macrophages: contribution to the polarized phenotype. Trends Immunol 32, 241–247.

    Article  CAS  PubMed  Google Scholar 

  • Canonne-Hergaux, F., Gruenheid, S., Ponka, P., and Gros, P. (1999). Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93, 4406–4417.

    Article  CAS  PubMed  Google Scholar 

  • Carpenter, C.B., Woodworth, J.C., Derouchey, J.M., Tokach, M.D., Goodband, R.D., Dritz, S.S., Wu, F., and Rambo, Z.J. (2019). Effects of increasing copper from either copper sulfate or combinations of copper sulfate and a copper-amino acid complex on finishing pig growth performance and carcass characteristics. Transl Anim Sci 3, 1263–1269.

    Article  PubMed  PubMed Central  Google Scholar 

  • Carvalho, F.A., Koren, O., Goodrich, J.K., Johansson, M.E.V., Nalbantoglu, I., Aitken, J.D., Su, Y., Chassaing, B., Walters, W.A., González, A., et al. (2012). Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 12, 139–152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cassat, J.E., and Skaar, E.P. (2013). Iron in infection and immunity. Cell Host Microbe 13, 509–519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaturvedi, K.S., Hung, C.S., Crowley, J.R., Stapleton, A.E., and Henderson, J.P. (2012). The siderophore yersiniabactin binds copper to protect pathogens during infection. Nat Chem Biol 8, 731–736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, L., Lin, Y.L., Peng, G., and Li, F. (2012). Structural basis for multifunctional roles of mammalian aminopeptidase N. Proc Natl Acad Sci USA 109, 17966–17971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, P., Bornhorst, J., and Aschner, M. (2018). Manganese metabolism in humans. Front Biosci 23, 1655–1679.

    Article  CAS  Google Scholar 

  • Chi, L., Gao, B., Bian, X., Tu, P., Ru, H., and Lu, K. (2017). Manganese-induced sex-specific gut microbiome perturbations in C57BL/6 mice. Toxicol Appl Pharmacol 331, 142–153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chi, Y., Chen, X., Li, Y., Wang, C., Zhang, T., Ayoub, A., Warren, A., Song, W., and Wang, Y. (2021). New contributions to the phylogeny of the ciliate class Heterotrichea (Protista, Ciliophora): analyses at family-genus level and new evolutionary hypotheses. Sci China Life Sci 64, 606–620.

    Article  CAS  PubMed  Google Scholar 

  • Cho, J.M., and Yang, H.R. (2018). Hair mineral and trace element contents as reliable markers of nutritional status compared to serum levels of these elements in children newly diagnosed with inflammatory bowel disease. Biol Trace Elem Res 185, 20–29.

    Article  CAS  PubMed  Google Scholar 

  • Choi, E.K., Aring, L., Das, N.K., Solanki, S., Inohara, N., Iwase, S., Samuelson, L.C., Shah, Y.M., and Seo, Y.A. (2020). Impact of dietary manganese on experimental colitis in mice. FASEB J 34, 2929–2943.

    Article  CAS  PubMed  Google Scholar 

  • Chu, B.C., Garcia-Herrero, A., Johanson, T.H., Krewulak, K.D., Lau, C.K., Peacock, R.S., Slavinskaya, Z., and Vogel, H.J. (2010). Siderophore uptake in bacteria and the battle for iron with the host; a bird’s eye view. Biometals 23, 601–611.

    Article  CAS  PubMed  Google Scholar 

  • Cohen, M.S., Britigan, B.E., Hassett, D.J., and Rosen, G.M. (1988). Do humans neutrophils form hydroxyl radical? Evaluation of an unresolved controversy. Free Radic Biol Med 5, 81–88.

    Article  CAS  PubMed  Google Scholar 

  • Cragg, R.A., Christie, G.R., Phillips, S.R., Russi, R.M., Küry, S., Mathers, J.C., Taylor, P.M., and Ford, D. (2002). A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane. J Biol Chem 277, 22789–22797.

    Article  CAS  PubMed  Google Scholar 

  • Cragg, R.A., Phillips, S.R., Piper, J.M., Varma, J.S., Campbell, F.C., Mathers, J.C., and Ford, D. (2005). Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation. Gut 54, 469–478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crofts, A.A., Poly, F.M., Ewing, C.P., Kuroiwa, J.M., Rimmer, J.E., Harro, C., Sack, D., Talaat, K.R., Porter, C.K., Gutierrez, R.L., et al. (2018). Campylobacter jejuni transcriptional and genetic adaptation during human infection. Nat Microbiol 3, 494–502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cronin, S.J.F., Woolf, C.J., Weiss, G., and Penninger, J.M. (2019). The role of iron regulation in immunometabolism and immune-related disease. Front Mol Biosci 6, 116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cunrath, O., Geoffroy, V.A., and Schalk, I.J. (2016). Metallome of Pseudomonas aeruginosa a role for siderophores. Environ Microbiol 18, 3258–3267.

    Article  CAS  PubMed  Google Scholar 

  • Dalecki, A.G., Crawford, C.L., and Wolschendorf, F. (2017). Copper and antibiotics: discovery, modes of action, and opportunities for medicinal applications. Adv Microb Physiol 70, 193–260.

    Article  CAS  PubMed  Google Scholar 

  • Damo, S., Chazin, W.J., Skaar, E.P., and Kehl-Fie, T.E. (2012). Inhibition of bacterial superoxide defense: a new front in the struggle between host and pathogen. Virulence 3, 325–328.

    Article  PubMed  PubMed Central  Google Scholar 

  • Damo, S.M., Kehl-Fie, T.E., Sugitani, N., Holt, M.E., Rathi, S., Murphy, W. J., Zhang, Y., Betz, C., Hench, L., Fritz, G., et al. (2013). Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens. Proc Natl Acad Sci USA 110, 3841–3846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Das, A., Ash, D., Fouda, A.Y., Sudhahar, V., Kim, Y.M., Hou, Y., Hudson, F.Z., Stansfield, B.K., Caldwell, R.B., McMenamin, M., et al. (2022). Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis. Nat Cell Biol 24, 35–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Das, N.K., Schwartz, A.J., Barthel, G., Inohara, N., Liu, Q., Sankar, A., Hill, D.R., Ma, X., Lamberg, O., Schnizlein, M.K., et al. (2020). Microbial metabolite signaling is required for systemic iron homeostasis. Cell Metab 31, 115–130.e6.

    Article  CAS  PubMed  Google Scholar 

  • David, L.A., Maurice, C.F., Carmody, R.N., Gootenberg, D.B., Button, J.E., Wolfe, B.E., Ling, A.V., Devlin, A.S., Varma, Y., Fischbach, M.A., et al. (2014). Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563.

    Article  CAS  PubMed  Google Scholar 

  • Davison, J. (1999). Genetic exchange between bacteria in the environment. Plasmid 42, 73–91.

    Article  CAS  PubMed  Google Scholar 

  • Dębski, B. (2016). Supplementation of pigs diet with zinc and copper as alternative to conventional antimicrobials. Pol J Vet Sci 19, 917–924.

    Article  PubMed  Google Scholar 

  • Deriu, E., Liu, J.Z., Pezeshki, M., Edwards, R.A., Ochoa, R.J., Contreras, H., Libby, S.J., Fang, F.C., and Raffatellu, M. (2013). Probiotic bacteria reduce Salmonella typhimurium intestinal colonization by competing for iron. Cell Host Microbe 14, 26–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deschemin, J.C., Noordine, M.L., Remot, A., Willemetz, A., Afif, C., Canonne-Hergaux, F., Langella, P., Karim, Z., Vaulont, S., Thomas, M., et al. (2016). The microbiota shifts the iron sensing of intestinal cells. FASEB J 30, 252–261.

    Article  CAS  PubMed  Google Scholar 

  • Devi, S.R.B., Dhivya M, A., and Sulochana, K.N. (2016). Copper transporters and chaperones: Their function on angiogenesis and cellular signalling. J Biosci 41, 487–496.

    Article  CAS  Google Scholar 

  • Di Renzo, L., Gualtieri, P., Pivari, F., Soldati, L., Attinà, A., Leggeri, C., Cinelli, G., Tarsitano, M.G., Caparello, G., Carrano, E., et al. (2020). COVID-19: is there a role for immunonutrition in obese patient? J Transl Med 18, 415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diao, H., Jiao, A.R., Yu, B., Mao, X.B., and Chen, D.W. (2019). Gastric infusion of short-chain fatty acids can improve intestinal barrier function in weaned piglets. Genes Nutr 14, 4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diaz-Ochoa, V.E., Lam, D., Lee, C.S., Klaus, S., Behnsen, J., Liu, J.Z., Chim, N., Nuccio, S.P., Rathi, S.G., Mastroianni, J.R., et al. (2016). Salmonella mitigates oxidative stress and thrives in the inflamed gut by evading calprotectin-mediated manganese sequestration. Cell Host Microbe 19, 814–825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding, C., Festa, R.A., Chen, Y.L., Espart, A., Palacios, Ò., Espín, J., Capdevila, M., Atrian, S., Heitman, J., and Thiele, D.J. (2013). Cryptococcus neoformans copper detoxification machinery is critical for fungal virulence. Cell Host Microbe 13, 265–276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding, C., Festa, R.A., Sun, T.S., and Wang, Z.Y. (2014). Iron and copper as virulence modulators in human fungal pathogens. Mol Microbiol 93, 10–23.

    Article  CAS  PubMed  Google Scholar 

  • Djoko, K.Y., Ong, C.Y., Walker, M.J., and McEwan, A.G. (2015). The role of copper and zinc toxicity in innate immune defense against bacterial pathogens. J Biol Chem 290, 18954–18961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doguer, C., Ha, J.H., and Collins, J.F. (2018). Intersection of iron and copper metabolism in the mammalian intestine and liver. Compr Physiol 8, 1433–1461.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dostal, A., Chassard, C., Hilty, F.M., Zimmermann, M.B., Jaeggi, T., Rossi, S., and Lacroix, C. (2012). Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J Nutr 142, 271–277.

    Article  CAS  PubMed  Google Scholar 

  • Dostal, A., Fehlbaum, S., Chassard, C., Zimmermann, M.B., and Lacroix, C. (2013). Low iron availability in continuous in vitro colonic fermentations induces strong dysbiosis of the child gut microbial consortium and a decrease in main metabolites. FEMS Microbiol Ecol 83, 161–175.

    Article  CAS  PubMed  Google Scholar 

  • Dostal, A., Lacroix, C., Bircher, L., Pham, V.T., Follador, R., Zimmermann, M.B., and Chassard, C. (2015). Iron modulates butyrate production by a child gut microbiota invitro. mBio 6, e01453–01415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan, H., Yu, L., Tian, F., Zhai, Q., Fan, L., and Chen, W. (2020). Gut microbiota: A target for heavy metal toxicity and a probiotic protective strategy. Sci Total Environ 742, 140429.

    Article  CAS  PubMed  Google Scholar 

  • Duan, Y., Zheng, C., Zheng, J., Ma, L., Ma, X., Zhong, Y., Zhao, X., Li, F., Guo, Q., and Yin, Y. (2023). Profiles of muscular amino acids, fatty acids, and metabolites in Shaziling pigs of different ages and relation to meat quality. Sci China Life Sci 66, 1323–1339.

    Article  CAS  PubMed  Google Scholar 

  • Dufner-Beattie, J., Kuo, Y.M., Gitschier, J., and Andrews, G.K. (2004). The adaptive response to dietary zinc in mice involves the differential cellular localization and zinc regulation of the zinc transporters ZIP4 and ZIP5. J Biol Chem 279, 49082–49090.

    Article  CAS  PubMed  Google Scholar 

  • Ellermann, M., Gharaibeh, R.Z., Maharshak, N., Peréz-Chanona, E., Jobin, C., Carroll, I.M., Arthur, J.C., Plevy, S.E., Fodor, A.A., Brouwer, C.R., et al. (2020). Dietary iron variably modulates assembly of the intestinal microbiota in colitis-resistant and colitis-susceptible mice. Gut Microbes 11, 32–50.

    Article  CAS  PubMed  Google Scholar 

  • Festa, R.A., Jones, M.B., Butler-Wu, S., Sinsimer, D., Gerads, R., Bishai, W.R., Peterson, S.N., and Darwin, K.H. (2011). A novel copper-responsive regulon in Mycobacterium tuberculosis. Mol Microbiol 79, 133–148.

    Article  CAS  PubMed  Google Scholar 

  • Fillat, M.F. (2014). The FUR (ferric uptake regulator) superfamily: diversity and versatility of key transcriptional regulators. Arch Biochem Biophys 546, 41–52.

    Article  CAS  PubMed  Google Scholar 

  • Fraga, C.G. (2005). Relevance, essentiality and toxicity of trace elements in human health. Mol Aspects Med 26, 235–244.

    Article  CAS  PubMed  Google Scholar 

  • Franke, S., Grass, G., Rensing, C., and Nies, D.H. (2003). Molecular analysis of the copper-transporting efflux system CusCFBA of Escherichia coli. J Bacteriol 185, 3804–3812.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fu, Y., Chang, F.M.J., and Giedroc, D.P. (2014). Copper transport and trafficking at the host-bacterial pathogen interface. Acc Chem Res 47, 3605–3613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao, J., Yang, Z., Zhao, C., Tang, X., Jiang, Q., and Yin, Y. (2023). A comprehensive review on natural phenolic compounds as alternatives to in-feed antibiotics. Sci China Life Sci 66, 1518–1534.

    Article  PubMed  Google Scholar 

  • Garcia, Y.M., Barwinska-Sendra, A., Tarrant, E., Skaar, E.P., Waldron, K.J., and Kehl-Fie, T.E. (2017). A superoxide dismutase capable of functioning with iron or manganese promotes the resistance of Staphylococcus aureus to calprotectin and nutritional immunity. PLoS Pathog 13, e1006125.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gaulke, C.A., Rolshoven, J., Wong, C.P., Hudson, L.G., Ho, E., and Sharpton, T.J. (2018). Marginal zinc deficiency and environmentally relevant concentrations of arsenic elicit combined effects on the gut microbiome. mSphere 3, e00521–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geiser, J., Venken, K.J., De Lisle, R.C., and Andrews, G.K. (2012). A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. PLoS Genet 8, e1002766.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ghaisas, S., Harischandra, D.S., Palanisamy, B., Proctor, A., Jin, H., Dutta, S., Sarkar, S., Langley, M., Zenitsky, G., Anantharam, V., et al. (2021). Chronic manganese exposure and the enteric nervous system: an in vitro and mouse in vivo study. Environ Health Perspect 129, 87005.

    Article  CAS  PubMed  Google Scholar 

  • Giachino, A., and Waldron, K.J. (2020). Copper tolerance in bacteria requires the activation of multiple accessory pathways. Mol Microbiol 114, 377–390.

    Article  CAS  PubMed  Google Scholar 

  • Grass, G., Thakali, K., Klebba, P.E., Thieme, D., Muller, A., Wildner, G..F., and Rensing, C. (2004). Linkage between catecholate siderophores and the multicopper oxidase CueO in Escherichia coli. J Bacteriol 186, 5826–5833.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guilhen, C., Taha, M.K., and Veyrier, F.J. (2013). Role of transition metal exporters in virulence: the example of Neisseria meningitidis. Front Cell Infect Microbiol 3, 102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gulec, S., Anderson, G.J., and Collins, J.F. (2014). Mechanistic and regulatory aspects of intestinal iron absorption. Am J Physiol Gastrointest Liver Physiol 307, G397–G409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gunter, T.E., Gerstner, B., Gunter, K.K., Malecki, J., Gelein, R., Valentine, W.M., Aschner, M., and Yule, D.I. (2013). Manganese transport via the transferrin mechanism. Neurotoxicology 34, 118–127.

    Article  CAS  PubMed  Google Scholar 

  • Hamza, I., Prohaska, J., and Gitlin, J.D. (2003). Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. Proc Natl Acad Sci USA 100, 1215–1220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harischandra, D.S., Ghaisas, S., Zenitsky, G., Jin, H., Kanthasamy, A., Anantharam, V., and Kanthasamy, A.G. (2019). Manganese-induced neurotoxicity: new insights into the triad of protein misfolding, mitochondrial impairment, and neuroinflammation. Front Neurosci 13, 654.

    Article  PubMed  PubMed Central  Google Scholar 

  • Haschka, D., Hoffmann, A., and Weiss, G. (2021). Iron in immune cell function and host defense. Semin Cell Dev Biol 115, 27–36.

    Article  CAS  PubMed  Google Scholar 

  • Haschka, D., Nairz, M., Demetz, E., Wienerroither, S., Decker, T., and Weiss, G. (2015). Contrasting regulation of macrophage iron homeostasis in response to infection with Listeria monocytogenes depending on localization of bacteria. Metallomics 7, 1036–1045.

    Article  CAS  PubMed  Google Scholar 

  • Hohle, T.H., Franck, W.L., Stacey, G., and O’Brian, M.R. (2011). Bacterial outer membrane channel for divalent metal ion acquisition. Proc Natl Acad Sci USA 108, 15390–15395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Honda, K., and Littman, D.R. (2016). The microbiota in adaptive immune homeostasis and disease. Nature 535, 75–84.

    Article  CAS  PubMed  Google Scholar 

  • Horn, N., and Wittung-Stafshede, P. (2021). ATP7A-regulated enzyme metalation and trafficking in the Menkes disease puzzle. Biomedicines 9, 391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imperi, F., Tiburzi, F., and Visca, P. (2009). Molecular basis of pyoverdine siderophore recycling in Pseudomonas aeruginosa. Proc Natl Acad Sci USA 106, 20440–20445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaeggi, T., Kortman, G.A.M., Moretti, D., Chassard, C., Holding, P., Dostal, A., Boekhorst, J., Timmerman, H.M., Swinkels, D.W., Tjalsma, H., et al. (2015). Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 64, 731–742.

    Article  CAS  PubMed  Google Scholar 

  • Jin, Q., Yang, X., Gou, S., Liu, X., Zhuang, Z., Liang, Y., Shi, H., Huang, J., Wu, H., Zhao, Y., et al. (2022). Double knock-in pig models with elements of binary Tet-On and phiC31 integrase systems for controllable and switchable gene expression. Sci China Life Sci 65, 2269–2286.

    Article  CAS  PubMed  Google Scholar 

  • Jones, C.M., Wells, R.M., Madduri, A.V.R., Renfrow, M.B., Ratledge, C., Moody, D.B., and Niederweis, M. (2014). Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling. Proc Natl Acad Sci USA 111, 1945–1950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones, D.G., and Suttle, N.F. (1981). Some effects of copper deficiency on leucocyte function in sheep and cattle. Res Vet Sci 31, 151–156.

    Article  CAS  PubMed  Google Scholar 

  • Juttukonda, L.J., Berends, E.T.M., Zackular, J.P., Moore, J.L., Stier, M.T., Zhang, Y., Schmitz, J.E., Beavers, W.N., Wijers, C.D., Gilston, B.A., et al. (2017). Dietary manganese promotes staphylococcal infection of the heart. Cell Host Microbe 22, 531–542.e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katumba, G.L., Tran, H., and Henderson, J.P. (2022). The Yersinia high-pathogenicity island encodes a siderophore-dependent copper response system in uropathogenic Escherichiacoli. mBio 13, e0239121.

    Article  PubMed  Google Scholar 

  • Kociova, S., Dolezelikova, K., Horky, P., Skalickova, S., Baholet, D., Bozdechova, L., Vaclavkova, E., Belkova, J., Nevrkla, P., Skladanka, J., et al. (2020). Zinc phosphate-based nanoparticles as alternatives to zinc oxide in diet of weaned piglets. J Anim Sci Biotechnol 11, 59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krebs, N.F., Sherlock, L.G., Westcott, J., Culbertson, D., Hambidge, K.M., Feazel, L.M., Robertson, C.E., and Frank, D.N. (2013). Effects of different complementary feeding regimens on iron status and enteric microbiota in breastfed infants. J Pediatr 163, 416–423.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krewulak, K.D., and Vogel, H.J. (2008). Structural biology of bacterial iron uptake. Biochim Biophys Acta 1778, 1781–1804.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, P., Sannigrahi, S., and Tzeng, Y.L. (2012). The Neisseria meningitidis znud zinc receptor contributes to interactions with epithelial cells and supports heme utilization when expressed in Escherichia coli. Infect Immun 80, 657–667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lassi, Z.S., Moin, A., and Bhutta, Z.A. (2016). Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database Syst Rev 12, Cd005978.

    PubMed  Google Scholar 

  • Lazarchick, J. (2012). Update on anemia and neutropenia in copper deficiency. Curr Opin Hematol 19, 58–60.

    Article  CAS  PubMed  Google Scholar 

  • Lee, T., Clavel, T., Smirnov, K., Schmidt, A., Lagkouvardos, I., Walker, A., Lucio, M., Michalke, B., Schmitt-Kopplin, P., Fedorak, R., et al. (2017). Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 66, 863–871.

    Article  CAS  PubMed  Google Scholar 

  • Li, L.Y., Chen, M.Y., Liu, W.Y., Tai, P.Z., Liu, X., and Liu, J. (2022a). Zebrafish cox17 modulates primitive erythropoiesis via regulation of mitochondrial metabolism to facilitate hypoxia tolerance. FASEB J 36, e22596.

    Article  CAS  PubMed  Google Scholar 

  • Li, X.Y., Mei, J., Ge, C.T., Liu, X.L., and Gui, J.F. (2022b). Sex determination mechanisms and sex control approaches in aquaculture animals. Sci China Life Sci 65, 1091–1122.

    Article  PubMed  Google Scholar 

  • Lin, H., Fischbach, M.A., Liu, D.R., and Walsh, C.T. (2005). In vitro characterization of salmochelin and enterobactin trilactone hydrolases IroD, IroE, and Fes. J Am Chem Soc 127, 11075–11084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, Y., Zhang, S., Deng, H., Chen, A., and Chai, L. (2022). Lead and copper led to the dysregulation of bile acid homeostasis by impairing intestinal absorption in Bufo gargarizans larvae: an integrated metabolomics and transcriptomics approach. Sci Total Environ 855, 159031.

    Article  PubMed  Google Scholar 

  • Lopez, C.A., and Skaar, E.P. (2018). The impact of dietary transition metals on host-bacterial interactions. Cell Host Microbe 23, 737–748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv, M., Chen, M., Zhang, R., Zhang, W., Wang, C., Zhang, Y., Wei, X., Guan, Y., Liu, J., Feng, K., et al. (2020). Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy. Cell Res 30, 966–979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Macedo, M.F., De Sousa, M., Ned, R.M., Mascarenhas, C., Andrews, N.C., and Correia-Neves, M. (2004). Transferrin is required for early T-cell differentiation. Immunology 112, 543–549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Macomber, L., Rensing, C., and Imlay, J.A. (2007). Intracellular copper does not catalyze the formation of oxidative DNA damage in Escherichia coli. J Bacteriol 189, 1616–1626.

    Article  CAS  PubMed  Google Scholar 

  • Maresso, A.W., Chapa, T.J., and Schneewind, O. (2006). Surface protein IsdC and Sortase B are required for heme-iron scavenging of Bacillus anthracis. J Bacteriol 188, 8145–8152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maresso, A.W., Garufi, G., and Schneewind, O. (2008). Bacillusanthracis secretes proteins that mediate heme acquisition from hemoglobin. PLoS Pathog 4, e1000132.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maret, W. (2010). Metalloproteomics, metalloproteomes, and the annotation of metalloproteins. Metallomics 2, 117–125.

    Article  CAS  PubMed  Google Scholar 

  • Maryon, E.B., Molloy, S.A., Ivy, K., Yu, H., and Kaplan, J.H. (2013). Rate and regulation of copper transport by human copper transporter 1 (hCTR1). J Biol Chem 288, 18035–18046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maughan, R.J. (1999). Role of micronutrients in sport and physical activity. Br Med Bull 55, 683–690.

    Article  CAS  PubMed  Google Scholar 

  • Mayneris-Perxachs, J., Cardellini, M., Hoyles, L., Latorre, J., Davato, F., Moreno-Navarrete, J.M., Arnoriaga-Rodríguez, M., Serino, M., Abbott, J., Barton, R.H., et al. (2021). Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome. Microbiome 9, 104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayneris-Perxachs, J., Moreno-Navarrete, J.M., and Fernández-Real, J.M. (2022). The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism. Nat Rev Endocrinol 18, 683–698.

    Article  CAS  PubMed  Google Scholar 

  • Mazmanian, S.K., Skaar, E.P., Gaspar, A.H., Humayun, M., Gornicki, P., Jelenska, J., Joachmiak, A., Missiakas, D.M., and Schneewind, O. (2003). Passage of heme-iron across the envelope of Staphylococcus aureus. Science 299, 906–909.

    Article  CAS  PubMed  Google Scholar 

  • McKie, A.T., Barrow, D., Latunde-Dada, G.O., Rolfs, A., Sager, G., Mudaly, E., Mudaly, M., Richardson, C., Barlow, D., Bomford, A., et al. (2001). An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291, 1755–1759.

    Article  CAS  PubMed  Google Scholar 

  • McPherson, C.J., Aschenbrenner, L.M., Lacey, B.M., Fahnoe, K.C., Lemmon, M.M., Finegan, S.M., Tadakamalla, B., O’Donnell, J.P., Mueller, J.P., and Tomaras, A.P. (2012). Clinically relevant Gramnegative resistance mechanisms have no effect on the efficacy of MC-1, a novel siderophore-conjugated monocarbam. Antimicrob Agents Chemother 56, 6334–6342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehri, A. (2020). Trace elements in human nutrition (II)—an update. Int J Prev Med 11, 2.

    PubMed  PubMed Central  Google Scholar 

  • Melkebeek, V., Rasschaert, K., Bellot, P., Tilleman, K., Favoreel, H., Deforce, D., De Geest, B.G., Goddeeris, B.M., and Cox, E. (2012). Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response. Mucosal Immunol 5, 635–645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng, X.L., Li, S., Qin, C.B., Zhu, Z.X., Hu, W.P., Yang, L.P., Lu, R.H., Li, W.J., and Nie, G.X. (2018). Intestinal microbiota and lipid metabolism responses in the common carp (Cyprinus carpio L.) following copper exposure. Ecotoxicol Environ Saf 160, 257–264.

    Article  CAS  PubMed  Google Scholar 

  • Mevissen-Verhage, E.A.E., Marcelis, J.H., Harmsen-Van Amerongen, W.C. M., de Vos, N.M., and Verhoef, J. (1985). Effect of iron on neonatal gut flora during the first three months of life. Eur J Clin Microbiol 4, 273–278.

    Article  CAS  PubMed  Google Scholar 

  • Miethke, M., and Marahiel, M.A. (2007). Siderophore-based iron acquisition and pathogen control. Microbiol Mol Biol Rev 71, 413–451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller, K.A., Vicentini, F.A., Hirota, S.A., Sharkey, K.A., and Wieser, M.E. (2019). Antibiotic treatment affects the expression levels of copper transporters and the isotopic composition of copper in the colon of mice. Proc Natl Acad Sci USA 116, 5955–5960.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mokgobu, M.I., Anderson, R., Steel, H.C., Cholo, M.C., Tintinger, G.R., and Theron, A.J. (2012). Manganese promotes increased formation of hydrogen peroxide by activated human macrophages and neutrophils in vitro. Inhal Toxicol 24, 634–644.

    Article  CAS  PubMed  Google Scholar 

  • Mortensen, B.L., Rathi, S., Chazin, W.J., and Skaar, E.P. (2014). Acinetobacter baumannii response to host-mediated zinc limitation requires the transcriptional regulator Zur. J Bacteriol 196, 2616–2626.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mortensen, B.L., and Skaar, E.P. (2013). The contribution of nutrient metal acquisition and metabolism to Acinetobacter baumannii survival within the host. Front Cell Infect Microbiol 3, 95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mu, C., and Zhu, W. (2019). Antibiotic effects on gut microbiota, metabolism, and beyond. Appl Microbiol Biotechnol 103, 9277–9285.

    Article  CAS  PubMed  Google Scholar 

  • Muñoz, M., Villar, I., and García-Erce, J.A. (2009). An update on iron physiology. World J Gastroenterol 15, 4617–4626.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nargund, S., Qiu, J., and Goudar, C.T. (2015). Elucidating the role of copper in CHO cell energy metabolism using 13C metabolic flux analysis. Biotechnol Prog 31, 1179–1186.

    Article  CAS  PubMed  Google Scholar 

  • Neumann, W., Sassone-Corsi, M., Raffatellu, M., and Nolan, E.M. (2018). Esterase-catalyzed siderophore hydrolysis activates an enterobactin-ciprofloxacin conjugate and confers targeted antibacterial activity. J Am Chem Soc 140, 5193–5201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ong, C.Y., Berking, O., Walker, M.J., and McEwan, A.G. (2018). New insights into the role of zinc acquisition and zinc tolerance in group a streptococcal infection. Infect Immun 86, e00048–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pallauf, J., Kauer, C., Most, E., Habicht, S.D., and Moch, J. (2012). Impact of dietary manganese concentration on status criteria to determine manganese requirement in piglets. J Anim Physiol Anim Nutr 96, 993–1002.

    Article  CAS  Google Scholar 

  • Palmiter, R.D. (2004). Protection against zinc toxicity by metallothionein and zinc transporter 1. Proc Natl Acad Sci USA 101, 4918–4923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palmiter, R.D., and Findley, S.D. (1995). Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J 14, 639–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papp-Wallace, K.M., and Maguire, M.E. (2006). Manganese transport and the role of manganese in virulence. Annu Rev Microbiol 60, 187–209.

    Article  CAS  PubMed  Google Scholar 

  • Pickard, J.M., Zeng, M.Y., Caruso, R., and Núñez, G. (2017). Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev 279, 70–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poduval, R.D., Kamath, R.P., Corpuz, M., Norkus, E.P., and Pitchumoni, C. S. (2000). Clostridium difficile and vancomycin-resistant enterococcus: the new nosocomial alliance. Am J Gastroenterol 95, 3513–3515.

    Article  CAS  PubMed  Google Scholar 

  • Posey, J.E., and Gherardini, F.C. (2000). Lack of a role for iron in the Lyme disease pathogen. Science 288, 1651–1653.

    Article  CAS  PubMed  Google Scholar 

  • Potelle, S., Dulary, E., Climer, L., Duvet, S., Morelle, W., Vicogne, D., Lebredonchel, E., Houdou, M., Spriet, C., Krzewinski-Recchi, M.A., et al. (2017). Manganese-induced turnover of TMEM165. Biochem J 474, 1481–1493.

    Article  CAS  PubMed  Google Scholar 

  • Potelle, S., Morelle, W., Dulary, E., Duvet, S., Vicogne, D., Spriet, C., Krzewinski-Recchi, M.A., Morsomme, P., Jaeken, J., Matthijs, G., et al. (2016). Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis. Hum Mol Genet 25, 1489–1500.

    Article  CAS  PubMed  Google Scholar 

  • Puri, S., Kumar, R., Rojas, I.G., Salvatori, O., and Edgerton, M. (2019). Iron chelator deferasirox reduces Candida albicans invasion of oral epithelial cells and infection levels in murine oropharyngeal candidiasis. Antimicrob Agents Chemother 63, e02152–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pyle, C.J., Akhter, S., Bao, S.Y., Dodd, C.E., Schlesinger, L.S., and Knoell, D.L. (2017). Zinc modulates endotoxin-induced human macrophage inflammation through ZIP8 induction and C/EBPβ inhibition. PLoS ONE 12, e0169531.

    Article  PubMed  PubMed Central  Google Scholar 

  • Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K.S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., et al. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rakin, A., Schneider, L., and Podladchikova, O. (2012). Hunger for iron: the alternative siderophore iron scavenging systems in highly virulent Yersinia. Front Cell Inf Microbio 2, 151.

    Article  Google Scholar 

  • Ran, C., Li, Y., Ma, X., Xie, Y., Xie, M., Zhang, Y., Zhou, W., Yang, Y., Zhang, Z., Zhou, L., et al. (2021). Interactions between commensal bacteria and viral infection: insights for viral disease control in farmed animals. Sci China Life Sci 64, 1437–1448.

    Article  PubMed  Google Scholar 

  • Reed, S., Neuman, H., Moscovich, S., Glahn, R., Koren, O., and Tako, E. (2015). Chronic zinc deficiency alters chick gut microbiota composition and function. Nutrients 7, 9768–9784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren, W., Yu, B., Yu, J., Zheng, P., Huang, Z., Luo, J., Mao, X., He, J., Yan, H., Wu, J., et al. (2022). Lower abundance of Bacteroides and metabolic dysfunction are highly associated with the post-weaning diarrhea in piglets. Sci China Life Sci 65, 2062–2075.

    Article  CAS  PubMed  Google Scholar 

  • Ren, X., Li, Y., Zhou, Y., Hu, W., Yang, C., Jing, Q., Zhou, C., Wang, X., Hu, J., Wang, L., et al. (2021). Overcoming the compensatory elevation of NRF2 renders hepatocellular carcinoma cells more vulnerable to disulfiram/copper-induced ferroptosis. Redox Biol 46, 102122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rouault, T.A. (2005). The intestinal heme transporter revealed. Cell 122, 649–651.

    Article  CAS  PubMed  Google Scholar 

  • Saha, P., Yeoh, B.S., Xiao, X., Golonka, R.M., Abokor, A.A., Wenceslau, C.F., Shah, Y.M., Joe, B., and Vijay-Kumar, M. (2020). Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron. Gut Microbes 12, 1841548.

    Article  PubMed  PubMed Central  Google Scholar 

  • Saha, S., Shalova, I.N., and Biswas, S.K. (2017). Metabolic regulation of macrophage phenotype and function. Immunol Rev 280, 102–111.

    Article  CAS  PubMed  Google Scholar 

  • Salovaara, S., Sandberg, A.S., and Andlid, T. (2003). Combined impact of pH and organic acids on iron uptake by Caco-2 cells. J Agric Food Chem 51, 7820–7824.

    Article  CAS  PubMed  Google Scholar 

  • Schaible, U.E., Collins, H.L., Priem, F., and Kaufmann, S.H.E. (2002). Correction of the iron overload defect in β-2-microglobulin knockout mice by lactoferrin abolishes their increased susceptibility to tuberculosis. J Exp Med 196, 1507–1513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schalk, I.J., and Guillon, L. (2013). Fate of ferrisiderophores after import across bacterial outer membranes: different iron release strategies are observed in the cytoplasm or periplasm depending on the siderophore pathways. Amino Acids 44, 1267–1277.

    Article  CAS  PubMed  Google Scholar 

  • Science, M., Johnstone, J., Roth, D.E., Guyatt, G., and Loeb, M. (2012). Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 184, E551–E561.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sestok, A.E., Linkous, R.O., and Smith, A.T. (2018). Toward a mechanistic understanding of Feo-mediated ferrous iron uptake. Metallomics 10, 887–898.

    Article  CAS  PubMed  Google Scholar 

  • Seyoum, Y., Baye, K., and Humblot, C. (2021). Iron homeostasis in host and gut bacteria—a complex interrelationship. Gut Microbes 13, 1–9.

    Article  CAS  PubMed  Google Scholar 

  • Shah, Y.M., Matsubara, T., Ito, S., Yim, S.H., and Gonzalez, F.J. (2009). Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab 9, 152–164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shannon, M.C., and Hill, G.M. (2019). Trace mineral supplementation for the intestinal health of young monogastric animals. Front Vet Sci 6, 73.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shao, Y., Lei, Z., Yuan, J., Yang, Y., Guo, Y., and Zhang, B. (2014). Effect of zinc on growth performance, gut morphometry, and cecal microbial community in broilers challenged with Salmonella enterica serovar typhimurium. J Microbiol 52, 1002–1011.

    Article  CAS  PubMed  Google Scholar 

  • Shao, Y., Wolf, P.G., Guo, S., Guo, Y., Gaskins, H.R., and Zhang, B. (2017). Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells. J Nutral Biochem 43, 18–26.

    Article  CAS  Google Scholar 

  • Shawki, A., Anthony, S.R., Nose, Y., Engevik, M.A., Niespodzany, E.J., Barrientos, T., Öhrvik, H., Worrell, R.T., Thiele, D.J., and Mackenzie, B. (2015). Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese. Am J Physiol Gastrointest Liver Physiol 309, G635–G647.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sheldon, J.R., Laakso, H.A., and Heinrichs, D.E. (2016). Iron acquisition strategies of bacterial pathogens. Microbiol Spectr 4, 4.2.05.

    Article  Google Scholar 

  • Sitkin, S.I., Tkachenko, E.I., and Vakhitov, T.Y. (2016). Metabolic dysbiosis of the gut microbiota and its biomarkers. Exp Clin Gastroenterol 12, 6–29.

    CAS  Google Scholar 

  • Skaar, E.P., and Schneewind, O. (2004). Iron-regulated surface determinants (Isd) of Staphylococcus aureus: stealing iron from heme. Microbes Infect 6, 390–397.

    Article  CAS  PubMed  Google Scholar 

  • Soares, M.P., and Hamza, I. (2016). Macrophages and Iron Metabolism. Immunity 44, 492–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, M., Li, X., Zhang, X., Shi, H., Vos, M.B., Wei, X., Wang, Y., Gao, H., Rouchka, E.C., Yin, X., et al. (2018). Dietary copper-fructose interactions alter gut microbial activity in male rats. Am J Physiol Gastrointest Liver Physiol 314, G119–G130.

    Article  PubMed  Google Scholar 

  • Song, M., Yuan, F., Li, X., Ma, X., Yin, X., Rouchka, E.C., Zhang, X., Deng, Z., Prough, R.A., and McClain, C.J. (2021). Analysis of sex differences in dietary copper-fructose interaction-induced alterations of gut microbial activity in relation to hepatic steatosis. Biol Sex Differ 12, 3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, M.O., and Freedman, J.H. (2011). Role of hepatocyte nuclear factor 4α in controlling copper-responsive transcription. Biochim Biophys Acta 1813, 102–108.

    Article  CAS  PubMed  Google Scholar 

  • Song, R., Wang, Y., Zheng, Q., Yao, J., Cao, C., Wang, Y., and Zhao, J. (2022). One-step base editing in multiple genes by direct embryo injection for pig trait improvement. Sci China Life Sci 65, 739–752.

    Article  CAS  PubMed  Google Scholar 

  • Souffriau, J., Timmermans, S., Vanderhaeghen, T., Wallaeys, C., Van Looveren, K., Aelbrecht, L., Dewaele, S., Vandewalle, J., Goossens, E., Verbanck, S., et al. (2020). Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium. EMBO Mol Med 12, e11917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sousa Gerós, A., Simmons, A., Drakesmith, H., Aulicino, A., and Frost, J. N. (2020). The battle for iron in enteric infections. Immunology 161, 186–199.

    Article  PubMed  PubMed Central  Google Scholar 

  • Squizani, S., Jantsch, J., Rodrigues, F.S., Braga, M.F., Eller, S., de Oliveira, T.F., Silveira, A.K., Moreira, J.C.F., Giovenardi, M., Porawski, M., et al. (2022). Zinc supplementation partially decreases the harmful effects of a cafeteria diet in rats but does not prevent intestinal dysbiosis. Nutrients 14, 3921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Summersgill, H., England, H., Lopez-Castejon, G., Lawrence, C.B., Luheshi, N.M., Pahle, J., Mendes, P., and Brough, D. (2014). Zinc depletion regulates the processing and secretion of IL-1β. Cell Death Dis 5, e1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taniguchi, M., Fukunaka, A., Hagihara, M., Watanabe, K., Kamino, S., Kambe, T., Enomoto, S., and Hiromura, M. (2013). Essential role of the zinc transporter ZIP9/SLC39A9 in regulating the activations of Akt and Erk in B-cell receptor signaling pathway in DT40 cells. PLoS ONE 8, e58022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor, M., Qu, A., Anderson, E.R., Matsubara, T., Martin, A., Gonzalez, F. J., and Shah, Y.M. (2011). Hypoxia-inducible factor-2α mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice. Gastroenterology 140, 2044–2055.

    Article  CAS  PubMed  Google Scholar 

  • Thaiss, C.A., Zmora, N., Levy, M., and Elinav, E. (2016). The microbiome and innate immunity. Nature 535, 65–74.

    Article  CAS  PubMed  Google Scholar 

  • Tinkov, A.A., Martins, A.C., Avila, D.S., Gritsenko, V.A., Skalny, A.V., Santamaria, A., Lee, E., Bowman, A.B., and Aschner, M. (2021). Gut microbiota as a potential player in Mn-induced neurotoxicity. Biomolecules 11, 1292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tree, J.J., Kidd, S.P., Jennings, M.P., and McEwan, A.G. (2005). Copper sensitivity of cueO mutants of Escherichia coli K-12 and the biochemical suppression of this phenotype. Biochem Biophys Res Commun 328, 1205–1210.

    Article  CAS  PubMed  Google Scholar 

  • Villagómez-Estrada, S., Pérez, J.F., Darwich, L., Vidal, A., van Kuijk, S., Melo-Durán, D., and Solà-Oriol, D. (2020). Effects of copper and zinc sources and inclusion levels of copper on weanling pig performance and intestinal microbiota. J anim Sci 98, skaa117.

    Article  PubMed  PubMed Central  Google Scholar 

  • Waldron, K.J., Rutherford, J.C., Ford, D., and Robinson, N.J. (2009). Metalloproteins and metal sensing. Nature 460, 823–830.

    Article  CAS  PubMed  Google Scholar 

  • Wang, C., Guan, Y., Lv, M., Zhang, R., Guo, Z., Wei, X., Du, X., Yang, J., Li, T., Wan, Y., et al. (2018). Manganese increases the sensitivity of the cGAS-STING pathway for double-stranded DNA and is required for the host defense against DNA viruses. Immunity 48, 675–687.e7.

    Article  CAS  PubMed  Google Scholar 

  • Wang, Y., Wang, H., Wang, B., Zhang, B., and Li, W. (2020). Effects of manganese and Bacillus subtilis on the reproductive performance, egg quality, antioxidant capacity, and gut microbiota of breeding geese during laying period. Poult Sci 99, 6196–6204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weinberg, E.D. (1997). The lactobacillus anomaly: total iron abstinence. Perspect Biol Med 40, 578–583.

    Article  CAS  PubMed  Google Scholar 

  • Wen, J., Zheng, Z., Gong, M., Li, D., Hu, S., Cai, Y., Wang, Y., Nanaei, H. A., Zhang, N., Yu, T., et al. (2022). Ancient genomes reveal the genetic inheritance and recent introgression in Chinese indigenous pigs. Sci China Life Sci 65, 842–845.

    Article  CAS  PubMed  Google Scholar 

  • Wessells, K.R., and Brown, K.H. (2012). Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS ONE 7, e50568.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wolff, N.A., Garrick, M.D., Zhao, L., Garrick, L.M., Ghio, A.J., and Thévenod, F. (2018). A role for divalent metal transporter (DMT1) in mitochondrial uptake of iron and manganese. Sci Rep 8, 211.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wong, C.P., Rinaldi, N.A., and Ho, E. (2015). Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation. Mol Nutr Food Res 59, 991–999.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia, P., Quan, G., Yang, Y., Zhao, J., Wang, Y., Zhou, M., Hardwidge, P.R., Zhu, J., Liu, S., and Zhu, G. (2018). Binding determinants in the interplay between porcine aminopeptidase N and enterotoxigenic Escherichia coli F4 fimbriae. Vet Res 49, 23.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xia, Z., Wei, J., Li, Y., Wang, J., Li, W., Wang, K., Hong, X., Zhao, L., Chen, C., Min, J., et al. (2017). Zebrafish slc30a10 deficiency revealed a novel compensatory mechanism of atp2c1 in maintaining manganese homeostasis. PLoS Genet 13, e1006892.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xiang, H., Chen, S., Zhang, H., Zhu, X., Wang, D., Liu, H., Wang, J., Yin, T., Liu, L., Kong, M., et al. (2021). Removal of roosters alters the domestic phenotype and microbial and genetic profile of hens. Sci China Life Sci 64, 1964–1976.

    Article  CAS  PubMed  Google Scholar 

  • Yan, G., Liu, X., Xiao, S., Xin, W., Xu, W., Li, Y., Huang, T., Qin, J., Xie, L., Ma, J., et al. (2022). An imputed whole-genome sequence-based GWAS approach pinpoints causal mutations for complex traits in a specific swine population. Sci China Life Sci 65, 781–794.

    Article  CAS  PubMed  Google Scholar 

  • Yang, Y., Song, X., Chen, A., Wang, H., and Chai, L. (2020). Exposure to copper altered the intestinal microbiota in Chinese brown frog (Rana chensinensis). Environ Sci Pollut Res 27, 13855–13865.

    Article  CAS  Google Scholar 

  • Yu, Z., Zhou, R., Zhao, Y., Pan, Y., Liang, H., Zhang, J.S., Tai, S., Jin, L., and Teng, C.B. (2019). Blockage of SLC31A1-dependent copper absorption increases pancreatic cancer cell autophagy to resist cell death. Cell Prolif 52, e12568.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zackular, J.P., Moore, J.L., Jordan, A.T., Juttukonda, L.J., Noto, M.J., Nicholson, M.R., Crews, J.D., Semler, M.W., Zhang, Y., Ware, L.B., et al. (2016). Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection. Nat Med 22, 1330–1334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zackular, J.P., and Skaar, E.P. (2018). The role of zinc and nutritional immunity in Clostridium difficile infection. Gut Microbes 9, 469–476.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zaharik, M.L., and Finlay, B.B. (2004). Mn2+ and bacterial pathogenesis. Front Biosci 9, 1035–1042.

    Article  CAS  PubMed  Google Scholar 

  • Zeinert, R., Martinez, E., Schmitz, J., Senn, K., Usman, B., Anantharaman, V., Aravind, L., and Waters, L.S. (2018). Structure-function analysis of manganese exporter proteins across bacteria. J Biol Chem 293, 5715–5730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhanel, G.G., Golden, A.R., Zelenitsky, S., Wiebe, K., Lawrence, C.K., Adam, H.J., Idowu, T., Domalaon, R., Schweizer, F., Zhanel, M.A., et al. (2019). Cefiderocol: a siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant Gram-negative bacilli. Drugs 79, 271–289.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, C. (2014). Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control. Protein Cell 5, 750–760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, C., Sui, D., Zhang, T., and Hu, J. (2020). Molecular basis of zinc-dependent endocytosis of human ZIP4 transceptor. Cell Rep 31, 107582.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y., Sun, Y., Wu, Z., Xiong, X., Zhang, J., Ma, J., Xiao, S., Huang, L., and Yang, B. (2021). Subcutaneous and intramuscular fat transcriptomes show large differences in network organization and associations with adipose traits in pigs. Sci China Life Sci 64, 1732–1746.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, B., Tang, Y., Zhang, B., Wu, P., Li, M., Xu, X., Wu, G., Jiang, H., and Chen, Y. (2020). The temperature-dependent retention of introns in GPI8 transcripts contributes to a drooping and fragile shoot phenotype in rice. Int J Mol Sci 21, 299.

    Article  CAS  Google Scholar 

  • Zheng, Y.Y., Ma, Y.T., Zhang, J.Y., and Xie, X. (2020). COVID-19 and the cardiovascular system. Nat Rev Cardiol 17, 259–260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu, Y., Zhou, Z., Huang, T., Zhang, Z., Li, W., Ling, Z., Jiang, T., Yang, J., Yang, S., Xiao, Y., et al. (2022). Mapping and analysis of a spatiotemporal H3K27ac and gene expression spectrum in pigs. Sci China Life Sci 65, 1517–1534.

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann, M.B., and Hurrell, R.F. (2007). Nutritional iron deficiency. Lancet 370, 511–520.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (31772642, 31672457), Ministry of Agricultural of the People’s Republic of China (2015-Z64, 2016-X47), Hunan Provincial Science and Technology Department (2021J30008, 2019TP2004, 2017NK2322, 2016WK2008, 2016TP2005), Double first-class construction project of Hunan Agricultural University (SYL201802003), China Postdoctoral Science Foundation (2018M632963, 2019T120705), Postgraduate Scientific Research Innovation Project of Hunan Province (CX20210654) and Science and Technology Innovation and Entrepreneurship Project for University Students of Hunan Province (2021RC1004).

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  1. College of Bioscience and Biotechnology, Hunan Agricultural University, Hunan Provincial Engineering Research Center of Applied Microbial Resources Development for Livestock and Poultry, Changsha, 410128, China

    Yong Ma, Yanquan Fei, Sujuan Ding, Hongmei Jiang, Jun Fang & Gang Liu

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  1. Yong Ma
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  2. Yanquan Fei
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  5. Jun Fang
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Correspondence to Jun Fang.

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Ma, Y., Fei, Y., Ding, S. et al. Trace metal elements: a bridge between host and intestinal microorganisms. Sci. China Life Sci. 66, 1976–1993 (2023). https://doi.org/10.1007/s11427-022-2359-4

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