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Chitosan-chelated zinc modulates cecal microbiota and attenuates inflammatory response in weaned rats challenged with Escherichia coli

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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Abstract

Escherichia coli (E. coli) infection is very common among young growing animals, and zinc supplementation is often used to alleviate inflammation induced by this disease. Therefore, the objective of this study was to evaluate whether chitosan-chelated zinc (CS-Zn) supplementation could attenuate gut injury induced by E. coli challenge and to explore how CS-Zn modulates cecal microbiota and alleviates intestinal inflammation in weaned rats challenged with E. coli. 36 weaned rats (55.65 ± 2.18 g of BW, n = 12) were divided into three treatment groups consisting of unchallenged rats fed a basal diet (Control) and two groups of rats challenged with E. coli and fed a basal diet or a diet containing 640 mg/kg CS-Zn (E. coli + CS-Zn, containing 50 mg/kg Zn) for a 14-day experiment. On days 10 to 12, each rat was given 4 ml of E. coli solution with a total bacteria count of 1010 CFU by oral gavage daily or normal saline of equal dosage. CS-Zn supplementation mitigated intestinal morphology impairment (e.g. higher crypt depth and lower macroscopic damage index) induced by E. coli challenge (P < 0.05), and alleviated the increase of Myeloperoxidase (MPO) activity after E. coli challenge (P < 0.05). 16S rRNA sequencing analyses revealed that E. coli challenge significantly increased the abundance of Verrucomicrobia and E. coli (P < 0.05). However, CS-Zn supplementation increased the abundance of Lactobacillus and decreased the relative abundance of Proteobacteria, Desulfovibrio and E. coli (P < 0.05). The concentrations of butyrate in the cecal digesta, which decreased due to the challenge, were higher in the E. coli + CS-Zn group (P < 0.05). In addition, CS-Zn supplementation significantly prevented the elevation of pro-inflammatory cytokines IL-6 concentration and up-regulated the level of anti-inflammatory cytokines IL-10 in cecal mucosa induced by E. coli infection (P < 0.05). In conclusion, these results indicate that CS-Zn produces beneficial effects in alleviating gut mucosal injury of E. coli challenged rats by enhancing the intestinal morphology and modulating cecal bacterial composition, as well as attenuating inflammatory response.

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References

  • Aβhauer, K.P., Wemheuer, B., Daniel, R., and Meinicke, P. 2015. Tax4Fun: predicting functional profiles from metagenomic 16S rRNA data. Bioinformatics 31, 2882–2884.

    Google Scholar 

  • Alhussien, M.N. and Dang, A.K. 2018. Pathogen-dependent modulation of milk neutrophils competence, plasma inflammatory cytokines and milk quality during intramammary infection of Sahiwal (Bos indicus) cows. Microb. Pathog. 121, 131–138.

    PubMed  CAS  Google Scholar 

  • Balamurugan, R., Rajendiran, E., George, S., Vijay Samuel, G., and Ramakrishna, B.S. 2010. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J. Gastroenterol. Hepatol. 23, 1298–1303.

    Google Scholar 

  • Bäumler, A.J. and Sperandio, V. 2016. Interactions between the microbiota and pathogenic bacteria in the gut. Nature 535, 85–93.

    PubMed  PubMed Central  Google Scholar 

  • Belzer, C. and de Vos, W.M. 2012. Microbes inside-from diversity to function: the case of Akkermansia. ISME J. 6, 1449–1458.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Bilić-Šobot, D., Kubale, V., Škrlep, M., Čandek-Potokar, M., Prevolnik Povše, M., Fazarinc, G., and Škorjanc, D. 2016. Effect of hydrolysable tannins on intestinal morphology, proliferation and apoptosis in entire male pigs. Arch. Anim. Nutr. 70, 378–388.

    PubMed  Google Scholar 

  • Bourgault, A.M., Rosenblatt, J.E., and Fitzgerald, R.H. 1980. Peptococcus magnus: a significant human pathogen}. Ann. Intern. Med. 93, 244–248.

    PubMed  CAS  Google Scholar 

  • Caporaso, J.G., Lauber, C.L., Walters, W.A., Berg-Lyons, D., Huntley, J., Fierer, N., Owens, S.M., Betley, J., Fraser, L., Bauer, M., et al. 2012. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 6, 1621–1624.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Derrien, M., van Passel, M.W., van de Bovenkamp, J.H.B., Schipper, R.G., de Vos, W.M., and Dekker, J. 2010. Mucin-bacterial interactions in the human oral cavity and digestive tract. Gut Microbes 1, 254–268.

    PubMed  PubMed Central  Google Scholar 

  • Di Lorenzo, F., de Castro, C., Silipo, A., and Molinaro, A. 2019. Lipopolysaccharide structures of Gram-negative populations in the gut microbiota and effects on host interactions. FEMS Microbiol. Rev. 43, 257–272.

    PubMed  CAS  Google Scholar 

  • Dinan, T.G. and Cryan, J.F. 2012. Regulation of the stress response by the gut microbiota: implications for psychoneuroendocrinology. Psychoneuroendocrinology 37, 1369–1378.

    PubMed  CAS  Google Scholar 

  • Edgar, R.C. 2013. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat. Methods 10, 996–998.

    PubMed  CAS  Google Scholar 

  • Ewaschuk, J.B., Murdoch, G.K., Johnson, I.R., Madsen, K.L., and Field, C.J. 2011. Glutamine supplementation improves intestinal barrier function in a weaned piglet model of Escherichia coli infection. Br. J. Nutr. 106, 870–877.

    PubMed  CAS  Google Scholar 

  • Florin, T., Neale, G., Gibson, G., Christl, S., and Cummings, J. 1991. Metabolism of dietary sulphate: absorption and excretion in humans. Gut 32, 766–773.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Fosmire, G.J. 1990. Zinc toxicity. Am. J. Clin. Nutr. 51, 225–227.

    PubMed  CAS  Google Scholar 

  • Fujio-Vejar, S., Vasquez, Y., Morales, P., Magne, F., Vera-Wolf, P., Ugalde, J.A., Navarrete, P., and Gotteland, M. 2017. The gut microbiota of healthy chilean subjects reveals a high abundance of the phylum Verrucomicrobia. Front. Microbiol. 8, 1221.

    PubMed  PubMed Central  Google Scholar 

  • Gensollen, T., Iyer, S.S., Kasper, D.L., and Blumberg, R.S. 2016. How colonization by microbiota in early life shapes the immune system. Science 352, 539–544.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Gerritsen, J., Fuentes, S., Grievink, W., van Niftrik, L., Tindall, B.J., Timmerman, H.M., Rijkers, G.T., and Smidt, H. 2014. Characterization of Romboutsia ilealis gen. nov., sp. nov., isolated from the gastro-intestinal tract of a rat, and proposal for the reclassification of five closely related members of the genus Clostridium into the genera Romboutsia gen. nov., Intestinibacter gen. nov., Terrisporobacter gen. nov. and Asaccharospora gen. nov}. Int. J. Syst. Evol. Microbiol. 64, 1600–1616.

    PubMed  CAS  Google Scholar 

  • Glenny, E.M., Bulik-Sullivan, E.C., Tang, Q., Bulik, C.M., and Carroll, I.M. 2017. Eating disorders and the intestinal microbiota: mechanisms of energy homeostasis and behavioral influence. Curr. Psychiatry Rep. 19, 51.

    PubMed  PubMed Central  Google Scholar 

  • Goiri, I., Oregui, L.M., and Garcia-Rodriguez, A. 2010. Use of chitosans to modulate ruminal fermentation of a 50:50 forage-to-concentrate diet in sheep. J. Anim. Sci. 88, 749–755.

    PubMed  CAS  Google Scholar 

  • Han, X.Y., Ma, Y.F., Lv, M.Y., Wu, Z.P., and Qian, L.C. 2014. Chitosan-zinc chelate improves intestinal structure and mucosal function and decreases apoptosis in ileal mucosal epithelial cells in weaned pigs. Br. J. Nutr. 111, 1405–1411.

    PubMed  CAS  Google Scholar 

  • Hooper, L.V., Wong, M.H., Thelin, A., Hansson, L., Falk, P.G., and Gordon, J.I. 2001. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291, 881–884.

    PubMed  CAS  Google Scholar 

  • Jacobson, M., Segerstad, C.H.A., Gunnarsson, A., Fellström, C., de Verdier Klingenberg, K., Wallgren, P., and Jensen-Waern, M. 2003. Diarrhoea in the growing pig — a comparison of clinical, morphological and microbial findings between animals from good and poor performance herds. Res. Vet. Sci. 74, 163–169.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Janczyk, P., Kreuzer, S., Assmus, J., Nöckler, K., and Brockmann, G.A. 2013. No protective effects of high-dosage dietary zinc oxide on weaned pigs infected with Salmonella enterica serovar Typhimurium DT104. Appl. Environ. Microbiol. 79, 2914–2921.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Jiang, N., Liu, H., Wang, P., Huang, J., Han, H., and Wang, Q. 2019. Illumina MiSeq sequencing investigation of microbiota in bronchoalveolar lavage fluid and cecum of the swine infected with PRRSV. Curr. Microbiol. 76, 222–230.

    PubMed  CAS  Google Scholar 

  • Jussi, V., Erkki, E., and Paavo, T. 2005. Comparison of cellular fatty acid profiles of the microbiota in different gut regions of BALB/c and C57BL/6J mice. Antonie van Leeuwenhoek 88, 67–74.

    PubMed  CAS  Google Scholar 

  • Kim, J.M., Oh, Y.K., Kim, Y.J., Youn, J., and Ahn, M.J. 2004. Escherichia coli up-regulates proinflammatory cytokine expression in granulocyte/macrophage lineages of CD34 stem cells via p50 homodimeric NF-kB. Clin. Exp. Immunol. 137, 341–350.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Kushkevych, I., Vítězová, M., Fedrová, P., Vochyanová, Z., Pará-ková, L., and Hošek, J. 2017. Kinetic properties of growth of intestinal sulphate-reducing bacteria isolated from healthy mice and mice with ulcerative colitis. Acta Vet. Brno 86, 405–411.

    Google Scholar 

  • Lai, R.H. 2009. Ph. D. thesis. University of Illinois, Urbana-Champaign, Champaign, USA.

    Google Scholar 

  • Lehri, B., Seddon, A.M., and Karlyshev, A.V. 2017. Lactobacillus fermentum 3872 as a potential tool for combatting Campylobacter jejuni infections}. Virulence 8, 1753–1760.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Li, S., Qi, Y., Chen, L., Qu, D., Li, Z., Gao, K., Chen, J., and Sun, Y. 2019. Effects of Panax ginseng polysaccharides on the gut microbiota in mice with antibiotic-associated diarrhea. Int. J. Biol. Macromol. 124, 931–937.

    PubMed  CAS  Google Scholar 

  • Ma, Y., Huang, Q., Lv, M., Wu, Z., Xie, Z., Han, X., and Wang, Y. 2014. Chitosan-Zn chelate increases antioxidant enzyme activity and improves immune function in weaned piglets. Biol. Trace Elem. Res. 158, 45–50.

    PubMed  CAS  Google Scholar 

  • Macpherson, A.J., Yilmaz, B., Limenitakis, J.P., and Ganal-Vonarburg, S.C. 2018. IgA function in relation to the intestinal microbiota. Annu. Rev. Immunol. 36, 359–381.

    PubMed  CAS  Google Scholar 

  • Nagano, K., Taguchi, K., Hara, T., Yokoyama, S., Kawada, K., and Mori, H. 2013. Adhesion and colonization of enterohemorrhagic Escherichia coli O157:H7 in cecum of mice. Microbiol. Immunol. 47, 125–132.

    Google Scholar 

  • Nettelbladt, C.G., Katouli, M., Bark, T., Svenberg, T., Möllby, R., and Ljungqvist, O. 2003. Orally inoculated Escherichia coli strains colonize the gut and increase bacterial translocation after stress in rats. Shock 20, 251–256.

    PubMed  Google Scholar 

  • Parks, D.H., Tyson, G.W., Hugenholtz, P., and Beiko, R.G. 2014. STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics 30, 3123–3124.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Partula, V., Mondot, S., Torres, M.J., Kesse-Guyot, E., Deschasaux, M., Assmann, K., Latino-Martel, P., Buscail, C., Julia, C., Galan, P., et al. 2019. Associations between usual diet and gut microbiota composition: results from the Milieu Intérieur cross-sectional study. Am. J. Clin. Nutr. 109, 1472–1483.

    PubMed  Google Scholar 

  • Pi, Y., Gao, K., Peng, Y., Mu, C.L., and Zhu, W.Y. 2018. Antibiotic-induced alterations of the gut microbiota and microbial fermentation in protein parallel the changes in host nitrogen metabolism of growing pigs. Animal 13, 262–272.

    PubMed  Google Scholar 

  • Polansky, O., Sekelova, Z., Faldynova, M., Sebkova, A., Sisak, F., and Rychlik, I. 2016. Important metabolic pathways and biological processes expressed by chicken cecal microbiota. Appl. Environ. Microbiol. 82, 1569–1576.

    PubMed Central  CAS  Google Scholar 

  • Rhee, K.J., Cheng, H., Harris, A., Morin, C., Kaper, J.B., and Hecht, G. 2011. Determination of spatial and temporal colonization of enteropathogenic E. coli and enterohemorrhagic E. coli in mice using bioluminescent in vivo} imaging}. Gut Microbes 2, 34–41.

    PubMed  PubMed Central  Google Scholar 

  • Rizzatti, G., Lopetuso, L.R., Gibiino, G., Binda, C., and Gasbarrini, A. 2017. Proteobacteria: a common factor in human diseases. BioMed Res. Int. 2017, 9351507.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Roediger, W., Moore, J., and Babidge, W. 1997. Colonic sulfide in pathogenesis and treatment of ulcerative colitis. Dig. Dis. Sci. 42, 1571–1579.

    PubMed  CAS  Google Scholar 

  • Roxas, J.L., Koutsouris, A., Bellmeyer, A., Tesfay, S., Royan, S., Falzari, K., Harris, A., Cheng, H., Rhee, K.J., and Hecht, G. 2010. Enterohemorrhagic E. coli alters murine intestinal epithelial tight junction protein expression and barrier function in a Shiga toxin independent manner. Lab Invest. 90, 1152–1168.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Roy, C.C., Kien, C.L., Bouthillier, L., and Levy, E. 2006. Short-chain fatty acids: ready for prime time? Nutr. Clin. Pract. 21, 351–366.

    PubMed  Google Scholar 

  • Sampaio, S.C., Moreira, F.C., Liberatore, A.M., Vieira, M.A., Knobl, T., Romão, F.T., Hernandes, R.T., Ferreira, C.S., Ferreira, A.P., Felipe-Silva, A., et al. 2014. Analysis of the virulence of an atypical enteropathogenic Escherichia coli strain in vitro and in vivo and the influence of type three secretion system. BioMed. Res. Int. 2014, 797508.

    PubMed  PubMed Central  Google Scholar 

  • Shin, N.R., Whon, T.W., and Bae, J.W. 2015. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol. 33, 496–50

    PubMed  CAS  Google Scholar 

  • Sommer, F. and Bäckhed, F. 2013. The gut microbiota-masters of host development and physiology. Nat. Rev. Microbiol. 11, 227–238.

    PubMed  CAS  Google Scholar 

  • Tedelind, S., Westberg, F., Kjerrulf, M., and Vidal, A. 2007. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World J. Gastroenterol. 13, 2826–2832.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Troll, J.V., Hamilton, M.K., Abel, M.L., Ganz, J., Bates, J.M., Stephens, W.Z., Melancon, E., van der Vaart, M., Meijer, A.H., Distel, M., et al. 2018. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling. Development 145, dev155317.

    PubMed  PubMed Central  Google Scholar 

  • Vannucci, F.A., Borges, E.L., de Oliveira, J.S.V., and Guedes, R.M.C. 2010. Intestinal absorption and histomorphometry of Syrian hamsters (Mesocricetus auratus) experimentally infected with Law-sonia intracellularis. Vet. Microbiol. 145, 286–291.

    PubMed  Google Scholar 

  • Vetrano, S., Rescigno, M., Cera, M.R., Correale, C., Rumio, C., Doni, A., Fantini, M., Sturm, A., Borroni, E., Repici, A., et al. 2008. Unique role of junctional adhesion molecule-a in maintaining mucosal homeostasis in inflammatory bowel disease. Gastroenterology 135, 173–184.

    PubMed  CAS  Google Scholar 

  • Wagner, M. and Horn, M. 2006. The Planctomycetes, Verrucomicrobia, Chlamydiae and sister phyla comprise a superphylum with biotechnological and medical relevance. Curr. Opin. Biotechnol. 17, 241–249.

    PubMed  CAS  Google Scholar 

  • Wang, X., Du, Y., and Liu, H. 2004. Preparation, characterization and antimicrobial activity of chitosanbAYZn complex. Carbohydr. Polym. 56, 21–26.

    CAS  Google Scholar 

  • Wang, J., Tian, S., Yu, H., Wang, J., and Zhu, W. 2019. Response of colonic mucosa-associated microbiota composition, mucosal immune homeostasis, and barrier function to early life galactooligosaccharides intervention in suckling piglets. J. Agric. Food Chem. 67, 578–588.

    PubMed  CAS  Google Scholar 

  • Wang, Y.H., Xu, M., Wang, F.N., Yu, Z.P., Yao, J.H., Zan, L.S., and Yang, F.X. 2010. Effect of dietary starch on rumen and small intestine morphology and digesta pH in goats. Livest. Sci. 122, 48–52.

    Google Scholar 

  • Xie, Z., Zhu, Y., Du, M., and Han, X. 2010. Effects of chitosan-zinc on growth performance, serum hormone and biochemical indices of weanling piglets. Chin. J. Anim. Nutr. 22, 1355–1360.

    CAS  Google Scholar 

  • Xu, Z.R., Hu, C.H., Xia, M.S., Zhan, X.A., and Wang, M.Q. 2003. Effects of dietary fructooligosaccharide on digestive enzyme activities, intestinal microflora and morphology of male broilers. Poult. Sci. 82, 1030–1036.

    PubMed  CAS  Google Scholar 

  • Yason, C.V. and Schat, K.A. 1987. Pathogenesis of rotavirus infection in various age groups of chickens and turkeys: clinical signs and virology. Am. J. Vet. Res. 48, 977–983.

    PubMed  CAS  Google Scholar 

  • Yin, H., Du, Y., and Zhang, J. 2009. Low molecular weight and oligomeric chitosans and their bioactivities. Curr. Top. Med. Chem. 9, 1546–1559.

    PubMed  CAS  Google Scholar 

  • Yu, M., Zhang, C., Yang, Y., Mu, C., Su, Y., Yu, K., and Zhu, W. 2017. Long-term effects of early antibiotic intervention on blood parameters, apparent nutrient digestibility, and fecal microbial fermentation profile in pigs with different dietary protein levels. J. Anim. Sci. Biotechnol. 8, 60.

    PubMed  PubMed Central  Google Scholar 

  • Zhang, C., Yu, M., Yang, Y., Mu, C., Su, Y., and Zhu, W. 2016. Effect of early antibiotic administration on cecal bacterial communities and their metabolic profiles in pigs fed diets with different protein levels. Anaerobe 42, 188–196.

    PubMed  Google Scholar 

  • Zheng, J., Xiao, X., Zhang, Q., Yu, M., Xu, J., Qi, C., and Wang, T. 2016. The effects of maternal and post-weaning diet interaction on glucose metabolism and gut microbiota in male mice offspring. Biosci. Rep. 36, e00341.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu, Y., Niu, Q., Shi, C., Wang, J., and Zhu, W. 2017. The role of microbiota in compensatory growth of protein-restricted rats. Microb. Biotechnol. 10, 480–491.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by National Key R&D Program of China (2017YFD0500505).

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  1. National Center for International Research on Animal Gut Nutrition, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, P. R. China

    Dan Feng, Minyang Zhang, Shiyi Tian, Jing Wang & Weiyun Zhu

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Correspondence to Jing Wang.

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Feng, D., Zhang, M., Tian, S. et al. Chitosan-chelated zinc modulates cecal microbiota and attenuates inflammatory response in weaned rats challenged with Escherichia coli. J Microbiol. 58, 780–792 (2020). https://doi.org/10.1007/s12275-020-0056-x

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