Skip to main content
Log in

Copper Changes Intestinal Microbiota of the Cecum and Rectum in Female Mice by 16S rRNA Gene Sequencing

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The aim of the present study was to investigate the effects of high concentrations of copper (Cu) on the cecum and rectum of intestinal microbiota in female mice. Twenty-four Kunming mice were weighed and randomly divided into two groups (n = 12 per group) including the control group and Cu group. Cu group was given drinking water with 5 mg/kg-bw copper chloride (CuCl2), while the control group was treated with drinking water without CuCl2. At the 90th day, results showed that compared with the control group, mice in the treatment group had a lower body weight, and the feces turned yellow and had a lower pH value. Histopathological lesions showed that the intestinal tissue from the treatment group had increased thickness of outer muscularis and smoothed muscle fiber, widened submucosa, decreased goblet cells, and showed blunting of intestinal villi and severe atrophy of central lacteal. In addition, at the genus level, 16S rRNA gene sequencing from the Cu group showed that Corynebacterium were significantly increased whereas Staphylococcaceae, Odoribacter, Rikenella, and Jeotgalicoccus were significantly decreased in the cecum. Dehalobacterium, Coprococcus, and Spirochaetales increased significantly whereas Salinicoccus, Bacillales, Staphylococcus, and Lactobacillales decreased sharply in the rectum. This study demonstrated that high concentrations of Cu could induce tissue injury and interrupt the homeostasis of microbiota.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Sun R, Chen L (2016) Assessment of heavy metal pollution in topsoil around Beijing metropolis. PLoS One 11:e155350

    Google Scholar 

  2. Lee IS, Kim OK, Chang YY, Bae B, Kim HH, Baek KH (2002) Heavy metal concentrations and enzyme activities in soil from a contaminated Korean shooting range. J Biosci Bioeng 94:406–411

    Article  CAS  Google Scholar 

  3. Papa S, Bartoli G, Pellegrino A, Fioretto A (2010) Microbial activities and trace element contents in an urban soil. Environ Monit Assess 165:193–203

    Article  CAS  Google Scholar 

  4. Sakhaee E, Emadi L, Azari O, Kheirandish R, Esmaili Nejad MR, Shafiei Bafti H (2016) Effects of Cuminum cyminum L. essential oil on some epididymal sperm parameters and histopathology of testes following experimentally induced copper poisoning in mice, vol 48, pp 542–547

    Google Scholar 

  5. Sakhaee E, Abshenas J, Emadi L, Azari O, Kheirandish R, Samaneh A (2014) Effects of vitamin C on epididymal sperm quality following experimentally induced copper poisoning in mice. Comp Clin Pathol 23:181–186

    Article  CAS  Google Scholar 

  6. O'Hara AM, Shanahan F (2006) The gut flora as a forgotten organ. EMBO Rep 7:688–693

    Article  CAS  Google Scholar 

  7. Kanno T, Matsuki T, Oka M, Utsunomiya H, Inada K, Magari H, Inoue I, Maekita T, Ueda K, Enomoto S, Iguchi M, Yanaoka K, Tamai H, Akimoto S, Nomoto K, Tanaka R, Ichinose M (2009) Gastric acid reduction leads to an alteration in lower intestinal microflora. Biochem Biophys Res Commun 381:666–670

    Article  CAS  Google Scholar 

  8. Arredondo M, Nunez MT (2005) Iron and copper metabolism. Mol Asp Med 26:313–327

    Article  CAS  Google Scholar 

  9. Ognik K, Stepniowska A, Cholewinska E, Kozlowski K (2016) The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium. Poult Sci 95:2045–2051

    Article  CAS  Google Scholar 

  10. Backhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 104:979–984

    Article  CAS  Google Scholar 

  11. Wang Z, Roberts AB, Buffa JA, Levison BS, Zhu W, Org E, Gu X, Huang Y, Zamanian-Daryoush M, Culley MK, DiDonato AJ, Fu X, Hazen JE, Krajcik D, DiDonato JA, Lusis AJ, Hazen SL (2015) Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163:1585–1595

    Article  CAS  Google Scholar 

  12. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J (2006) Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439:484–489

    Article  CAS  Google Scholar 

  13. Breton J, Massart S, Vandamme P, De Brandt E, Pot B, Foligne B (2013) Ecotoxicology inside the gut: impact of heavy metals on the mouse microbiome. BMC Pharmacol Toxicol 14:62

    Article  Google Scholar 

  14. Zhang J, Guo Z, Xue Z, Sun Z, Zhang M, Wang L, Wang G, Wang F, Xu J, Cao H, Xu H, Lv Q, Zhong Z, Chen Y, Qimuge S, Menghe B, Zheng Y, Zhao L, Chen W, Zhang H (2015) A phylo-functional core of gut microbiota in healthy young Chinese cohorts across lifestyles, geography and ethnicities. ISME J 9:1979–1990

    Article  Google Scholar 

  15. Mitra S, Keswani T, Ghosh N, Goswami S, Datta A, Das S, Maity S, Bhattacharyya A (2013) Copper induced immunotoxicity promote differential apoptotic pathways in spleen and thymus. Toxicology 306:74–84

    Article  CAS  Google Scholar 

  16. Zaura E, Keijser BJ, Huse SM, Crielaard W (2009) Defining the healthy “core microbiome” of oral microbial communities. BMC Microbiol 9:259

    Article  Google Scholar 

  17. Fan LM, Barry K, Hu GD, Meng SL, Song C, Wu W, Chen JZ, Xu P (2016) Bacterioplankton community analysis in tilapia ponds by Illumina high-throughput sequencing. World J Microbiol Biotechnol 32:10

  18. Zhao M, Du S, Li Q, Chen T, Qiu H, Wu Q, Chen S, Zhou Y, Zhang Y, Hu Y, Su Y, Shen L, Zhang F, Weng D, Li H (2017) High throughput 16SrRNA gene sequencing reveals the correlation between Propionibacterium acnes and sarcoidosis. Resp Res 18:28

  19. Bost M, Houdart S, Oberli M, Kalonji E, Huneau JO, Margaritis IN (2016) Dietary copper and human health: current evidence and unresolved issues. J Trace Elem Med Bio 35:107–115

    Article  CAS  Google Scholar 

  20. Su R, Wang R, Cao H, Pan J, Chen L, Li C, Shi D, Tang Z (2011) High copper levels promotes broiler hepatocyte mitochondrial permeability transition in vivo and in vitro. Biol Trace Elem Res 144:636–646

    Article  CAS  Google Scholar 

  21. Gaetke LM, Chow CK (2003) Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 189:147–163

    Article  CAS  Google Scholar 

  22. Kviatkovskaia IIa (1981) Effect of microbial preparations used in agriculture on the intestinal microflora. Gig Sanit (6):82–83

  23. Malinak CM, Hofacre CC, Collett SR, Shivaprasad HL, Williams SM, Sellers HS, Myers E, Wang YT, Franca M (2014) Tribasic copper chloride toxicosis in commercial broiler chicks. Avian Dis 58:642–649

    Article  Google Scholar 

  24. Schelder S, Zaade D, Litsanov B, Bott M, Brocker M (2011) The two-component signal transduction system CopRS of Corynebacterium glutamicum is required for adaptation to copper-excess stress. PLoS One 6:e22143

    Article  CAS  Google Scholar 

  25. Chang FJ, Coyne HJ, Cubillas C, Vinuesa P, Fang X, Ma Z, Ma D, Helmann JD, García-de Los Santos A, Wang Y, Dann CE, Giedroc DP (2014) Cu(I)-mediated allosteric switching in a copper-sensing operon repressor (CsoR). J Biol Chem 289:19204–19217

    Article  CAS  Google Scholar 

  26. Hussein EI, Jacob JH, Jahmani ASF, Yousef ND (2013) Dissemination of heavy metals and tolerant bacteria along Zarqa river (Jordan). J Biol Sci 13:100–111

    Article  CAS  Google Scholar 

  27. Leonard SS, Harris GK, Shi X (2004) Metal-induced oxidative stress and signal transduction. Free Radic Biol Med 37:1921–1942

    Article  CAS  Google Scholar 

  28. McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055

    CAS  PubMed  Google Scholar 

  29. Martins I, Goulart J, Martins E, Morales-Roman R, Marin S, Riou V, Colaco A, Bettencourt R (2017) Physiological impacts of acute cu exposure on deep-sea vent mussel Bathymodiolus azoricus under a deep-sea mining activity scenario. Aquat Toxicol 193:40–49

    Article  CAS  Google Scholar 

  30. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075

    Article  CAS  Google Scholar 

  31. Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint HJ (2000) Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol 66:1654–1661

    Article  CAS  Google Scholar 

  32. Fitzpatrick LR, Small JS, Greene WH, Karpa KD, Farmer S, Keller D (2012) Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-induced colitis following vancomycin withdrawal in mice. Gut Pathog 4:13

    Article  CAS  Google Scholar 

  33. Antharam VC, Li EC, Ishmael A, Sharma A, Mai V, Rand KH, Wang GP (2013) Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol 51:2884–2892

    Article  Google Scholar 

  34. Schwaiger K, Lzel CH, Mayer M, Bauer J: Notes on the almost unknown genus Jeotgalicoccus. Lett Appl Microbiol 50(4):441-4

  35. Meng X, Li S, Qin C, Zhu Z, Hu W, Yang L, Lu R, Li W, Nie G (2018) Intestinal microbiota and lipid metabolism responses in the common carp (Cyprinus carpio L.) following copper exposure. Ecotox Environ Safe 160:257–264

    Article  CAS  Google Scholar 

  36. Fang D, Yu Y, Wu L, Wang Y, Zhang J, Zhi J (2015) Bacillus subtilis-based colorimetric bioassay for acute biotoxicity assessment of heavy metal ions. RSC Adv 5:59472–59479

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This project was supported by the National Natural Science Foundation of China grant #31492266 awarded to PL, the Natural Science Foundation of Jiangxi Province grant #20171ACB21026 awarded to PL, the Technology R&D Program of Jiangxi Province grant #2014BBF60035 awarded to PL, and the Department of Education Science and Technology Research of Jiangxi Province grant # GJJ170243.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ping Liu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

All authors have read the manuscript and agreed to submit it in its current form for consideration for publication in the journal

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, S., Mao, H., Ruan, Y. et al. Copper Changes Intestinal Microbiota of the Cecum and Rectum in Female Mice by 16S rRNA Gene Sequencing. Biol Trace Elem Res 193, 445–455 (2020). https://doi.org/10.1007/s12011-019-01718-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-019-01718-2

Keywords

Navigation