Applied Biochemistry and Biotechnology

, Volume 172, Issue 8, pp 3810–3826 | Cite as

Impact of Targeted Specific Antibiotic Delivery for Gut Microbiota Modulation on High-Fructose-Fed Rats

  • Prasant Kumar Jena
  • Shilpa Singh
  • Bhumika Prajapati
  • G. Nareshkumar
  • Tejal Mehta
  • Sriram SeshadriEmail author


The objective of present investigation was to study the effect of gut microbiota alteration by oral administration of targeted delivery of pH sensitive cefdinir microspheres to high-fructose-fed (HFD) rats. Rats were fed with a high-fructose diet with or without cefdinir microsphere administration for 30 days. The fecal microbiota community, oral glucose tolerance, the markers of liver injury, plasma and hepatic lipids profile, and histological evaluation were investigated. The levels of blood glucose, liver injury markers, lipid profile in plasma and liver, and fat tissue were significantly increased in high-fructose-fed rats. However, after pH-sensitive cefdinir microsphere administration, the elevation of these parameters was significantly suppressed. Cef EL significantly lowered the increased AST (p < 0.05) and ALT (p < 0.001) levels in HFD group. There is a significant lower (p < 0.01) AUCglucose level in Cef EL group than HFD group The histological changes in the liver and the small and large intestines were more profound in HFD group as compared to cefdinir-treated HFD and control groups. Feeding of cefdinir microsphere sustained lactobacilli and bifidobacteria and significantly decreased (p < 0.05) the number of Enterobacteriaceae induced by HFD. Experimental evidences demonstrated that the effectiveness of pH-specific cefdinir microsphere on reducing insulin resistance and development of metabolic changes in high-fructose-fed rats and suggested that it may be a promising therapeutic agent in treating type 2 diabetes. Intestinal-targeted antibiotic delivery needs to be further explored for its therapeutic applications.


Cefdinir Microspheres Fructose Gut microbiota Diabetes Inflammation 



The authors are thankful to Nirma Education and Research Foundation (NERF), Ahmedabad for providing infrastructure and financial support. Authors are also thankful for the help and cooperation rendered by Dr. Sanjiv Acharya and Mr. Prerak Patel (Institute of Pharmacy, Nirma University).

Conflict of Interest

The authors declare that there are no conflicts of interest.

Supplementary material

12010_2014_772_MOESM1_ESM.docx (44 kb)
ESM 1 (DOCX 44 kb)


  1. 1.
    International Diabetes Federation. (2012). Diabetes atlas (5th ed.). Brussels: International Diabetes Federation.Google Scholar
  2. 2.
    Bayturan, O., Tuzcu, E. M., Lavoie, A., et al. (2010). The metabolic syndrome, its component risk factors, and progression of coronary atherosclerosis. Archives of Internal Medicine, 170(5), 478–484.CrossRefGoogle Scholar
  3. 3.
    Basciano, H., Federico, L., & Adeli, K. (2005). Fructose, insulin resistance, and metabolic dyslipidemia. Nutrition and Metabolism, 2(5), 1–14. doi: 10.1186/1743-7075-2-5.Google Scholar
  4. 4.
    Evans, J. L., Maddux, B. A., & Goldfine, I. D. (2005). The molecular basis for oxidative stress-induced insulin resistance. Antioxidant Redox Signal, 7(7–8), 1040–1052.CrossRefGoogle Scholar
  5. 5.
    Tuomilehto, J., Lindström, J., Eriksson, J. G., et al. (2001). Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New England Journal of Medicine, 344, 1343–1350.CrossRefGoogle Scholar
  6. 6.
    Willett, W., Manson, J., & Liu, S. (2001). Glycemic index, glycemic load, and risk of type 2 diabetes. American Journal of Clinical Nutrition, 76, 274S–280S.Google Scholar
  7. 7.
    Turnbaugh, P. J., Hamady, M., Yatsunenko, T., et al. (2009). A core gut microbiome in obese and lean twins. Nature, 457(7228), 480–484.CrossRefGoogle Scholar
  8. 8.
    Hildebrandt, M. A., Hoffmann, C., Sherrill-Mix, S. A., et al. (2009). High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology, 137(5), 1716–1724. e1711–1712.CrossRefGoogle Scholar
  9. 9.
    Dethlefsen, L., Huse, S., Sogin, M. L., & Relman, D. A. (2008). The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biology, 6(11), e280.CrossRefGoogle Scholar
  10. 10.
    Frank, D. N., St Amand, A. L., Feldman, R. A., et al. (2007). Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proceeding of National Academy of Science (PNAS), 104(34), 13780–13785.CrossRefGoogle Scholar
  11. 11.
    Duncan, S. H., Lobley, G. E., Holtrop, G., et al. (2008). Human colonic microbiota associated with diet, obesity and weight loss. International Journal of Obesity, 32(11), 1720–1724.CrossRefGoogle Scholar
  12. 12.
    Turnbaugh, P. J., Baeckhed, F., Fulton, L., & Gordon, J. I. (2008). Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host & Microbe, 3, 213–223.CrossRefGoogle Scholar
  13. 13.
    Murphy, E. F., Cotter, P. D., Healy, S., et al. (2010). Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut, 9, 1635–1642.CrossRefGoogle Scholar
  14. 14.
    Jernberg, C., Lofmark, S., Edlund, C., & Jansson, J. K. (2010). Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology, 156, 3216–3223.CrossRefGoogle Scholar
  15. 15.
    Shen, X., Yua, D., Zhua, L., et al. (2011). Electrospun diclofenac sodium loaded Eudragit L100-55 nanofibers for colon-targeted drug delivery. International Journal of Pharmaceutics, 408, 200–207.CrossRefGoogle Scholar
  16. 16.
    Gupta, V. K., Assmus, M. W., Beckert, T. E., & Price, J. C. (2001). A novel pH- and time-based multi-unit potential colonic drug delivery system. II. Optimization of multiple response variables. International Journal of Pharmaceutics, 213(1–2), 93–102.CrossRefGoogle Scholar
  17. 17.
    Maghsoodi, M., & Esfahani, M. (2009). Preparation of microparticles of naproxen with Eudragit RS and talc by spherical crystallization technique. Pharmaceutical Development Technology, 14(4), 442–450.CrossRefGoogle Scholar
  18. 18.
    Jain, D., Panda, A. K., & Majumdar, D. K. (2005). Eudragit S100 entrapped insulin microspheres for oral delivery. AAPS Pharmaceutical Science & Technology, 6(1), 100–107.CrossRefGoogle Scholar
  19. 19.
    Perry, C. M., & Scott, L. J. (2004). Cefdinir: a review of its use in the management of mild-to-moderate bacterial infections. Drugs, 64(13), 1433–1464.CrossRefGoogle Scholar
  20. 20.
    Basu, S. K., & Adhiyaman, R. (2008). Preparation and characterization of Nitrendipine-loaded Eudragit RL 100 microspheres prepared by an emulsion-solvent evaporation method. Tropical Journal of Pharmaceutical Research, 7(3), 1033–1041.CrossRefGoogle Scholar
  21. 21.
    Aleem, O., Kuchekar, B., Pore, Y., & Late, S. (2008). Effect of β-cyclodextrin and hydroxypropyl β-cyclodextrin complexation on physicochemical properties and antimicrobial activity of cefdinir. Journal of Pharmaceutical and Biomedical Analysis, 47, 535–540.CrossRefGoogle Scholar
  22. 22.
    Yadav, H., Jain, S., & Sinha, P. R. (2007). Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats. Nutrition, 23(1), 62–68.CrossRefGoogle Scholar
  23. 23.
    Xie, N., Cui, Y., Yin, Y. N., et al. (2011). Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet. BMC Complementary and Alternative Medicine, 11, 53.CrossRefGoogle Scholar
  24. 24.
    Park, J., Park, H. J., Cho, W., Cha, K. H., Kang, Y. S., & Hwang, S. J. (2010). Preparation and pharmaceutical characterization of amorphous cefdinir using spray-drying and SAS-process. International Journal of Pharmaceutics, 396, 239–245.CrossRefGoogle Scholar
  25. 25.
    Shanahan, F., & Murphy, E. (2011). The hybrid science of diet, microbes, and metabolic health. American Journal of Clinical Nutrition, 94(1), 1–2.CrossRefGoogle Scholar
  26. 26.
    Carvalho, B. M., Guadagnini, D., Tsukumo, D. M., et al. (2012). Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia, 55, 2823–2834.CrossRefGoogle Scholar
  27. 27.
    Membrez, M., Blancher, F., Jaquet, M., et al. (2008). Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice. FASEB Journal, 22(7), 2416–2426.CrossRefGoogle Scholar
  28. 28.
    Everson, S. A., Goldberg, D. E., Helmrich, S. P., Lakkam, T. A., et al. (1998). Weight gain and the risk of developing insulin resistance syndrome. Diabetes Care, 21, 1637–1643.CrossRefGoogle Scholar
  29. 29.
    Group DS. (1999). Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet, 354, 617–621.CrossRefGoogle Scholar
  30. 30.
    Polavarapu, R., Spitz, D. R., Sim, J. E., Follansbee, M. H., et al. (1998). Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology, 27, 1317–1323.CrossRefGoogle Scholar
  31. 31.
    Felig, P., Wahren, J., & Hendler, R. (1978). Influence of maturity-onset splanchnic glucose uptake in non–insulin-dependent diabetes mellitus diabetes on splanchnic glucose balance after oral glucose ingestion. Diabetes, 27, 121–126.CrossRefGoogle Scholar
  32. 32.
    Singh, V., & Chaudhary, A. K. (2011). Preparation of Eudragit E100 microspheres by modified solvent evaporation method. Acta Poloniae Pharmaceutica-Drug Research, 68(6), 975–980.Google Scholar
  33. 33.
    Trapani, A., Laquintana, V., Denora, N., Lopedota, A., Cutrignelli, A., & Franco, M. (2007). Eudragit RS 100 microparticles containing 2-hydroxypropyl-β-cyclodextrin and glutathione: physicochemical characterization, drug release and transport studies. European Journal of Pharmaceutical Sciences, 30, 64–74.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Prasant Kumar Jena
    • 1
  • Shilpa Singh
    • 1
  • Bhumika Prajapati
    • 1
  • G. Nareshkumar
    • 2
  • Tejal Mehta
    • 3
  • Sriram Seshadri
    • 1
    Email author
  1. 1.Institute of ScienceNirma UniversityAhmedabadIndia
  2. 2.Molecular Microbiology and Biochemistry Laboratory, Department of BiochemistryM. S. University of BarodaVadodaraIndia
  3. 3.Department of Pharmaceutics, Institute of PharmacyNirma UniversityAhmedabadIndia

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