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The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity.

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  • معلومة اضافية
    • Author-Supplied Keywords:
      Anatomy
      Antibiotics
      Antimicrobials
      Biochemistry
      Biology and life sciences
      Colitis
      Colon
      Diagnostic medicine
      Digestive system
      DNA-binding proteins
      Drugs
      Gastroenterology and hepatology
      Gastrointestinal tract
      Gene expression
      Gene regulation
      Genetics
      Genomics
      Immune response
      Immunology
      Inflammation
      Inflammatory bowel disease
      Medical microbiology
      Medicine and health sciences
      Microbial control
      Microbial genomics
      Microbiology
      Microbiome
      Pathology and laboratory medicine
      Pharmacology
      Proteins
      Regulatory proteins
      Research Article
      Signs and symptoms
      Transcription factors
    • Abstract:
      Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E. coli, Clostridium, Staphylococcus spp. and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
    • Author Affiliations:
      1Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
      2UCLA/CURE West LA VA Medical Center, Los Angeles, California, United States of America
      3Bogomolets National Medical University, Kyiv, Ukraine
    • ISSN:
      1932-6203
    • Accession Number:
      10.1371/journal.pone.0220642
    • Accession Number:
      138192038
  • Citations
    • ABNT:
      HOLOTA, Y. et al. The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity. PLoS ONE, [s. l.], v. 14, n. 8, p. 1–25, 2019. DOI 10.1371/journal.pone.0220642. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=138192038&custid=s8280428. Acesso em: 20 out. 2020.
    • AMA:
      Holota Y, Dovbynchuk T, Kaji I, et al. The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity. PLoS ONE. 2019;14(8):1-25. doi:10.1371/journal.pone.0220642
    • APA:
      Holota, Y., Dovbynchuk, T., Kaji, I., Vareniuk, I., Dzyubenko, N., Chervinska, T., Zakordonets, L., Stetska, V., Ostapchenko, L., Serhiychuk, T., & Tolstanova, G. (2019). The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity. PLoS ONE, 14(8), 1–25. https://doi.org/10.1371/journal.pone.0220642
    • Chicago/Turabian: Author-Date:
      Holota, Yuliia, Taisa Dovbynchuk, Izumi Kaji, Igor Vareniuk, Natalia Dzyubenko, Tetiana Chervinska, Liudmyla Zakordonets, et al. 2019. “The Long-Term Consequences of Antibiotic Therapy: Role of Colonic Short-Chain Fatty Acids (SCFA) System and Intestinal Barrier Integrity.” PLoS ONE 14 (8): 1–25. doi:10.1371/journal.pone.0220642.
    • Harvard:
      Holota, Y. et al. (2019) ‘The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity’, PLoS ONE, 14(8), pp. 1–25. doi: 10.1371/journal.pone.0220642.
    • Harvard: Australian:
      Holota, Y, Dovbynchuk, T, Kaji, I, Vareniuk, I, Dzyubenko, N, Chervinska, T, Zakordonets, L, Stetska, V, Ostapchenko, L, Serhiychuk, T & Tolstanova, G 2019, ‘The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity’, PLoS ONE, vol. 14, no. 8, pp. 1–25, viewed 20 October 2020, .
    • MLA:
      Holota, Yuliia, et al. “The Long-Term Consequences of Antibiotic Therapy: Role of Colonic Short-Chain Fatty Acids (SCFA) System and Intestinal Barrier Integrity.” PLoS ONE, vol. 14, no. 8, Aug. 2019, pp. 1–25. EBSCOhost, doi:10.1371/journal.pone.0220642.
    • Chicago/Turabian: Humanities:
      Holota, Yuliia, Taisa Dovbynchuk, Izumi Kaji, Igor Vareniuk, Natalia Dzyubenko, Tetiana Chervinska, Liudmyla Zakordonets, et al. “The Long-Term Consequences of Antibiotic Therapy: Role of Colonic Short-Chain Fatty Acids (SCFA) System and Intestinal Barrier Integrity.” PLoS ONE 14, no. 8 (August 22, 2019): 1–25. doi:10.1371/journal.pone.0220642.
    • Vancouver/ICMJE:
      Holota Y, Dovbynchuk T, Kaji I, Vareniuk I, Dzyubenko N, Chervinska T, et al. The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity. PLoS ONE [Internet]. 2019 Aug 22 [cited 2020 Oct 20];14(8):1–25. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=asn&AN=138192038&custid=s8280428