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Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy.

Publication ,  Journal Article
Perales-Puchalt, A; Perez-Sanz, J; Payne, KK; Svoronos, N; Allegrezza, MJ; Chaurio, RA; Anadon, C; Calmette, J; Biswas, S; Mine, JA; Nickels, L ...
Published in: J Leukoc Biol
May 2018

Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacerbate mucosal damage. Restoration of the microbiota through fecal-pellet gavage drives healing of cisplatin-induced intestinal damage. Bacterial translocation to the blood stream is correspondingly abrogated, resulting in a significant reduction in systemic inflammation, as evidenced by decreased serum IL-6 and reduced mobilization of granulocytes. Mechanistically, reversal of dysbiosis in response to fecal gavage results in the production of protective mucins and mobilization of CD11b+ myeloid cells to the intestinal mucosa, which promotes angiogenesis. Administration of Ruminococcus gnavus, a bacterial strain selectively depleted by cisplatin treatment, could only partially restore the integrity of the intestinal mucosa and reduce systemic inflammation, without measurable increases in the accumulation of mucin proteins. Together, our results indicate that reconstitution of the full repertoire of intestinal bacteria altered by cisplatin treatment accelerates healing of the intestinal epithelium and ameliorates systemic inflammation. Therefore, fecal microbiota transplant could paradoxically prevent life-threatening bacteremia in cancer patients treated with chemotherapy.

Duke Scholars

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Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

May 2018

Volume

103

Issue

5

Start / End Page

799 / 805

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Peritoneal Neoplasms
  • Ovarian Neoplasms
  • Intestines
  • Immunology
  • Gastrointestinal Microbiome
  • Female
  • Fecal Microbiota Transplantation
  • Dysbiosis
  • Cisplatin
 

Citation

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Chicago
ICMJE
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Perales-Puchalt, A., Perez-Sanz, J., Payne, K. K., Svoronos, N., Allegrezza, M. J., Chaurio, R. A., … Conejo-Garcia, J. R. (2018). Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy. J Leukoc Biol, 103(5), 799–805. https://doi.org/10.1002/JLB.5HI1117-446RR
Perales-Puchalt, Alfredo, Jairo Perez-Sanz, Kyle K. Payne, Nikolaos Svoronos, Michael J. Allegrezza, Ricardo A. Chaurio, Carmen Anadon, et al. “Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy.J Leukoc Biol 103, no. 5 (May 2018): 799–805. https://doi.org/10.1002/JLB.5HI1117-446RR.
Perales-Puchalt A, Perez-Sanz J, Payne KK, Svoronos N, Allegrezza MJ, Chaurio RA, et al. Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy. J Leukoc Biol. 2018 May;103(5):799–805.
Perales-Puchalt, Alfredo, et al. “Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy.J Leukoc Biol, vol. 103, no. 5, May 2018, pp. 799–805. Pubmed, doi:10.1002/JLB.5HI1117-446RR.
Perales-Puchalt A, Perez-Sanz J, Payne KK, Svoronos N, Allegrezza MJ, Chaurio RA, Anadon C, Calmette J, Biswas S, Mine JA, Costich TL, Nickels L, Wickramasinghe J, Rutkowski MR, Conejo-Garcia JR. Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy. J Leukoc Biol. 2018 May;103(5):799–805.

Published In

J Leukoc Biol

DOI

EISSN

1938-3673

Publication Date

May 2018

Volume

103

Issue

5

Start / End Page

799 / 805

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Peritoneal Neoplasms
  • Ovarian Neoplasms
  • Intestines
  • Immunology
  • Gastrointestinal Microbiome
  • Female
  • Fecal Microbiota Transplantation
  • Dysbiosis
  • Cisplatin