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PLoS One. 2015 Sep 25;10(9):e0138746. doi: 10.1371/journal.pone.0138746. eCollection 2015.

Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model.

Author information

1
Division of Gastroenterology and Nutrition, Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
2
Division of Gastroenterology and Nutrition, Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan.
3
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
4
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Hepatology and Gastroenterology, MacKay Memorial Hospital, Taipei, Taiwan.
5
Division of Gastroenterology and Nutrition, Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan; Department of Pediatrics, Taipei Medical University, Taipei, Taiwan.

Abstract

BACKGROUND AND AIMS:

Intestinal mucositis is a frequently encountered side effect in oncology patients undergoing chemotherapy. No well-established or up to date therapeutic strategies are available. To study a novel way to alleviate mucositis, we investigate the effects and safety of probiotic supplementation in ameliorating 5-FU-induced intestinal mucositis in a mouse model.

METHODS:

Seventy-two mice were injected saline or 5-Fluorouracil (5-FU) intraperitoneally daily. Mice were either orally administrated daily saline, probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35) or Lactobacillus acidophilus and Bifidobacterium bifidum (LaBi). Diarrhea score, pro-inflammatory cytokines serum levels, intestinal villus height and crypt depth and total RNA from tissue were assessed. Samples of blood, liver and spleen tissues were assessed for translocation.

RESULTS:

Marked diarrhea developed in the 5-FU groups but was attenuated after oral Lcr35 and LaBi administrations. Diarrhea scores decreased significantly from 2.64 to 1.45 and 0.80, respectively (P<0.001). Those mice in 5-FU groups had significantly higher proinflammatory cytokine levels (TNF-α: 234.80 vs. 29.10, P<0.001, IL-6: 25.13 vs. 7.43, P<0.001, IFN-γ: 22.07 vs. 17.06, P = 0.137). A repairing of damage in jejunal villi was observed following probiotics administration. We also found TNF-α, IL-1β and IL-6 mRNA expressions were up-regulated in intestinal mucositis tissues following 5-FU treatment (TNF-α: 4.35 vs. 1.18, IL-1β: 2.29 vs. 1.07, IL-6: 1.49 vs. 1.02) and that probiotics treatment suppressed this up-regulation (P<0.05). No bacterial translocation was found in this study.

CONCLUSIONS:

In conclusion, our results show that oral administration of probiotics Lcr35 and LaBi can ameliorate chemotherapy-induced intestinal mucositis in a mouse model. This suggests probiotics may serve as an alternative therapeutic strategy for the prevention or management of chemotherapy-induced mucositis in the future.

PMID:
26406888
PMCID:
PMC4583404
DOI:
10.1371/journal.pone.0138746
[Indexed for MEDLINE]
Free PMC Article

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