title: Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Yeung
authors.affiliation: Division of Gastroenterology and Nutrition, Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Wai-Tao
authors.initials: WT
authors.lastname: Chan
authors.affiliation: Division of Gastroenterology and Nutrition, Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chun-Bin
authors.initials: CB
authors.lastname: Jiang
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Mei-Lien
authors.initials: ML
authors.lastname: Cheng
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Hepatology and Gastroenterology, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chia-Yuan
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Division of Gastroenterology and Nutrition, Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Szu-Wen
authors.initials: SW
authors.lastname: Chang
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Jen-Shiu
authors.initials: JS
authors.lastname: Chiang Chiau
authors.affiliation: Division of Gastroenterology and Nutrition, Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, Taiwan; Department of Pediatrics, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hung-Chang
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001644:Bifidobacterium / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003967:Diarrhea / Q000178:diet therapy*; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007779:Lactobacillus acidophilus / Q000502:physiology; D007780:Lacticaseibacillus casei / Q000502:physiology; D051379:Mice; D052016:Mucositis / Q000097:blood / Q000139:chemically induced / Q000178:diet therapy*; D019936:Probiotics / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D005472:Fluorouracil