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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Sep 26

PMID 26406888

Citations 71

Authors

Chun-Yan Yeung

Wai-Tao Chan

Chun-Bin Jiang

Mei-Lien Cheng

Chia-Yuan Liu

Szu-Wen Chang

Jen-Shiu Chiang Chiau

Hung-Chang Lee

Affiliations

Soon will be listed here.

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.

Citing Articles

Advancements in the Pathogenesis, Diagnosis, and Therapeutic Implications of Intestinal Bacteria.

Lu D, Ma X, Tao K, Lei H Curr Issues Mol Biol. 2025; 47(2).

PMID: 39996827 PMC: 11853859. DOI: 10.3390/cimb47020106.

Gut microbiota in cancer initiation, development and therapy.

Zhang R, Zhang X, Lau H, Yu J Sci China Life Sci. 2025; .

PMID: 39821827 DOI: 10.1007/s11427-024-2831-x.

Protective Effects of Cereal-Based Fermented Beverages Against 5-Fluorouracil-Induced Intestinal Damage in Mice.

Qin D, Fu W, Sun Y, Zhao L, Liu H, Fan D Nutrients. 2025; 16(24.

PMID: 39770954 PMC: 11679319. DOI: 10.3390/nu16244332.

Important Role of Intestinal Microbiota in Chemotherapy-induced Diarrhea and Therapeutics.

Jiang W, Wu Y, He X, Jiang L, Zhang W, Zheng W J Cancer. 2025; 16(2):648-659.

PMID: 39744484 PMC: 11685696. DOI: 10.7150/jca.99421.

Influence of Tryptophan Metabolism on the Protective Effect of Weissella paramesenteroides WpK4 in a Murine Model of Chemotherapy-Induced Intestinal Mucositis.

Guimaraes G, Costa K, da Silva Santana Moura C, Moreira S, Marchiori J, de Menezes Santos A Probiotics Antimicrob Proteins. 2024; .

PMID: 39602009 DOI: 10.1007/s12602-024-10413-1.

References

Wadler S, Benson 3rd A, Engelking C, Catalano R, Field M, Kornblau S . Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol. 1998; 16(9):3169-78. DOI: 10.1200/JCO.1998.16.9.3169. View

Rubenstein E, Peterson D, Schubert M, Keefe D, McGuire D, Epstein J . Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004; 100(9 Suppl):2026-46. DOI: 10.1002/cncr.20163. View

Haisan A, Rogojanu R, Croitoru C, Jitaru D, Tarniceriu C, Danciu M . Digital microscopy assessment of angiogenesis in different breast cancer compartments. Biomed Res Int. 2013; 2013:286902. PMC: 3773887. DOI: 10.1155/2013/286902. View

Bhatt V, Vendrell N, Nau K, Crumb D, Roy V . Implementation of a standardized protocol for prevention and management of oral mucositis in patients undergoing hematopoietic cell transplantation. J Oncol Pharm Pract. 2009; 16(3):195-204. DOI: 10.1177/1078155209348721. View

Wassenaar T, Klein G . Safety aspects and implications of regulation of probiotic bacteria in food and food supplements. J Food Prot. 2008; 71(8):1734-41. DOI: 10.4315/0362-028x-71.8.1734. View

Bellavia M, Rappa F, Lo Bello M, Brecchia G, Tomasello G, Leone A . Lactobacillus casei and bifidobacterium lactis supplementation reduces tissue damage of intestinal mucosa and liver after 2,4,6-trinitrobenzenesulfonic acid treatment in mice. J Biol Regul Homeost Agents. 2014; 28(2):251-61. View

Gibson R, Keefe D, Lalla R, Bateman E, Blijlevens N, Fijlstra M . Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer. 2012; 21(1):313-26. DOI: 10.1007/s00520-012-1644-z. View

Takiue S, Akiyoshi H . Light and scanning electron microscope examination of the digestive tract in peppered moray eel, Gymnothorax pictus (Elopomorpha). Anat Rec (Hoboken). 2013; 296(3):443-51. DOI: 10.1002/ar.22652. View

Keefe D, Schubert M, Elting L, Sonis S, Epstein J, Raber-Durlacher J . Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer. 2007; 109(5):820-31. DOI: 10.1002/cncr.22484. View

10.

Liong M . Safety of probiotics: translocation and infection. Nutr Rev. 2008; 66(4):192-202. DOI: 10.1111/j.1753-4887.2008.00024.x. View

11.

Maioli T, de Melo Silva B, Dias M, Paiva N, Nascimento Cardoso V, Fernandes S . Pretreatment with Saccharomyces boulardii does not prevent the experimental mucositis in Swiss mice. J Negat Results Biomed. 2014; 13:6. PMC: 4004512. DOI: 10.1186/1477-5751-13-6. View

12.

Galdeano C, Novotny Nunez I, de Moreno de LeBlanc A, Carmuega E, Weill R, Perdigon G . Impact of a probiotic fermented milk in the gut ecosystem and in the systemic immunity using a non-severe protein-energy-malnutrition model in mice. BMC Gastroenterol. 2011; 11:64. PMC: 3125276. DOI: 10.1186/1471-230X-11-64. View

13.

Tazuke Y, Maeda K, Wasa M, Satoko N, Fukuzawa M . Protective mechanism of glutamine on the expression of proliferating cell nuclear antigen after cisplatin-induced intestinal mucosal injury. Pediatr Surg Int. 2010; 27(2):151-8. DOI: 10.1007/s00383-010-2798-8. View

14.

Abimosleh S, Lindsay R, Butler R, Cummins A, Howarth G . Emu oil increases colonic crypt depth in a rat model of ulcerative colitis. Dig Dis Sci. 2011; 57(4):887-96. DOI: 10.1007/s10620-011-1979-1. View

15.

Benson 3rd A, Ajani J, Catalano R, Engelking C, Kornblau S, Martenson Jr J . Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004; 22(14):2918-26. DOI: 10.1200/JCO.2004.04.132. View

16.

Whitford E, Cummins A, Butler R, Prisciandaro L, Fauser J, Yazbeck R . Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent, 5-Fluorouracil (5-FU). Cancer Biol Ther. 2009; 8(6):505-11. View

17.

van Vliet M, Harmsen H, de Bont E, Tissing W . The role of intestinal microbiota in the development and severity of chemotherapy-induced mucositis. PLoS Pathog. 2010; 6(5):e1000879. PMC: 2877735. DOI: 10.1371/journal.ppat.1000879. View

18.

Fang H, Fang S, Chiang Chiau J, Yeung C, Chan W, Jiang C . Inhibitory effects of Lactobacillus casei subsp. rhamnosus on Salmonella lipopolysaccharide-induced inflammation and epithelial barrier dysfunction in a co-culture model using Caco-2/peripheral blood mononuclear cells. J Med Microbiol. 2010; 59(Pt 5):573-579. DOI: 10.1099/jmm.0.009662-0. View

19.

Carasi P, Diaz M, Racedo S, De Antoni G, Urdaci M, Serradell M . Safety characterization and antimicrobial properties of kefir-isolated Lactobacillus kefiri. Biomed Res Int. 2014; 2014:208974. PMC: 4052788. DOI: 10.1155/2014/208974. View

20.

Ewaschuk J, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J . Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol. 2008; 295(5):G1025-34. DOI: 10.1152/ajpgi.90227.2008. View