Chemotherapy-induced modifications to gastrointestinal microflora: Evidence and implications of change

Current Drug Metabolism

Volumn 10, Issue 1, 2009, Pages 79-83

  Stringer, Andrea M ^a,b,d   Gibson, Rachel J ^a   Bowen, Joanne M ^a   Keefe, Dorothy M K ^a,b,c  

^a UNIVERSITY OF ADELAIDE   (Australia)

^b UNIVERSITY OF ADELAIDE   (Australia)

^c CANCER COUNCIL SOUTH AUSTRALIA   (Australia)

^d HANSON INSTITUTE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

7 ETHYL 10 HYDROXYCAMPTOTHECIN; ANTINEOPLASTIC AGENT; CAPECITABINE; CARBOPLATIN; CHLORAMBUCIL; FLUOROURACIL; IRINOTECAN; METHOTREXATE; PACLITAXEL; TOLL LIKE RECEPTOR;

ABDOMINAL PAIN; ANEMIA; BLOATING; BREAST CANCER; CANCER CHEMOTHERAPY; CLOSTRIDIUM DIFFICILE INFECTION; COLORECTAL CANCER; CONSTIPATION; DERMATITIS; DIARRHEA; DIGESTIVE SYSTEM FUNCTION DISORDER; DOSE LIVER FUNCTION RELATION; DRUG DETERMINATION; DRUG EXCRETION; DRUG METABOLISM; FATIGUE; FECES MICROFLORA; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; GENE EXPRESSION; HAND FOOT SYNDROME; HEARTBURN; HEMATOLOGIC MALIGNANCY; HUMAN; HYPERBILIRUBINEMIA; INFECTIOUS DIARRHEA; INTESTINE FLORA; LARGE INTESTINE MICROFLORA; LEUKOPENIA; LIVER ABSCESS; LIVER CANCER; LYMPHOCYTOPENIA; MICROFLORA; MUCOSA INFLAMMATION; NAUSEA; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; SMALL INTESTINE MICROFLORA; SOLID TUMOR; STOMACH MICROFLORA; THROMBOCYTOPENIA; UPREGULATION; VOMITING; ANIMAL; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; GASTROINTESTINAL TRACT; INTESTINE MUCOSA; LARGE INTESTINE; MICROBIOLOGY; PATHOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; DIARRHEA; GASTROINTESTINAL TRACT; HUMANS; INTESTINAL MUCOSA; INTESTINE, LARGE; MUCOSITIS;

EID: 62749156495     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920009787048419     Document Type: Review

References (71)

1. Cunningham, D.; Morgan, R.J.; Mills, P.R.; Nelson, L.M.; Toner, P.G.; Soukop, M.; McArdle, C.S. Russell, R.I. Functional and structural changes of the human proximal small intestine after cytotoxic therapy. J. Clin. Pathol., 1985, 38(3), 265-270.
2. Keefe, D.M. Gastrointestinal mucositis: a new biological model. Support Care Cancer, 2004, 12(1), 6-9.
3. Keefe, D.M.; Brealey, J.; Goland, G.J. Cummins, A.G. Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans. Gut, 2000, 47(5), 632-637.
4. Keefe, D.M.; Cummins, A.G.; Dale, B.M.; Kotasek, D.; Robb, T.A. Sage, R.E. Effect of high-dose chemotherapy on intestinal permeability in humans. Clin. Sci. (Lond.), 1997, 92(4), 385-389.
5. Mitchell, E.P. Schein, P.S. Gastrointestinal toxicity of chemotherapeutic agents. Toxic. Chemother., 1984, 269-285.
6. Sonis, S.T. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol., 1998, 34(1), 39-43.
7. Sonis, S.T. A biological approach to mucositis. J. Support Oncol., 2004, 2(1), 21-32, discussion 35-26.
8. Sonis, S.T. The pathobiology of mucositis. Nat. Rev. Cancer, 2004, 4(4), 277-284.
9. Bowen, J.M.; Gibson, R.J.; Keefe, D.M. Cummins, A.G. Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small intestine of rats and humans. Pathology, 2005, 37(1), 56-62.
10. Gibson, R.J.; Bowen, J.M.; Inglis, M.R.; Cummins, A.G. Keefe, D.M. Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer.J. Gastroenterol. Hepatol., 2003, 18(9), 1095-1100.
11. Gibson, R.J.; Keefe, D.M.; Clarke, J.M.; Regester, G.O.; Thompson, F.M.; Goland, G.J.; Edwards, B.G. Cummins, A.G. The effect of keratinocyte growth factor on tumour growth and small intestinal mucositis after chemotherapy in the rat with breast cancer. Cancer Chemother. Pharmacol., 2002, 50(1), 53-58.
12. Keefe, D.M.; Gibson, R.J. Hauer-Jensen, M. Gastrointestinal mucositis. Semin. Oncol. Nurs., 2004, 20(1), 38-47.
13. Sadler, T. Langman's Medical Embryology, Philadelphia: Lippincott Williams & Wilkins, 2006.
14. Burkitt, H.; Young, B.; Heath, J. Wheater's Functional Histology; A Text and Colour Atlas., London: Churchill Livingstone. 1993, 247-270.
15. Junqueira, L.; Carneiro, J.; Kelley, R. Basic Histology. Stamford, Connecticut: Appleton & Lange 1995, 281-300.
16. Gibson, R.J.; Keefe, D.M. Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies. Support Care Cancer, 2006, 14(9), 890-900.
17. Chandrasoma, P.; Taylor, C. Concise Pathology. Stamford, Connicticut: Appleton & Lange 1998, 571-599.
18. Sherwood, L. Human Physiology: From Cells to Systems. United States of America: Wadsworth Publishing Company 1997, 584-594.
19. Simon, G.L.; Gorbach, S.L. Intestinal microflora. Med. Clin. North Am., 1982, 66(3), 557-574.
20. Evaldson, G.; Heimdahl, A.; Kager, L. Nord, C.E. The normal human anaerobic microflora. Scand J. Infect. Dis. Suppl., 1982, 35,9-15.
21. Heller, F.; Duchmann, R. Intestinal flora and mucosal immune responses. Int. J. Med. Microbiol., 2003, 293(1), 77-86.
22. Gorbach, S.L. Intestinal microflora. Gastroenterology, 1971, 60(6), 1110-1129.
23. Gustafsson, B.E. The physiological importance of the colonic microflora. Scand. J. Gastroenterol. Suppl., 1982, 77, 117-131.
24. Umesaki, Y.; Okada, Y.; Imaoka, A.; Setoyama, H. Matsumoto, S. Interactions between epithelial cells and bacteria, normal and pathogenic. Science, 1997, 276(5314), 964-965.
25. Dai, D.; Walker, W.A. Protective nutrients and bacterial colonization in the immature human gut. Adv. Pediatr., 1999, 46, 353-382.
26. Rhee, K.J.; Sethupathi, P.; Driks, A.; Lanning, D.K. Knight, K.L. Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J. Immunol., 2004, 172(2), 1118-1124.
27. Lee, J.; Mo, J.H.; Katakura, K.; Alkalay, I.; Rucker, A.N.; Liu, Y.T.; Lee, H.K.; Shen, C.; Cojocaru, G.; Shenouda, S.; Kagnoff, M.; Eckmann, L.; Ben-Neriah, Y.; Raz, E. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat. Cell Biol., 2006, 8(12), 1327-1336.
28. Lee, J.; Mo, J.H.; Shen, C.; Rucker, A.N.; Raz, E. Toll-like receptor signaling in intestinal epithelial cells contributes to colonic homoeostasis. Curr. Opin. Gastroenterol., 2007, 23(1), 27-31.
29. Umesaki, Y.; Setoyama, H. Structure of the intestinal flora responsible for development of the gut immune system in a rodent model. Microbes Infect., 2000, 2(11), 1343-1351.
30. Simon, G.L.; Gorbach, S.L. Intestinal flora in health and disease. Gastroenterology, 1984, 86(1), 174-193.
31. Simon, G.L.; Gorbach, S.L. The human intestinal microflora. Dig. Dis. Sci., 1986, 31(9 Suppl), 147S-162S.
32. Stringer, A.M.; Gibson, R.J.; Logan, R.M.; Bowen, J.M.; Yeoh, A.S.; Burns, J.; Keefe, D.M. Chemotherapy-induced diarrhea is associated with changes in the luminal environment in the DA rat. Exp. Biol. Med., (Maywood) 2007, 232(1), 96-106.
33. Matsuki, T.; Watanabe, K.; Fujimoto, J.; Takada, T.; Tanaka, R. Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces. Appl. Environ. Microbiol., 2004, 70(12), 7220-7228.
34. De Vita V. Jr. in Cancer: Principles and Practice of Oncology, De Vita V. Jr. Ed. Lippincott-Raven: Philadelphia 1997, 333-347.
35. Duncan, M.; Grant, G. Oral and intestinal mucositis - causes and possible treatments. Aliment Pharmacol. Ther., 2003, 18(9), 853-874.
36. Ikuno, N.; Soda, H.; Watanabe, M.; Oka, M. Irinotecan (CPT-11) and characteristic mucosal changes in the mouse ileum and cecum. J. Natl. Cancer Inst., 1995, 87(24), 1876-1883.
37. Takasuna, K.; Hagiwara, T.; Hirohashi, M.; Kato, M.; Nomura, M.; Nagai, E.; Yokoi, T.; Kamataki, T. Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res., 1996, 56(16), 3752-3757.
38. Gibson, R.J.; Keefe, D.M.; Thompson, F.M.; Clarke, J.M.; Goland, G.J.; Cummins, A.G. Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats. Dig. Dis. Sci., 2002, 47(12), 2751-2757.
39. Alimonti, A.; Gelibter, A.; Pavese, I.; Satta, F.; Cognetti, F.; Ferretti, G.; Rasio, D.; Vecchione, A.; Di Palma, M. New approaches to prevent intestinal toxicity of irinotecan-based regimens. Cancer Treat Rev., 2004, 30(6), 555-562.
40. Araki, E.; Ishikawa, M.; Iigo, M.; Koide, T.; Itabashi, M.; Hoshi, A. Relationship between development of diarrhea and the concentration of SN-38, an active metabolite of CPT-11, in the intestine and the blood plasma of athymic mice following intraperitoneal administration of CPT-11. Jpn. J. Cancer Res., 1993, 84(6), 697-702.
41. Cao, S.; Black, J.D.; Troutt, A.B.; Rustum, Y.M. Interleukin 15 offers selective protection from irinotecan-induced intestinal toxicity in a preclinical animal model. Cancer Res., 1998, 58(15), 3270-3274.
42. Ma, M.K.; McLeod, H.L. Lessons learned from the irinotecan metabolic pathway. Curr. Med. Chem., 2003, 10, 41-49.
43. Takasuna, K.; Hagiwara, T.; Watanabe, K.; Onose, S.; Yoshida, S.; Kumazawa, E.; Nagai, E. Kamataki, T. Optimal antidiarrhea treatment for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea. Cancer Chemother. Pharmacol., 2006, 58(4), 494-503.
44. Fittkau, M.; Voigt, W.; Holzhausen, H.J.; Schmoll, H.J. Saccharic acid 1. 4-lactone protects against CPT-11-induced mucosa damage in rats. J. Cancer Res. Clin. Oncol., 2004, 130(7), 388-394.
45. Gibson, R.J.; Bowen, J.M.; Keefe, D.M. Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor-bearing DA rats. Int. J. Cancer, 2005, 116(3), 464-470.
46. Gibson, R.J.; Stringer, A.M.; Bowen, J.M.; Logan, R.M.; Yeoh, A.S.; Burns, J.; Alvarez, E.; Keefe, D.M. Velafermin improves gastrointestinal mucositis following irinotecan treatment in tumor-bearing DA rats. Cancer Biol. Ther., 2007, 6(4), 541-547.
47. Takasuna, K.; Hagiwara, T.; Hirohashi, M.; Kato, M.; Nomura, M.; Nagai, E.; Yokoi, T. Kamataki, T. Inhibition of intestinal microflora beta-glucuronidase modifies the distribution of the active metabolite of the antitumor agent, irinotecan hydrochloride (CPT-11) in rats. Cancer Chemother. Pharmacol., 1998, 42(4), 280-286.
48. Stringer, A.; Gibson, R.; Logan, R.; Bowen, J.; Yeoh, A.; Keefe, D. Faecal microflora and β-glucuronidase expression are altered in an irinotecan-induced diarrhoea model in rats. Cancer Biol. Ther., 2008, 7(12).
49. Bowen, J.M.; Gibson, R.J.; Cummins, A.G.; Tyskin, A.; Keefe, D.M. Irinotecan changes gene expression in the small intestine of the rat with breast cancer. Cancer Chemother. Pharmacol., 2007, 59(3), 337-348.
50. Bowen, J.M.; Gibson, R.J.; Tsykin, A.; Stringer, A.M.; Logan, R.M.; Keefe, D.M. Gene expression analysis of multiple gastrointestinal regions reveals activation of common cell regulatory pathways following cytotoxic chemotherapy. Int. J. Cancer, 2007, 121(8), 1847-1856.
51. Gutheil, J.C.; Kearns, C.M. in The Chemotherapy Source Book, Perry, M.C. Ed., Williams and Wilkins: Baltimore 1997, 317-344.
52. Macdonald, D.R., in The Chemotherapy Source Book, M.C. Perry, Ed. Williams and Wilkins: Baltimore. 1997, 745-766.
53. Von Bultzingslowen, I.; Adlerberth, I.; Wold, A.E.; Dahlen, G.; Jontell, M. Oral and intestinal microflora in 5-fluorouracil treated rats, translocation to cervical and mesenteric lymph nodes and effects of probiotic bacteria. Oral Microbiol. Immunol., 2003, 18(5), 278-284.
54. Berg, D.T. Capecitabine: a new adjuvant option for colorectal cancer. Clin. J. Oncol. Nurs., 2006, 10(4), 479-486.
55. Hoff, P.M.; Ansari, R.; Batist, G.; Cox, J.; Kocha, W.; Kuperminc, M.; Maroun, J.; Walde, D.; Weaver, C.; Harrison, E.; Burger, H.U.; Osterwalder, B.; Wong, A.O.; Wong, R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J. Clin. Oncol., 2001, 19(8), 2282-2292.
56. Van Cutsem, E.; Twelves, C.; Cassidy, J.; Allman, D.; Bajetta, E.; Boyer, M.; Bugat, R.; Findlay, M.; Frings, S.; Jahn, M.; McKendrick, J.; Osterwalder, B.; Perez-Manga, G.; Rosso, R.; Rougier, P.; Schmiegel, W.H.; Seitz, J.F.; Thompson, P.; Vieitez, J.M.; Weitzel, C.; Harper, P. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J. Clin. Oncol., 2001, 19(21), 4097-4106.
57. Lieuw-a-Fa, M.; Peringa, J.; Leeksma, O.; Terpstra, W. Sepsis from liver abscesses in metastatic colorectal carcinoma after chemoimmunotherapy. J. Clin. Oncol., 2008, 26(8), 1381-1382.
58. Achord, J.L. The effect of methotrexate on rabbit intestinal mucosal enzymes and flora. Am. J. Dig. Dis., 1969, 14(5), 315-323.
59. Ramos, A.; Martinez-Taboada, V.M.; Fito, C.; Rodriguez-Valverde, V. Clostridium difficile-associated diarrhea in rheumatoid arthritis patients who are receiving therapy with low-dose chlorambucil. Arthritis Rheum., 1997, 40(11), 2090-2091.
60. Gifford, A.H.; Kirkland, K.B. Risk factors for Clostridium difficile-associated diarrhea on an adult hematology-oncology ward. Eur. J. Clin. Microbiol. Infect. Dis., 2006, 25(12), 751-755.
61. Yamazawa, K.; Kanno, H.; Seki, K.; Kuzuta, T.; Matsui, H.; Sekiya, S. Life-threatening Clostridium difficile-associated diarrhea induced by paclitaxel-carboplatin combination chemotherapy. Acta Obstet. Gynecol. Scand., 2001, 80(8), 768-769.
62. Husain, A.; Aptaker, L.; Spriggs, D.R.; Barakat, R.R. Gastrointestinal toxicity and Clostridium difficile diarrhea in patients treated with paclitaxel-containing chemotherapy regimens. Gynecol. Oncol., 1998, 71(1), 104-107.
63. Kamthan, A.G.; Bruckner, H.W.; Hirschman, S.Z.; Agus, S.G. Clostridium difficile diarrhea induced by cancer chemotherapy. Arch. Intern. Med., 1992, 152(8), 1715-1717.
64. Bodet, C.A., 3rd; Jorgensen, J.H.; Drutz, D.J. Antibacterial activities of antineoplastic agents. Antimicrob. Agents Chemother., 1985, 28(3), 437-439.
65. Gosselink, M.P.; Schouten, W.R.; van Lieshout, L.M.; Hop, W.C.; Laman, J.D.; Ruseler-van Embden, J.G. Eradication of pathogenic bacteria and restoration of normal pouch flora: comparison of metronidazole and ciprofloxacin in the treatment of pouchitis. Dis. Colon Rectum, 2004, 47(9), 1519-1525.
66. Haenel, H. Human normal and abnormal gastrointestinal flora. Am. J. Clin. Nutr., 1970, 23(11), 1433-1439.
67. Klainer, A.S.; Gorbach, S.; Weinstein, L. Studies of intestinal microflora. VI. Effect of x irradiation on the fecal microflora of the rat. J. Bacteriol., 1967, 94(2), 378-382.
68. Klainer, A.S.; Gorbach, S. Weinstein, L. Studies of intestinal microflora. VII. Effect of diet and fecal microbial flora on survival of animals exposed to x irradiation. J. Bacteriol., 1967, 94(2), 383-387.
69. Kofteridis, D.P.; Maraki, S.; Mixaki, I.; Mantadakis, E. Samonis, G. Impact of prolonged treatment with trimethoprim-sulfamethoxazole on the human gut flora. Scand. J. Infect. Dis., 2004, 36(10), 771-772.
70. Si, J.M.; Yu, Y.C.; Fan, Y.J.; Chen, S.J. Intestinal microecology and quality of life in irritable bowel syndrome patients. World J. Gastroenterol., 2004, 10(12), 1802-1805.
71. Anthony, L.; Bowen, J.; Garden, A.; Hewson, I.; Sonis, S. New thoughts on the pathobiology of regimen-related mucosal injury. Support Care Cancer, 2006, 14(6), 516-518.