Online first
Review paper
Published online: 2023-09-29

open access

Page views 221
Article views/downloads 184
Get Citation

Connect on Social Media

Connect on Social Media

Potential role of microbiota in oncology and palliative care

Kornelia Pudło1, Zbigniew Żylicz1


Gut microbiota and intratumoural microbiota emerge as an important and, until now, completely ignored factor in treating cancer and cancer pain. Changes in gut microbiota can explain symptoms like the onset of cancer cachexia, inflammation, neuropathic pain and cancer pain. This knowledge offers perspectives of discovery of new therapeutic possibilities which may form a non-toxic complementary treatment of cancer with the potential of improving the quality of life of patients. This paper analyses current knowledge and future perspectives on this subject.

Article available in PDF format

View PDF Download PDF file


  1. Guo R, Chen LH, Xing Z, et al. Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential. Br J Anaesth. 2019; 123(5): 637–654.
  2. Santoni M, Miccini F, Battelli N. Gut microbiota, immunity and pain. Immunol Lett. 2021; 229: 44–47.
  3. Conlon MA, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014; 7(1): 17–44.
  4. Ley RE, Peterson AA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006; 124(4): 837–848.
  5. Hills Jr RD, Pontefract BA, Mishcon HR, et al. Gut microbiome: profound implications for diet and disease. Nutrients. 2019; 11(7): 1613.
  6. Egert M, de Graaf AA, Smidt H, et al. Beyond diversity: functional microbiomics of the human colon. Trends Microbiol. 2006; 14(2): 86–91.
  7. Rothschild D, Weissbrod O, Barkan E, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018; 555(7695): 210–215.
  8. Oleskin AV, Shenderov BA, Rogovsky VS. Role of neurochemicals in the interaction between the microbiota and the immune and the nervous system of the host organism. Probiotics Antimicrob Proteins. 2017; 9(3): 215–234.
  9. Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010; 330(6012): 1768–1773.
  10. Stewart E. Growing unculturable bacteria. J Bacteriol. 2012; 194(16): 4151–4160.
  11. Nguyen TL, Vieira-Silva S, Liston A, et al. How informative is the mouse for human gut microbiota research? Dis Model Mech. 2015; 8(1): 1–16.
  12. Mushegian AA, Ebert D. Rethinking “mutualism” in diverse host-symbiont communities. Bioessays. 2016; 38(1): 100–108.
  13. Morgan X, Segata N, Huttenhower C. Biodiversity and functional genomics in the human microbiome. Trends Genet. 2013; 29(1): 51–58.
  14. Viander B, Mäki M, Palva A. Impact of low salt concentration, salt quality on natural large-scale sauerkraut fermentation. Food Microbiol. 2003; 20(4): 391–395.
  15. Ranadheera S, Baines SK, Adams MC. Importance of food in probiotic efficacy. Food Res Int. 2010; 43(1): 1–7.
  16. Cammarota G, Ianiro G, Bibbò S, et al. Gut microbiota modulation: probiotics, antibiotics or fecal microbiota transplantation? Intern Emerg Med. 2014; 9(4): 365–373.
  17. Farkas J. Irradiation as a method for decontaminating food. A review. Int J Food Microbiol. 1998; 44(3): 189–204.
  18. Hu M, Miao M, Li K, et al. Human milk oligosaccharide lacto-N-tetraose: Physiological functions and synthesis methods. Carbohydr Polym. 2023; 316: 121067.
  19. Gunn D, Abbas Z, Harris HC, et al. Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies. Gut. 71; 5: 919–927.
  20. Kolida S, Gibson GR. Prebiotic capacity of inulin-type fructans. J Nutr. 2007; 137(11 Suppl): 2503S–2506S.
  21. Patangia DV, Ryan CA, Dempsey E, et al. Impact of antibiotics on the human microbiome and consequences for host health. Microbiologyopen. 2022; 11(1): 1260.
  22. Ma P, Mo R, Liao H, et al. Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice. J Neuroinflammation. 2022; 19(1): 169.
  23. Landy J, Al-Hassi HO, McLaughlin SD, et al. Review article: faecal transplantation therapy for gastrointestinal disease. Aliment Pharmacol Ther. 2011; 34(4): 409–415.
  24. Mattila E, Uusitalo–Seppälä R, Wuorela M, et al. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology. 2012; 142(3): 490–496.
  25. Mayer EA, Nance K, Chen S. The Gut-Brain Axis. Annu Rev Med. 2022; 73(1): 439–453.
  26. Martin CR, Osadchiy V, Kalani A, et al. The Brain-Gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol. 2018; 6(2): 133–148.
  27. Scher J, Abramson S. The microbiome and rheumatoid arthritis. Nat Rev Rheumatol. 2011; 7(10): 569–578.
  28. Kaetzel C. The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunol Rev. 2005; 206(1): 83–99.
  29. Viswanathan V, Hodges K, Hecht G. Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea. Nat Rev Microbiol. 2009; 7(2): 110–119.
  30. Mauro ADi, Neu J, Riezzo G, et al. Gastrointestinal function development and microbiota. Ital J Pediatr. 2013; 39(1).
  31. Burgueño J, Abreu M. Epithelial toll-like receptors and their role in gut homeostasis and disease. Nat Rev Gastroenterol Hepatol. 2020; 17(5): 263–278.
  32. Sansonetti PJ. War and peace at mucosal surfaces. Nat Rev Immunol. 2004; 4(12): 953–964.
  33. Kamdar K, Nguyen V, DePaolo RW. Toll-like receptor signaling and regulation of intestinal immunity. Virulence. 2013; 4(3): 207–212.
  34. Gierynska M, Szulc-Dabrowska L, Struzik J, et al. Integrity of the intestinal barrier: the involvement of epithelial cells and microbiota-a mutual relationship. Animals (Basel). 2022; 12(2): 145.
  35. Setiawan T, Sari IN, Wijaya YT, et al. Cancer cachexia: molecular mechanisms and treatment strategies. J Hematol Oncol. 2023; 16(1): 54.
  36. Zaorsky NG, Churilla TM, Egleston BL, et al. Causes of death among cancer patients. Annals Oncol. 2017; 28(2): 400–407.
  37. Solheim TS, Fearon KC, Blum D, et al. Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review. Acta Oncol. 2013; 52(1): 6–17.
  38. Solheim TS, Laird BJA, Balstad TR, et al. Cancer cachexia: rationale for the MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial. BMJ Supportive & Palliative Care. 2018; 8(3): 258–265.
  39. Herremans K, Riner A, Cameron M, et al. The microbiota and cancer cachexia. Int J Mol Sci. 2019; 20(24): 6267.
  40. van den Beuken-van Everdingen MH, Rijke JM, Kessels AG, et al. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007; 18(9): 1437–1449.
  41. Ji RR, Chamessian JA, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science. 2016; 354(6312): 572–577.
  42. Laird BJA, Scott AC, Colvin AL, et al. Cancer pain and its relationship to systemic inflammation: an exploratory study. Pain. 2011; 152(2): 460–463.
  43. Haywood A, Good P, Khan S, et al. Corticosteroids for the management of cancer-related pain in adults. Cochrane Database Syst Rev. 2015: CD010756.
  44. Li JS, Su SL, Xu Z, et al. Potential roles of gut microbiota and microbial metabolites in chronic inflammatory pain and the mechanisms of therapy drugs. Ther Adv Chronic Dis. 2022; 13.
  45. Wang F, Meng J, Znang L, et al. Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model. Sci Rep. 2018; 8(1): 3596.
  46. Lin B, Wang Y, Zhang P, et al. Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy. J Headache Pain. 2020; 21(1): 103.
  47. Miller RE, Ishihara S, Tran PB, et al. An aggrecan fragment drives osteoarthritis pain through Toll-like receptor 2. JCI Insight. 2018; 3(6): e95704.
  48. Das N, Dewan V, Grace P, et al. HMGB1 activates proinflammatory signaling via TLR5 leading to allodynia. Cell Rep. 2016; 17(4): 1128–1140.
  49. Amaral FA, Sachs D, Costa VV, et al. Commensal microbiota is fundamental for the development of inflammatory pain. Proc Natl Acad Sci USA. 2008; 105(6): 2193–2197.
  50. Gibson R, Keefe D. Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies. Support Care Cancer. 2006; 14(9): 890–900.
  51. Wardill H, Gibson R, Sebille YV, et al. Irinotecan-Induced gastrointestinal dysfunction and pain are mediated by common tlr4-dependent mechanisms. Mol Cancer Ther. 2016; 15(6): 1376–1386.
  52. Shen S, Lim G, You Z, et al. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017; 20(9): 1213–1216.
  53. Sheng J, Bora SH, Borchelt DR, et al. Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid beta peptide in APPswe transgenic mice. Neurobiol Dis. 2003; 14(1): 133–145.
  54. Bruno K, Woller S, Miller Y, et al. Targeting toll-like receptor-4 (TLR4)-an emerging therapeutic target for persistent pain states. Pain. 2018; 159(10): 1908–1915.
  55. Gabel F, Hovhannisyan V, Berkati AK, et al. Morphine-3-glucuronide, physiology and behavior. Front Mol Neurosci. 2022; 15: 882443.
  56. Christensen C, Jergensen L. Morphine-6-glucuronide has high affinity for the opioid receptor. Pharmacol Toxicol. 1987; 60(1): 75–76.
  57. Lötsch J, Geisslinger G. Morphine-6-glucuronide: an analgesic of the future? Clin Pharmacokinet. 2001; 40(7): 485–499.
  58. Kenyon EM, Calabrese EJ. Extent and implications of interspecies differences in the intestinal hydrolysis of certain glucuronide conjugates. Xenobiotica . 1993; 23(4): 373–381.
  59. Thomas KR, Watt J, Wu CMJ, et al. Pain and opioid-induced gut microbial dysbiosis. Biomedicines. 2022; 10(8): 1815.
  60. Zhang Li, Meng J, Ban Y, et al. Morphine tolerance is attenuated in germfree mice and reversed by probiotics, implicating the role of gut microbiome. Proc Natl Acad Sci USA. 2019; 116(27): 13523–13532.
  61. Deleemans JM, Chleilat F, Reimer RA, et al. The chemo-gut study: investigating the long-term effects of chemotherapy on gut microbiota, metabolic, immune, psychological and cognitive parameters in young adult cancer survivors; study protocol. BMC Cancer . 2019; 19(1): 1243.
  62. Enamorado M, Kulalert W, Han SJ, et al. Immunity to the microbiota promotes sensory neuron regeneration. Cell. 2023; 186(3): 607–620.e17.
  63. Lian N, Shen M, Zhang K, et al. Drinking hydrogen-rich water alleviates chemotherapy-induced neuropathic pain through the regulation of gut microbiota. J Pain Res. 2021; 14: 681–691.
  64. Chen P, Wan C, Ren YN, et al. Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain. Mol Brain. 2021; 1: 50.
  65. Pane K, Boccella S, Guida F, et al. Role of gut microbiota in neuropathy and neuropathic pain states: a systematic preclinical review. Neurobiol Dis. 2022; 170: 105773.
  66. Yao ZW, Yang X, Zhao BC, et al. Predictive and preventive potential of preoperative gut microbiota in chronic postoperative pain in breast cancer survivors. Anesth Analg. 2022; 134(4): 699–709.
  67. Kukkar A, Singh N, Jaggi A. Attenuation of neuropathic pain by sodium butyrate in an experimental model of chronic constriction injury in rats. J Formos Med Assoc. 2014; 113(12): 921–928.
  68. Heymann C, Bard JM, Heymann MF, et al. The intratumoral microbiome: Characterization methods and functional impact. Cancer Letters. 2021; 522: 63–79.
  69. Rodel F, Keilholz L, Herrmann M, et al. Radiobiological mechanisms in inflammatory diseases of low-dose radiation therapy. Int J Radiat Biol. 2007; 83(6): 357–366.
  70. Jiang Z, Zhang W, Zhang G, et al. Intratumoral microbiota: a new force in diagnosing and treating pancreatic cancer. Cancer Lett. 2023; 554: 216031.

Palliative Medicine in Practice