Skip to main content

Advertisement

Springer Nature Link
Log in

Exploring the links among inflammation and gut microbiome with psychoneurological symptoms and gastrointestinal toxicities in gynecologic cancers: a systematic review

  • Review Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Introduction

Emerging evidence highlights the roles the gut microbiome and the immune system, integral parts of the gut-brain axis, play in developing various symptoms in cancer patients. The purpose of this systematic review was to describe the roles of inflammatory markers and the gut microbiome, as well as to describe their associations with psychoneurological symptoms and gastrointestinal toxicities in women with gynecologic cancers.

Methods

A comprehensive literature search was conducted in PubMed, Embase, and Web of Science from January 2000 to February 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were utilized to screen the found articles. The quality of the included studies was assessed using the Mixed Method Assessment Tool. In the included studies, various inflammatory markers and gut microbiome diversity and patterns were measured.

Results

Sixteen studies met the eligibility criteria and were included in this systematic review. While there were discrepancies in the associations between various inflammatory markers and symptoms, most of the studies showed positive correlations between interleukin‐6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and cancer-related psychoneurological symptoms and gastrointestinal toxicities in gynecologic cancer patients. Although there was no consensus in alpha diversity, studies showed significant dissimilarity in the microbial communities (beta diversity) in patients with gastrointestinal toxicities compared with patients without symptoms or healthy controls. Studies also reported inconsistent findings in the abundance of bacteria at different taxonomic levels. Radiation enteritis-derived microbiota could stimulate TNF-α and interleukin 1 beta (IL-1β) secretion.

Conclusions

Alteration of inflammatory markers, the gut microbiome, and their associations show emerging evidence in the development of psychoneurological symptoms and gastrointestinal toxicities in women with gynecologic cancers. More studies on the interactions between the immune system and the gut microbiome, two integral parts of the gut-brain axis, are required to shed light on the roles they play in symptom development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
€34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

Availability of data and material

Not applicable.

Code availability

Not applicable.

References

  1. and_Prevention, C.f.D.C. (2021) Gynecologic cancers. Available from: https://www.cdc.gov/cancer/gynecologic/basic_info/what-is-gynecologic-cancer.htm

  2. Institute, N.C. (2020) Cancer statistics. Available from: https://seer.cancer.gov/statfacts/html/cervix.html

  3. Cancer.Net. (2020) Uterine cancer: statistics. 9. Available from: https://www.cancer.net/cancer-types/uterine-cancer/statistics.

  4. Lopez-Fernandez T et al (2019) Atrial fibrillation in active cancer patients: expert position paper and recommendations. Revista Española de Cardiología (English Edition) 72(9):749–759

    Article  Google Scholar 

  5. Wu J et al (2018) Improved survival in ovarian cancer, with widening survival gaps of races and socioeconomic status: a period analysis, 1983–2012. J Cancer 9(19):3548

    Article  PubMed  PubMed Central  Google Scholar 

  6. Poort H et al (2020) Patterns and predictors of cancer-related fatigue in ovarian and endometrial cancers: 1-year longitudinal study. Cancer 126(15):3526–3533

    Article  CAS  PubMed  Google Scholar 

  7. Miaskowski C et al (2017) Advancing symptom science through symptom cluster research: expert panel proceedings and recommendations. JNCI J Natl Cancer Inst 109(4)

  8. Paice JA. Pain management in gynecologic cancer

  9. Bai J et al (2021) Gut microbiome and its associations with acute and chronic gastrointestinal toxicities in cancer patients with pelvic radiation therapy: a systematic review. Front Oncol 5237

  10. Viswanathan AN et al (2014) Complications of pelvic radiation in patients treated for gynecologic malignancies. Cancer 120(24):3870–3883

    Article  PubMed  Google Scholar 

  11. Palesh OG et al (2010) Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: University of Rochester Cancer Center-Community Clinical Oncology Program. J Clin Oncol 28(2):292–298

    Article  PubMed  Google Scholar 

  12. Linden W et al (2012) Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord 141(2–3):343–351

    Article  PubMed  Google Scholar 

  13. Chan Y et al (2001) A longitudinal study on quality of life after gynecologic cancer treatment. Gynecol Oncol 83(1):10–19

    Article  CAS  PubMed  Google Scholar 

  14. Miller D, Nevadunsky N (2018) Palliative care and symptom management for women with advanced ovarian cancer. Hematol Oncol Clin 32(6):1087–1102

    Article  Google Scholar 

  15. Society, A.C. (2019) Cancer treatment & survivorship facts & figures 2019–2021. American Cancer Society Atlanta, GA

  16. Casey C, Chen L-M, Rabow MW (2011) Symptom management in gynecologic malignancies. Expert Rev Anticancer Ther 11(7):1079–1091

    Article  Google Scholar 

  17. Majeed H, Gupta V (2020) Adverse effects of radiation therapy. StatPearls [Internet]

  18. Nho J-H, Kim SR, Nam J-H (2017) Symptom clustering and quality of life in patients with ovarian cancer undergoing chemotherapy. Eur J Oncol Nurs 30:8–14

    Article  PubMed  Google Scholar 

  19. Beesley VL et al (2020) When will I feel normal again? Trajectories and predictors of persistent symptoms and poor wellbeing after primary chemotherapy for ovarian cancer. Gynecol Oncol 159(1):179–186

    Article  PubMed  Google Scholar 

  20. Honerlaw KR et al (2016) Biopsychosocial predictors of pain among women recovering from surgery for endometrial cancer. Gynecol Oncol 140(2):301–306

    Article  PubMed  Google Scholar 

  21. Ahlberg K, Ekman T, Gaston-Johansson F (2004) Levels of fatigue compared to levels of cytokines and hemoglobin during pelvic radiotherapy: a pilot study. Biol Res Nurs 5(3):203–210

    Article  PubMed  Google Scholar 

  22. Dantzer R et al (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Quan N (2014) In-depth conversation: spectrum and kinetics of neuroimmune afferent pathways. Brain Behav Immun 40:1–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Duffy SA et al (2013) Health behaviors predict higher interleukin-6 levels among patients newly diagnosed with head and neck squamous cell carcinoma. Cancer Epidemiol Prev Biomarkers 22(3):374–381

    Article  CAS  Google Scholar 

  25. Xiao C et al (2016) Fatigue is associated with inflammation in patients with head and neck cancer before and after intensity-modulated radiation therapy. Brain Behav Immunol 52:145–152

    Article  Google Scholar 

  26. Clevenger L et al (2012) Sleep disturbance, cytokines, and fatigue in women with ovarian cancer. Brain Behav Immunol 26(7):1037–1044

    Article  Google Scholar 

  27. Tucker JA et al (2021) Longitudinal changes in sleep: associations with shifts in circulating cytokines and emotional distress in a cancer survivor population. Int J Behav Med 28(1):140–150

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lutgendorf SK et al (2008) Depressed and anxious mood and T-cell cytokine expressing populations in ovarian cancer patients. Brain Behav Immunol 22(6):890–900

    Article  CAS  Google Scholar 

  29. Lutgendorf SK et al (2008) Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma. Clin Cancer Res 14(21):6839–6846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang Z et al (2019) Gut microbial dysbiosis is associated with development and progression of radiation enteritis during pelvic radiotherapy. J Cell Mol Med 23(5):3747–3756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee CS, Ryan EJ, Doherty GA (2014) Gastro-intestinal toxicity of chemotherapeutics in colorectal cancer: the role of inflammation. World J Gastroenterol WJG 20(14):3751

    Article  PubMed  CAS  Google Scholar 

  32. Bai J et al (2020) Gut microbiome associated with the psychoneurological symptom cluster in patients with head and neck cancers. Cancers 12(9):2531

    Article  CAS  PubMed Central  Google Scholar 

  33. Paulsen JA et al (2017) Gut microbiota composition associated with alterations in cardiorespiratory fitness and psychosocial outcomes among breast cancer survivors. Support Care Cancer 25(5):1563–1570

    Article  PubMed  PubMed Central  Google Scholar 

  34. González-Mercado VJ et al (2021) Changes in gut microbiome associated with co-occurring symptoms development during chemo-radiation for rectal cancer: a proof of concept study. Biol Res Nurs 23(1):31–41

    Article  PubMed  CAS  Google Scholar 

  35. Wang A et al (2015) Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS One 10(5):e0126312

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Cryan JF et al (2019) The microbiota-gut-brain axis. Physiol Rev

  37. Skonieczna-Żydecka K et al (2018) Microbiome—the missing link in the gut-brain axis: focus on its role in gastrointestinal and mental health. J Clin Med 7(12):521

    Article  PubMed Central  Google Scholar 

  38. Duvallet C et al (2017) Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat Commun 8(1):1–10

    Article  CAS  Google Scholar 

  39. Peng L et al (2009) Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr 139(9):1619–1625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Dalile B et al (2019) The role of short-chain fatty acids in microbiota–gut–brain communication. Nat Rev Gastroenterol Hepatol 16(8):461–478

    Article  PubMed  Google Scholar 

  41. Feng Y et al (2020) Interleukin 17-producing γδ T cell induced demyelination of brain during Angiostrongylus cantonensis infection

  42. Kennedy PJ et al (2017) Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology 112:399–412

    Article  CAS  PubMed  Google Scholar 

  43. Silva YP, Bernardi A, Frozza RL (2020) The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol 11:25

    Article  Google Scholar 

  44. van de Wouw M et al (2018) Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. J Physiol 596(20):4923–4944

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Larsen JM (2017) The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology 151(4):363–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Górska A et al (2019) Probiotic bacteria: a promising tool in cancer prevention and therapy. Curr Microbiol 76(8):939–949

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Segain JP et al (2000) Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn’s disease. Gut 47(3):397–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Bai J, Zhang W (2021) Human microbiome: understanding the role of the gut microbiome and implications for oncology nursing care. Clin J Oncol Nurs 25(4):383–387

    Article  PubMed  PubMed Central  Google Scholar 

  49. Hong QN et al (2018) Mixed methods appraisal tool (MMAT), version 2018. Registration of copyright, 1148552: p. 10

  50. Pluye P et al (2009) A scoring system for appraising mixed methods research, and concomitantly appraising qualitative, quantitative and mixed methods primary studies in Mixed Studies Reviews. Int J Nurs Stud 46(4):529–546

    Article  PubMed  Google Scholar 

  51. Pace R et al (2012) Testing the reliability and efficiency of the pilot Mixed Methods Appraisal Tool (MMAT) for systematic mixed studies review. Int J Nurs Stud 49(1):47–53

    Article  PubMed  Google Scholar 

  52. Su J et al (2018) Effects of different degrees of depression on inflammatory response and immune function in patients with ovarian cancer. J Biol Regul Homeost Agents 32(5):1225–1230

    CAS  PubMed  Google Scholar 

  53. Costanzo ES et al (2005) Psychosocial factors and interleukin-6 among women with advanced ovarian cancer. Cancer Interdiscip Int J Am Cancer Soc 104(2):305–313

    Google Scholar 

  54. Lutgendorf SK et al (2008) Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. J Clin Oncol 26(29):4820–4827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Schrepf A et al (2013) Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability. Brain Behav Immun 30 Suppl(0):S126-34

    Article  PubMed  CAS  Google Scholar 

  56. Armer JS et al (2018) Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer. Cancer 124(16):3401–3408

    Article  CAS  PubMed  Google Scholar 

  57. Kacel EL et al (2019) Interleukin-6 and body mass index, tobacco use, and sleep in gynecologic cancers. Health Psychol 38(10):866

    Article  PubMed  PubMed Central  Google Scholar 

  58. Jakobsson S et al (2010) Exploring a link between fatigue and intestinal injury during pelvic radiotherapy. Oncologist 15(9):1009

    Article  PubMed  PubMed Central  Google Scholar 

  59. Manichanh C et al (2008) The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea. Off J Am Coll Gastroenterol 103(7):1754–1761

    Article  CAS  Google Scholar 

  60. Mitra A et al (2020) Microbial diversity and composition is associated with patient-reported toxicity during chemoradiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys 107(1):163–171

    Article  PubMed  PubMed Central  Google Scholar 

  61. Paulsen Ø et al (2017) The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer. PLoS One 12(5):e0177620

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Fox SW, Lyon D (2007) Symptom clusters and quality of life in survivors of ovarian cancer. Cancer Nurs 30(5):354–361

    Article  PubMed  Google Scholar 

  63. Pedraz-Petrozzi B, Neumann E, Sammer G (2020) Pro-inflammatory markers and fatigue in patients with depression: a case-control study. Sci Rep 10(1):1–12

    Article  CAS  Google Scholar 

  64. Bower JE, Lamkin DM (2013) Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immunol 30:S48–S57

    Article  CAS  Google Scholar 

  65. Kim H-J et al (2012) Common biological pathways underlying the psychoneurological symptom cluster in cancer patients. Cancer Nurs 35(6):E1–E20

    Article  PubMed  Google Scholar 

  66. George MA, Lustberg MB, Orchard TS (2020) Psychoneurological symptom cluster in breast cancer: the role of inflammation and diet. Breast Cancer Res Treat 1–9

  67. Herremans KM et al (2019) The microbiota and cancer cachexia. Int J Mol Sci 20(24):6267

    Article  CAS  PubMed Central  Google Scholar 

  68. Mitra A et al (2020) Microbial diversity and composition is associated with patient-reported toxicity during chemoradiation therapy for cervical cancer. Int J Radiat Oncol Biol Phys 107(1):163–171

    Article  PubMed  PubMed Central  Google Scholar 

  69. Barandouzi ZA et al (2020) Altered composition of gut microbiota in depression: a systematic review. Front Psychiatry 11:541

    Article  PubMed  PubMed Central  Google Scholar 

  70. Iljazovic A et al (2021) Perturbation of the gut microbiome by Prevotella spp. enhances host susceptibility to mucosal inflammation. Mucosal Immunol 14(1):113–124

    Article  CAS  PubMed  Google Scholar 

  71. Zhang X et al (2021) Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients. BMC Microbiol 21(1):1–10

    Article  CAS  Google Scholar 

  72. Belkaid Y, Hand TW (2014) Role of the microbiota in immunity and inflammation. Cell 157(1):121–141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Al Bander Z et al (2020) The gut microbiota and inflammation: an overview. Int J Environ Res Public Health 17(20):7618

    Article  CAS  PubMed Central  Google Scholar 

  74. Sonis ST (2002) The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med 13(5):380–389

    Article  PubMed  Google Scholar 

  75. Matsumoto M, Benno Y (2007) The relationship between microbiota and polyamine concentration in the human intestine: a pilot study. Microbiol Immunol 51(1):25–35

    Article  CAS  PubMed  Google Scholar 

  76. Beg AA (2004) ComPPARtmentalizing NF-κB in the gut. Nat Immunol 5(1):14–16

    Article  CAS  PubMed  Google Scholar 

  77. Sonis ST (2004) A biological approach to mucositis. J Support Oncol 2(1):21–32 (discussion 35-6)

    PubMed  Google Scholar 

  78. Hakansson A, Molin G (2011) Gut microbiota and inflammation. Nutrients 3(6):637–682

    Article  PubMed  PubMed Central  Google Scholar 

  79. Parada Venegas D et al (2019) Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol 10:277

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the support from the Emory University, Woodruff Health Science Library in assisting with the literature search.

Author information

Authors and Affiliations

  1. Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, 30322, USA

    Zahra Amirkhanzadeh Barandouzi, Julia Schrogin, Rebecca Meador & Deborah Watkins Bruner

  2. Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA

    Claire Rowcliffe

  3. Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA

    Deborah Watkins Bruner

Authors
  1. Zahra Amirkhanzadeh Barandouzi
    View author publications

    Search author on:PubMed Google Scholar

  2. Claire Rowcliffe
    View author publications

    Search author on:PubMed Google Scholar

  3. Julia Schrogin
    View author publications

    Search author on:PubMed Google Scholar

  4. Rebecca Meador
    View author publications

    Search author on:PubMed Google Scholar

  5. Deborah Watkins Bruner
    View author publications

    Search author on:PubMed Google Scholar

Contributions

ZAB developed the idea, performed data analysis, and drafted and revised the manuscript. CR performed the literature search, data extraction, and quality assessment. JS performed the literature search, data extraction, quality assessment, and revised the manuscript. RM and DWB drafted and critically revised the work.

Corresponding author

Correspondence to Zahra Amirkhanzadeh Barandouzi.

Ethics declarations

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barandouzi, Z.A., Rowcliffe, C., Schrogin, J. et al. Exploring the links among inflammation and gut microbiome with psychoneurological symptoms and gastrointestinal toxicities in gynecologic cancers: a systematic review. Support Care Cancer 30, 6497–6513 (2022). https://doi.org/10.1007/s00520-022-07027-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-022-07027-0

Keywords