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Fecal Microbes Associated with the Outcomes After Esophagectomy in Patients with Esophageal Cancer

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although accumulating evidence suggests that an imbalanced gut microbiota leads to cancer progression, few studies demonstrated the implication in patients who underwent oncologic esophagectomy. This study aimed to elucidate the association between gut microbes and the outcomes after oncologic esophagectomy, as well as the host’s inflammatory/nutritional status.

Methods

Overall, 783 consecutive patients who underwent oncologic esophagectomy were eligible. We investigated the microbiota detected by fecal culture tests and then assessed the association between the gut microbiota and patient characteristics, short-term outcomes, and long-term survival.

Results

Seventeen different species could be cultivated. We comprehensively examined the impact of each detected microbe on survival. The presence of Bacillus species (Bacillus sp.; 26.8%) was associated with favorable prognosis on overall and cancer-specific survival (p = 0.02 and 0.02, respectively). Conversely, the presence of Proteus mirabilis (P. mirabilis; 3.4%) was associated with unfavorable overall and recurrence-free survivals (p = 0.02 and < 0.01, respectively). Multivariate analysis showed that the presence of P. mirabilis was one of the independent prognostic factors for poor recurrence-free survival (p < 0.01). Patients with Bacillus sp. had lower modified Glasgow prognostic score and better response to preoperative treatment than those without (p = 0.01 and 0.03, respectively). Meanwhile, patients with P. mirabilis were significantly associated with higher systemic inflammation scores and increased postoperative pneumonia incidence than those without (p = 0.01 and 0.02, respectively).

Conclusions

Preoperative fecal microbiota was associated with the host’s inflammatory and nutritional status and may influence the outcomes after oncologic esophagectomy.

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References

  1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  3. Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489:242–9.

    Article  CAS  PubMed  Google Scholar 

  4. Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336:1268–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157:121–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Welsh FK, Ramsden CW, MacLennan K, et al. Increased intestinal permeability and altered mucosal immunity in cholestatic jaundice. Ann Surg. 1998;227:205–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gouma DJ, Coelho JC, Fisher JD, Schlegel JF, Li YF, Moody FG. Endotoxemia after relief of biliary obstruction by internal and external drainage in rats. Am J Surg. 1986;151:476–9.

    Article  CAS  PubMed  Google Scholar 

  8. Vogtmann E, Goedert JJ. Epidemiologic studies of the human microbiome and cancer. Br J Cancer. 2016;114:237–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Garrett WS. Cancer and the microbiota. Science. 2015;348:80–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kovács T, Mikó E, Ujlaki G, Sári Z, Bai P. The microbiome as a component of the tumor microenvironment. Adv Exp Med Biol. 2020;1225:137–53.

    Article  PubMed  Google Scholar 

  11. Zitvogel L, Ayyoub M, Routy B, Kroemer G. Microbiome and anticancer immunosurveillance. Cell. 2016;165:276–87.

    Article  CAS  PubMed  Google Scholar 

  12. Johnson CH, Spilker ME, Goetz L, Peterson SN, Siuzdak G. Metabolite and microbiome interplay in cancer immunotherapy. Cancer Res. 2016;76:6146–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dzutsev A, Goldszmid RS, Viaud S, Zitvogel L, Trinchieri G. The role of the microbiota in inflammation, carcinogenesis, and cancer therapy. Eur J Immunol. 2015;45:17–31.

    Article  CAS  PubMed  Google Scholar 

  14. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13:759–71.

    Article  CAS  PubMed  Google Scholar 

  15. Yuda M, Yamashita K, Okamura A, et al. Influence of preoperative oropharyngeal microflora on the occurrence of postoperative pneumonia and survival in patients undergoing esophagectomy for esophageal cancer. Ann Surg. 2020;272:1035–43.

    Article  PubMed  Google Scholar 

  16. Baba Y, Iwatsuki M, Yoshida N, Watanabe M, Baba H. Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications. Ann Gastroenterol Surg. 2017;1:99–104.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kitagawa Y, Uno T, Oyama T, et al. Esophageal cancer practice guidelines 2017 edited by the Japan Esophageal Society: part 1. Esophagus. 2019;16:1–24.

    Article  PubMed  Google Scholar 

  18. Kitagawa Y, Uno T, Oyama T, et al. Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: Part 2. Esophagus. 2019;16:25–43.

    Article  PubMed  Google Scholar 

  19. Brierley JDGM (eds) WC. TNM classification of malignant tumors. Oxford University Press; 2017. p. 8.

  20. Mayhew D, Mendonca V, Murthy BVS. A review of ASA physical status - historical perspectives and modern developments. Anaesthesia. 2019;74:373–9.

    Article  CAS  PubMed  Google Scholar 

  21. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

    Article  CAS  PubMed  Google Scholar 

  22. Japanese Classification of Esophageal Cancer, 11th edition: Part I. Esophagus. 2017; 14:1–36.

  23. Japanese Classification of Esophageal Cancer, 11th edition: Part II and III. Esophagus. 2017; 14: 37–65.

  24. Inoue Y, Iwata T, Okugawa Y, et al. Prognostic significance of a systemic inflammatory response in patients undergoing multimodality therapy for advanced colorectal cancer. Oncology. 2013;84:100–7.

    Article  CAS  PubMed  Google Scholar 

  25. Chang Y, An H, Xu L, et al. Systemic inflammation score predicts postoperative prognosis of patients with clear-cell renal cell carcinoma. Br J Cancer. 2015;113:626–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Suzuki Y, Okabayashi K, Hasegawa H, et al. Comparison of preoperative inflammation-based prognostic scores in patients with colorectal cancer. Ann Surg. 2018;267:527–31.

    Article  PubMed  Google Scholar 

  27. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  PubMed  Google Scholar 

  28. Yamamura K, Baba Y, Nakagawa S, et al. Human microbiome fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res. 2016;22:5574–81.

    Article  CAS  PubMed  Google Scholar 

  29. Yamamura K, Izumi D, Kandimalla R, et al. Intratumoral fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma. Clin Cancer Res. 2019;25:6170–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chew R, Thomas S, Mantha ML, Killen JP, Cho Y, Baer RA. Large urate cystolith associated with Proteus urinary tract infection. Kidney Int. 2012;81:802.

    Article  PubMed  Google Scholar 

  31. Ahmed M. Acute cholangitis—an update. World J Gastrointest Pathophysiol. 2018;9:1–7.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Singh R, Kumar N, Sundriyal D, Trisal D. Mixed pyogenic and tuberculous liver abscess: clinical suspicion is what matters. BMJ Case Rep. 2013. https://doi.org/10.1136/bcr-2013-008768.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Søgaard KK, Thomsen RW, Schønheyder HC, Søgaard M. Positive predictive values of the International Classification of Diseases, 10th revision diagnoses of Gram-negative septicemia/sepsis and urosepsis for presence of Gram-negative bacteremia. Clin Epidemiol. 2015;7:195–9.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhang J, Hoedt EC, Liu Q, et al. Elucidation of proteus mirabilis as a key bacterium in Crohn’s disease inflammation. Gastroenterology. 2021;160:317-30.e11.

    Article  CAS  PubMed  Google Scholar 

  35. Hamilton AL, Kamm MA, Ng SC, Morrison M. Proteus spp. as putative gastrointestinal pathogens. Clin Microbiol Rev. 31(3):e00085-17.

  36. Chen CY, Chen YH, Lu PL, Lin WR, Chen TC, Lin CY. Proteus mirabilis urinary tract infection and bacteremia: risk factors, clinical presentation, and outcomes. J Microbiol Immunol Infect. 2012;45:228–36.

    Article  CAS  PubMed  Google Scholar 

  37. Sheweita SA, Alsamghan AS. Molecular mechanisms contributing bacterial infections to the incidence of various types of cancer. Mediators Inflamm. 2020;2020:4070419.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zhang H, Diao H, Jia L, et al. Proteus mirabilis inhibits cancer growth and pulmonary metastasis in a mouse breast cancer model. PLoS One. 2017;12:e0188960.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tam NK, Uyen NQ, Hong HA, et al. The intestinal life cycle of Bacillus subtilis and close relatives. J Bacteriol. 2006;188:2692–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Casula G, Cutting SM. Bacillus probiotics: spore germination in the gastrointestinal tract. Appl Environ Microbiol. 2002;68:2344–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. le Duc H, Hong HA, Barbosa TM, Henriques AO, Cutting SM. Characterization of Bacillus probiotics available for human use. Appl Environ Microbiol. 2004;70:2161–71.

    Article  CAS  PubMed Central  Google Scholar 

  42. Piewngam P, Zheng Y, Nguyen TH, et al. Pathogen elimination by probiotic Bacillus via signalling interference. Nature. 2018;562:532–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hong HA, le Duc H, Cutting SM. The use of bacterial spore formers as probiotics. FEMS Microbiol Rev. 2005;29:813–35.

    Article  CAS  PubMed  Google Scholar 

  44. Fujiya M, Musch MW, Nakagawa Y, et al. The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. Cell Host Microbe. 2007;1:299–308.

    Article  CAS  PubMed  Google Scholar 

  45. Mohamed SS, Ibrahim AY, Asker MS, Mahmoud MG, El-Newary SA. Production, structural and biochemical characterization relevant to antitumor property of acidic exopolysaccharide produced from Bacillus sp. NRC5. Arch Microbiol. 2021;203:4337–50.

    Article  CAS  PubMed  Google Scholar 

  46. Zheng L, Zhu X, Yang K, et al. PBN11-8, a cytotoxic polypeptide purified from marine bacillus, suppresses invasion and migration of human hepatocellular carcinoma cells by targeting focal adhesion kinase pathways. Polymers (Basel). 2018;10(9):1043.

    Article  PubMed Central  Google Scholar 

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Acknowledgment

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Suguru Maruyama MD, PhD, Akihiko Okamura MD, PhD, Yasukazu Kanie MD, Kei Sakamoto MD, Daisuke Fujiwara MD, PhD, Jun Kanamori MD, PhD, Yu Imamura MD, PhD, FACS & Masayuki Watanabe MD, PhD, FACS

  2. Department of Infectious Disease, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Koichi Takeda MD

Authors
  1. Suguru Maruyama MD, PhD
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  2. Akihiko Okamura MD, PhD
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  3. Yasukazu Kanie MD
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  4. Kei Sakamoto MD
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  5. Daisuke Fujiwara MD, PhD
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  6. Jun Kanamori MD, PhD
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  8. Koichi Takeda MD
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  9. Masayuki Watanabe MD, PhD, FACS
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Correspondence to Akihiko Okamura MD, PhD.

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Disclosure

Suguru Maruyama, Akihiko Okamura, Yasukazu Kanie, Kei Sakamoto, Daisuke Fujiwara, Jun Kanamori, Yu Imamura, Koichi Takeda, and Masayuki Watanabe declare no conflicts of interest.

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Maruyama, S., Okamura, A., Kanie, Y. et al. Fecal Microbes Associated with the Outcomes After Esophagectomy in Patients with Esophageal Cancer. Ann Surg Oncol 29, 7448–7457 (2022). https://doi.org/10.1245/s10434-022-12166-z

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  • DOI: https://doi.org/10.1245/s10434-022-12166-z

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