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Gut microbio­me and pancreatic cancer


Authors: M. Eid 1;  A. Martínek 2;  J. Dolina 3;  M. Uvírová 4;  P. Dítě 3
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno 1;  Interní kardiologická klinika LF OU a FN Ostrava 2;  Interní gastroenterologická klinika LF MU a FN Brno 3;  UCB Laboratoř CGB Ostrava 4
Published in: Klin Onkol 2024; 38(1): 20-26
Category: Reviews
doi: https://doi.org/10.48095/ccko202420

Overview

Background: The incidence of pancreatic cancer (pancreatic ductal adenocarcinoma – PDAC) is increasing, especially in developed countries. In 2021, 496,000 new PDAC cases were dia­gnosed worldwide. In the Czech Republic, the incidence is one of the highest in the world, with 2,332 new PDAC patients dia­gnosed in 2018. Due to the absence of symptoms in the early stages, approximately 50% of patients are initially dia­gnosed with distant metastases. Mortality is slightly lower than the incidence count and, despite significant advances in cancer research, PDAC remains a fatal dia­gnosis. However, microbio­me seems to be an interesting approach, and not only in PDAC patients. Microbio­me is defined as the set of all microorganisms (microbio­ta, i.e. bacteria, fungi, viruses, archaea, and protozoa) and their genome in a certain environment. In a physiological setting, the gut microbio­me is in symbio­sis with the host organism, maintaining the balance of metabolism, mucosal immunomodulation and regulating the digestion process. When dysregulation of the number or function of intestinal microorganisms occurs, dysbio­sis is developed. It may lead to metabolic and cardiovascular diseases, nervous system disorders, induction of intestinal inflammation, or carcinogenesis. Microbio­ta can induce carcinogenesis in multiple ways, such as by activating an inflammatory response, reducing the immune system‘s ability to eliminate damaged cells, and deregulation of the host genome by microbial metabolites. This deregulation may lead to an activation of pro-apoptotic and pro-proliferative proteins. To date, research shows that the gut or oral microbio­me may be involved in the development of PDAC. One of the most studied bacteria is Porphyromonas gingivalis. Other bacteria, such as Fusobacteria, Enterobacter, Klebsiella, Prevotella, and Rothia, have also been shown to play a role in PDAC. Purpose: The aim of this review article is to point out one of the possible mechanisms of cancerogenesis in PDAC patients and its therapeutic influence to reduce the incidence and improve the prognosis of this aggressive disease.

Keywords:

Bacteria – microbio­me – pancreatic carcinoma − dysbio­sis


Sources

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(3): 209–249. doi: 10.3322/ caac.21660.

2. ÚZIS ČR. Zdravotnická ročenka České republiky 2021. [online]. Dostupné z: https:/ / www.uzis.cz/ res/ f/ 00 8435/ zdrroccz2021.pdf.

3. Li J, Li Y, Chen C et al. Recent estimates and predictions of 5-year survival rate in patients with pancreatic cancer: a model-based period analysis. Front Med (Lausanne) 2022; 9: 1049136. doi: 10.3389/ fmed.2022.1049136.

4. Bratlie SO, Wennerblom J, Vilhav C et al. Resectable, borderline, and locally advanced pancreatic cancer – „the good, the bad, and the ugly“ candidates for surgery? J Gastrointest Oncol 2021; 12(5): 2450–2460. doi: 10.21037/ jgo-2020-slapc-04.

5. Haeno H, Gonen M, Davis MB et al. Computational modeling of pancreatic cancer reveals kinetics of metastasis suggesting optimum treatment strategies. Cell 2012; 148(1–2): 362–375. doi: 10.1016/ j.cell.2011.11.060.

6. Klein AP. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol 2021; 18(7): 493–502. doi: 10.1038/ s41575-021-00457-x.

7. Wolrab D, Jirásko R, Cífková E et al. Lipidomic profiling of human serum enables detection of pancreatic cancer. Nat Commun 2022; 13(1): 124. doi: 10.1038/ s41467-021-27765-9.

8. Belkaid Y, Hand TW. Role of microbio­ta in immunity and inflammation cells. Cell 2014; 157(1): 121–141. doi: 10.1016/ j.cell.2014.03.011.

9. Illiano P, Brambilla R, Parolini C. The mutual interplay of gut microbio­ta, diet and human disease. FEBS J 2020; 287(5): 833–855. doi: 10.1111/ febs.15217.

10. Abdul Rahman R, Lamarca A, Hubner RA et al. The microbio­me as a potential target for therapeutic manipulation in pancreatic cancer. Cancers (Basel) 2021; 13(15): 3779. doi: 10.3390/ cancers13153779.

11. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984; 1(8390): 1311–1315. doi: 10.1016/ s0140-6736(84)91816-6.

12. Rai AK, Panda M, Das AK et al. Dysbio­sis of salivary microbio­me and cytokines influence oral squamous cell carcinoma through inflammation. Arch Microbio­l 2021; 203(1): 137–152. doi: 10.1007/ s00203-020-02011-w.

13. Lennard KS, Goosen RW, Blackburn JM. Bacterially-associated transcriptional remodelling in a distinct genomic subtype of colorectal cancer provides a plausible molecular basis for disease development. PLoS One 2016; 11(11): e0166282. doi: 10.1371/ journal.pone.0166282.

14. Zwinsová B, Brychtová V, Hrivňáková M et al. Role of the microbio­me in the formation and development of colorectal cancer. Klin Onkol 2019; 32(4): 261–269. doi: 10.14735/ amko2019261.

15. Reitano E, de‘Angelis N, Gavriilidis P et al. Oral bacterial microbio­ta in digestive cancer patients: a systematic review. Microorganisms 2021; 9(12): 2585. doi: 10.3390/ microorganisms9122585.

16. Ren Z, Jiang J, Xie H et al. Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China. Oncotarget 2017; 8(56): 95176–95191. doi: 10.18632/ oncotarget.18820.

17. Fan X, Alekseyenko AV, Wu J et al. Human oral microbio­me and prospective risk for pancreatic cancer: a population-based nested case-control study. Gut 2018; 67(1): 120–127. doi: 10.1136/ gutjnl-2016-312580.

18. Nejman D, Livyatan I, Fuks G et al. The human tumor microbio­me is composed of tumor type-specific intracellular bacteria. Science 2020; 368(6494): 973–980. doi: 10.1126/ science.aay9189.

19. Fukuda A, Wang SC, Morris JP et al. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell 2011; 19(4):
441–455. doi: 10.1016/ j.ccr.2011.03.002.

20. Lesina M, Kurkowski MU, Ludes K et al. Stat3/ Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 2011; 19(4): 456–469. doi: 10.1016/ j.ccr.2011.03.009.

21. Sethi V, Vitiello GA, Saxena D et al. The role of the microbio­me in immunologic development and its implication for pancreatic cancer immunotherapy. Gastroenterology 2019; 156(7): 2097–2115.e2. doi: 10.1053/ j.gastro.2018.12.045.

22. Wei MY, Shi S, Liang C et al. The microbio­ta and microbio­me in pancreatic cancer: more influential than expected. Mol Cancer 2019; 18(1): 97. doi: 10.1186/ s12943-019-1008-0.

23. Wang X, Jia Y, Wen L et al. Porphyromonas gingivalis promotes colorectal carcinoma by activating the hema­topoietic NLRP3 inflammasome. Cancer Res 2021; 81(10): 2745–2759. doi: 10.1158/ 0008-5472.CAN-20-3827.

24. Meng F, Li R, Ma L et al. Porphyromonas gingivalis promotes the motility of esophageal squamous cell carcinoma by activating NF-kB signaling pathway. Microbes Infect 2019; 21(7): 296–304. doi: 10.1016/ 
j.micinf.2019.01.005.

25. Utispan K, Pugdee K, Koontongkaew S. Porphyromonas gingivalis lipopolysaccharide-induced macrophages modulate proliferation and invasion of head and neck cancer cell lines. Biomed Pharmacother 2018; 101: 988–995. doi: 10.1016/ j.bio­pha.2018.03.033.

26. Jesnowski R, Isaksson B, Möhrcke C et al. Helicobacter pylori in autoimmune pancreatitis and pancreatic carcinoma. Pancreatology 2010; 10(4): 462–466. doi: 10.1159/ 000264677.

27. Tijeras-Raballand A, Hilmi M, Astorgues-Xerri L et al. Microbio­me and pancreatic ductal adenocarcinoma. Clin Res Hepatol Gastroenterol 2021; 45(2): 101589. doi: 10.1016/ j.clinre.2020.101589.

28. Geller LT, Barzily-Rokni M, Danino T et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 2017; 357(6356): 1156–1160. doi: 10.1126/ science.aah5043.

29. Gaiser RA, Halimi A, Alkharaan H et al. Enrichment of oral microbio­ta in early cystic precursors to invasive pancreatic cancer. Gut 2019; 68(12): 2186–2194. doi: 10.1136/ gutjnl-2018-317458.

30. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology 2013; 144(6): 1252–1261. doi: 10.1053/ j.gastro.2013.01.068.

31. Del Castillo E, Meier R, Chung M et al. The microbio­mes of pancreatic and duodenum tissue overlap and are highly subject specific but differ between pancreatic cancer and noncancer subjects. Cancer Epidemiol Biomarkers Prev 2019; 28(2): 370–383. doi: 10.1158/ 1055-9965.
EPI-18-0542.

32. Kohi S, Macgregor-Das A, Dbouk M et al. Alterations in the duodenal fluid microbio­me of patients with pancreatic cancer. Clin Gastroenterol Hepatol 2022; 20(2): e196–e227. doi: 10.1016/ j.cgh.2020.11.006.

33. Masi AC, Oppong YEA, Haugk B et al. Endoscopic ultrasound (EUS) – guided fine needle bio­psy (FNB) formalin fixed paraffin-embedded (FFPE) pancreatic tissue samples are a potential resource for microbio­ta analysis. Gut 2021; 70(5): 999–1001. doi: 10.1136/ gutjnl-2020-322
457.

34. Grander C, Adolph TE, Wieser V et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut 2018; 67(5): 891–901. doi: 10.1136/ gutjnl-2016-313432.

35. Goodrich JK, Waters JL, Poole AC et al. Human genetics shape the gut microbio­me. Cell 2014; 159(4): 789–799. doi: 10.1016/ j.cell.2014.09.053.

36. Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer 2003; 3(4): 276–285. doi: 10.1038/ nrc1046.

37. Lee CJ, Sears CL, Maruthur N. Gut microbio­me and its role in obesity and insulin resistance. Ann N Y Acad Sci 2020; 1461(1): 37–52. doi: 10.1111/ nyas.14107.

38. Piya MK, McTernan PG, Kumar S. Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin. J Endocrinol 2013; 216(1): T1–T15. doi: 10.1530/ JOE-12-0498.

39. Hakkak R, Korourian S, Foley SL et al. Assessment of gut microbio­ta populations in lean and obese Zucker rats. PLoS One 2017; 12(7): e0181451. doi: 10.1371/ journal.pone.0181451.

40. Craciun CI, Neag MA, Catinean A et al. The relationships between gut microbio­ta and diabetes mellitus, and treatments for diabetes mellitus. Biomedicines 2022; 10(2): 308. doi: 10.3390/ bio­medicines10020308.

41. Song S, Wang B, Zhang X et al. Long-term diabetes mellitus is associated with an increased risk of pancreatic cancer: a meta-analysis. PLoS One 2015; 10(7): e0134321. doi: 10.1371/ journal.pone.0134321.

42. Zhang N, Ju Z, Zuo T. Time for food: the impact of diet on gut microbio­ta and human health. Nutrition 2018;
51–52: 80–85. doi: 10.1016/ j.nut.2017.12.005.

43. Wu C, Li M, Chen W. Characteristics of gut microbio­ta in cerulein-induced chronic pancreatitis. Diabetes Metab Syndr Obes 2021; 14: 285–294. doi: 10.2147/ DMSO.S291822.

44. Raimondi S, Lowenfels AB, Morselli-Labate AM et al. Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection. Best Pract Res Clin Gastroenterol 2010; 24(3): 349–358. doi: 10.1016/ j.bpg.2010.02.007.

45. Capurso G, Signoretti M, Archibugi L et al. Systematic review and meta-analysis: small intestinal bacterial overgrowth in chronic pancreatitis. United European Gastroenterol J 2016; 4(5): 697–705. doi: 10.1177/ 20 50640616630117.

46. Guerra C, Schuhmacher AJ, Cañamero M et al. Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 2007; 11(3): 291–302. doi: 10.1016/ 
j.ccr.2007.01.012.

47. Bartolini I, Nannini G, Risaliti M et al. Impact of microbio­ta-immunity axis in pancreatic cancer management. World J Gastroenterol 2022; 28(32): 4527–4539. doi: 10.3748/ wjg.v28.i32.4527.

48. Farrell JJ, Zhang L, Zhou H et al. Variations of oral microbio­ta are associated with pancreatic diseases including pancreatic cancer. Gut 2012; 61(4): 582–588. doi: 10.1136/ gutjnl-2011-300784.

49. Baunwall SMD, Lee MM, Eriksen MK et al. Faecal microbio­ta transplantation for recurrent Clostridioides difficile infection: an updated systematic review and meta-analysis. EClinicalMedicine 2020; 29–30: 100642. doi: 10.1016/ j.eclinm.2020.100642.

50. Riquelme E, Zhang Y, Zhang L et al. Tumor microbio­me diversity and composition influence pancreatic cancer outcomes. Cell 2019; 178(4): 795–806.e12. doi: 10.1016/
 j.cell.2019.07.008.

51. Imbuluzqueta E, Gamazo C, Ariza J et al. Drug delivery systems for potential treatment of intracellular bacterial infections. Front Biosci (Landmark Ed) 2010; 15(2):
397–417. doi: 10.2741/ 3627.

52. Mohindroo C, Hasanov M, Rogers JE et al. Antibio­tic use influences outcomes in advanced pancreatic adenocarcinoma patients. Cancer Med 2021; 10(15): 5041–5050. doi: 10.1002/ cam4.3870.

53. Hasanov M, Mohindroo C, Rogers J et al. The effect of antibio­tic use on survival of patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol 2019; 37 (Suppl 15): e15773. doi: 10.1200/ JCO.2019.37.15_suppl.e15773.

54. Meng C, Bai C, Brown TD et al. Human gut microbio­ta and gastrointestinal cancer. Genomics Proteomics Bioinformatics 2018; 16(1): 33–49. doi: 10.1016/ j.gpb.2017. 06.002.

55. Derosa L, Zitvogel L. A probio­tic supplement boosts response to cancer immunotherapy. Nat Med 2022; 28(4): 633–634. doi: 10.1038/ s41591-022-01723-4.

56. Duckworth DH, Gulig PA. Bacteriophages: potential treatment for bacterial infections. BioDrugs 2002; 16(1): 57–62. doi: 10.2165/ 00063030-200216010-00
006.

57. Kabwe M, Dashper S, Bachrach G et al. Bacteriophage manipulation of the microbio­me associated with tumour microenvironments-can this improve cancer therapeutic response? FEMS Microbio­l Rev 2021; 45(5): fuab017. doi: 10.1093/ femsre/ fuab017.

58. Yang O, Zhang J, Zhu Y. Potential roles of gut microbio­ta in pancreatic cancerogenesis and therapeutics. Front Cel Infect Microbio­l 2022; 12: 872019. doi: 10.3389/ fcimb.2022.872019.

59. Farrow B, Rychahou P, O‘Connor KL et al. Butyrate inhibits pancreatic cancer invasion. J Gastrointest Surg 2003; 7(7): 864–870. doi: 10.1007/ s11605-003-00
31-y.

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