Research progress of correlation between gastric cancer and non-<i>Helicobacter pylori</i> gastric microbes_West China Medical Journal

Authors：

WU Lili ¹ , XU Zhihong ¹ , ZHANG Xiumei ¹ ,  HE Suyu ^1,2

1. Graduate School of Zunyi Medical University, Zunyi, Guizhou 563000, P. R. China;
2. The Fourth Department of Digestive Disease Center, Suining Central Hospital, Suining, Sichuan 629000, P. R. China;

Corresponding author：

HE Suyu, Email: hesuyu2009@163.com

Keywords：

Helicobacter pylori; gastric microbes; gastric cancer; atrophy; intestinal metaplasia

DOI：

10.7507/1002-0179.202212072

Video：

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Gastric cancer is common as one kind of digestive tract malignant tumor, and Helicobacter pylori (Hp) infection is the most important cause of gastric cancer. With the wide application of quadruple therapy, the incidence of Hp-related gastric cancer has been significantly decreased. In addition to the involvement of gastric microbes in the regulation of normal gastric physiological function, the imbalance of gastric microbes is also involved in the pathogenesis of gastritis and gastric cancer. The imbalance of gastric microbes also plays an important role in the development of gastric cancer after eradication of Hp, and the mechanism has also been preliminary studied. Based on this, this article reviews the research progress of gastric microbes in gastric cancer, in order to further understand the pathogenic mechanism of gastric cancer and provide reference for seeking safer and more effective treatment for gastric cancer.

Citation： WU Lili, XU Zhihong, ZHANG Xiumei, HE Suyu. Research progress of correlation between gastric cancer and non-Helicobacter pylori gastric microbes. West China Medical Journal, 2023, 38(8): 1236-1242. doi: 10.7507/1002-0179.202212072 Copy

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2.	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.
3.	Cao MM, Li H, Sun DQ, et al. Current cancer burden in China: epidemiology, etiology, and prevention. Cancer Biol Med, 2022, 19(8): 1121-1138.
4.	Qiu H, Cao S, Xu R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020. Cancer Commun (Lond), 2021, 41(10): 1037-1048.
5.	Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol, 2022, 33(10): 1005-1020.
6.	Xu W, Xu L, Xu C. Relationship between Helicobacter pylori infection and gastrointestinal microecology. Front Cell Infect Microbiol, 2022, 12: 938608.
7.	Öztekin M, Yılmaz B, Ağagündüz D, et al. Overview of Helicobacter pylori infection: clinical features, treatment, and nutritional aspects. Diseases, 2021, 9(4): 66.
8.	Huang Q, Jia X, Chu Y, et al. Helicobacter pylori infection in geriatric patients: current situation and treatment regimens. Front Med (Lausanne), 2021, 8: 713908.
9.	Rugge M, Genta RM, Malfertheiner P, et al. Steps forward in understanding gastric cancer risk. Gut, 2023, 72(9): 1802-1803.
10.	Li Q, Yu H. The role of non-H. pylori bacteria in the development of gastric cancer. Am J Cancer Res, 2020, 10(8): 2271-2281.
11.	Van den Abbeele P, Van de Wiele T, Verstraete W, et al. The host selects mucosal and luminal associations of coevolved gut microorganisms: a novel concept. FEMS Microbiol Rev, 2011, 35(4): 681-704.
12.	Qu P, Liu X, Xia X, et al. Saccharomyces boulardii allows partial patients to avoid reusing bismuth quadruple for Helicobacter pylori rescue therapy: a single-center randomized controlled study. Front Cell Infect Microbiol, 2022, 12: 903002.
13.	Shen Z, Dzink-Fox J, Feng Y, et al. Gastric non-Helicobacter pylori urease-positive Staphylococcus epidermidis and Streptococcus salivarius isolated from humans have contrasting effects on H. pylori-associated gastric pathology and host immune responses in a murine model of gastric cancer. mSphere, 2022, 7(1): e0077221.
14.	Sacco MA, Abenavoli L, Juan C, et al. Biological mechanisms behind Wischnewsky spots finding on gastric mucosa: autopsy cases and literature review. Int J Environ Res Public Health, 2022, 19(6): 3601.
15.	Vergara X, Schep R, Medema RH, et al. From fluorescent foci to sequence: illuminating DNA double strand break repair by high-throughput sequencing technologies. DNA Repair (Amst), 2022, 118: 103388.
16.	Monstein HJ, Tiveljung A, Kraft CH, et al. Profiling of bacterial flora in gastric biopsies from patients with Helicobacter pylori-associated gastritis and histologically normal control individuals by temperature gradient gel electrophoresis and 16S rDNA sequence analysis. J Med Microbiol, 2000, 49(9): 817-822.
17.	Bik EM, Eckburg PB, Gill SR, et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci U S A, 2006, 103(3): 732-737.
18.	Wen J, Lau HC, Peppelenbosch M, et al. Gastric microbiota beyond H. pylori: an emerging critical character in gastric carcinogenesis. Biomedicines, 2021, 9(11): 1680.
19.	Wang D, Zhang T, Lu Y, et al. Helicobacter pylori infection affects the human gastric microbiome, as revealed by metagenomic sequencing. FEBS Open Bio, 2022, 12(6): 1188-1196.
20.	Sugihartono T, Fauzia KA, Miftahussurur M, et al. Analysis of gastric microbiota and Helicobacter pylori infection in gastroesophageal reflux disease. Gut Pathog, 2022, 14(1): 38.
21.	Lei C, Gong D, Zhuang B, et al. Alterations in the gastric microbiota and metabolites in gastric cancer: an update review. Front Oncol, 2022, 12: 960281.
22.	Ndegwa N, Ploner A, Andersson AF, et al. Gastric microbiota in a low-Helicobacter pylori prevalence general population and their associations with gastric lesions. Clin Transl Gastroenterol, 2020, 11(7): e00191.
23.	Dooyema SDR, Noto JM, Wroblewski LE, et al. Helicobacter pylori actively suppresses innate immune nucleic acid receptors. Gut Microbes, 2022, 14(1): 2105102.
24.	Huang G, Wang S, Wang J, et al. Bile reflux alters the profile of the gastric mucosa microbiota. Front Cell Infect Microbiol, 2022, 12: 940687.
25.	Zhao Y, Li Z, Zhao L, et al. Two novel lactic acid bacteria, Limosilactobacillus fermentum MN-LF23 and Lactobacillus gasseri MN-LG80, inhibited Helicobacter pylori infection in C57BL/6 mice. Food Funct, 2022, 13(21): 11061-11069.
26.	Abate M, Vos E, Gonen M, et al. A novel microbiome signature in gastric cancer: a two independent cohort retrospective analysis. Ann Surg, 2022, 276(4): 605-615.
27.	Hu YL, Pang W, Huang Y, et al. The gastric microbiome is perturbed in advanced gastric adenocarcinoma identified through shotgun metagenomics. Front Cell Infect Microbiol, 2018, 8: 433.
28.	Liu D, Chen S, Gou Y, et al. Gastrointestinal microbiota changes in patients with gastric precancerous lesions. Front Cell Infect Microbiol, 2021, 11: 749207.
29.	Kwon SK, Park JC, Kim KH, et al. Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut, 2022, 71(7): 1266-1276.
30.	Liu D, Zhang R, Chen S, et al. Analysis of gastric microbiome reveals three distinctive microbial communities associated with the occurrence of gastric cancer. BMC Microbiol, 2022, 22(1): 184.
31.	Zhou CB, Pan SY, Jin P, et al. Fecal signatures of Streptococcus anginosus and Streptococcus constellatus for noninvasive screening and early warning of gastric cancer. Gastroenterology, 2022, 162(7): 1933-1947.
32.	Coker OO, Dai Z, Nie Y, et al. Mucosal microbiome dysbiosis in gastric carcinogenesis. Gut, 2018, 67(6): 1024-1032.
33.	Liu C, Ng SK, Ding Y, et al. Meta-analysis of mucosal microbiota reveals universal microbial signatures and dysbiosis in gastric carcinogenesis. Oncogene, 2022, 41(28): 3599-3610.
34.	Chen CC, Liou JM, Lee YC, et al. The interplay between Helicobacter pylori and gastrointestinal microbiota. Gut Microbes, 2021, 13(1): 1-22.
35.	Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol, 2010, 25(3): 479-486.
36.	Hara D, Okamura T, Iwaya Y, et al. Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development. Helicobacter, 2022, 27(6): e12934.
37.	Doorakkers E, Lagergren J, Engstrand L, et al. Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population. Gut, 2018, 67(12): 2092-2096.
38.	Kumar S, Metz DC, Ellenberg S, et al. Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study. Gastroenterology, 2020, 158(3): 527-536.
39.	Alarcón T, Llorca L, Perez-Perez G. Impact of the microbiota and gastric disease development by Helicobacter pylori. Curr Top Microbiol Immunol, 2017, 400: 253-275.
40.	Li L, Zhou X, Xiao S, et al. The effect of Helicobacter pylori eradication on the gastrointestinal microbiota in patients with duodenal ulcer. J Gastrointestin Liver Dis, 2016, 25(2): 139-146.
41.	He C, Peng C, Wang H, et al. The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults. Helicobacter, 2019, 24(4): e12590.
42.	Jin D, Huang K, Xu M, et al. Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota. Gut Microbes, 2022, 14(1): 2120744.
43.	Nascimento Araujo CD, Amorim AT, Barbosa MS, et al. Evaluating the presence of Mycoplasma hyorhinis, Fusobacterium nucleatum, and Helicobacter pylori in biopsies of patients with gastric cancer. Infect Agent Cancer, 2021, 16(1): 70.
44.	He C, Peng C, Shu X, et al. Convergent dysbiosis of gastric mucosa and fluid microbiome during stomach carcinogenesis. Gastric Cancer, 2022, 25(5): 837-849.
45.	Peng R, Liu S, You W, et al. Gastric microbiome alterations are associated with decreased CD8⁺ tissue-resident memory T cells in the tumor microenvironment of gastric cancer. Cancer Immunol Res, 2022, 10(10): 1224-1240.
46.	Yang Y, Dai D, Jin W, et al. Microbiota and metabolites alterations in proximal and distal gastric cancer patients. J Transl Med, 2022, 20(1): 439.
47.	Morgan AD, Seely KD, Hagenstein LD, et al. Bacterial involvement in progression and metastasis of adenocarcinoma of the stomach. Cancers (Basel), 2022, 14(19): 4886.
48.	Hsieh YY, Tung SY, Pan HY, et al. Fusobacterium nucleatum colonization is associated with decreased survival of Helicobacter pylori-positive gastric cancer patients. World J Gastroenterol, 2021, 27(42): 7311-7323.

1. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2022, 20(2): 167-192.
2. 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.
3. Cao MM, Li H, Sun DQ, et al. Current cancer burden in China: epidemiology, etiology, and prevention. Cancer Biol Med, 2022, 19(8): 1121-1138.
4. Qiu H, Cao S, Xu R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020. Cancer Commun (Lond), 2021, 41(10): 1037-1048.
5. Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol, 2022, 33(10): 1005-1020.
6. Xu W, Xu L, Xu C. Relationship between Helicobacter pylori infection and gastrointestinal microecology. Front Cell Infect Microbiol, 2022, 12: 938608.
7. Öztekin M, Yılmaz B, Ağagündüz D, et al. Overview of Helicobacter pylori infection: clinical features, treatment, and nutritional aspects. Diseases, 2021, 9(4): 66.
8. Huang Q, Jia X, Chu Y, et al. Helicobacter pylori infection in geriatric patients: current situation and treatment regimens. Front Med (Lausanne), 2021, 8: 713908.
9. Rugge M, Genta RM, Malfertheiner P, et al. Steps forward in understanding gastric cancer risk. Gut, 2023, 72(9): 1802-1803.
10. Li Q, Yu H. The role of non-H. pylori bacteria in the development of gastric cancer. Am J Cancer Res, 2020, 10(8): 2271-2281.
11. Van den Abbeele P, Van de Wiele T, Verstraete W, et al. The host selects mucosal and luminal associations of coevolved gut microorganisms: a novel concept. FEMS Microbiol Rev, 2011, 35(4): 681-704.
12. Qu P, Liu X, Xia X, et al. Saccharomyces boulardii allows partial patients to avoid reusing bismuth quadruple for Helicobacter pylori rescue therapy: a single-center randomized controlled study. Front Cell Infect Microbiol, 2022, 12: 903002.
13. Shen Z, Dzink-Fox J, Feng Y, et al. Gastric non-Helicobacter pylori urease-positive Staphylococcus epidermidis and Streptococcus salivarius isolated from humans have contrasting effects on H. pylori-associated gastric pathology and host immune responses in a murine model of gastric cancer. mSphere, 2022, 7(1): e0077221.
14. Sacco MA, Abenavoli L, Juan C, et al. Biological mechanisms behind Wischnewsky spots finding on gastric mucosa: autopsy cases and literature review. Int J Environ Res Public Health, 2022, 19(6): 3601.
15. Vergara X, Schep R, Medema RH, et al. From fluorescent foci to sequence: illuminating DNA double strand break repair by high-throughput sequencing technologies. DNA Repair (Amst), 2022, 118: 103388.
16. Monstein HJ, Tiveljung A, Kraft CH, et al. Profiling of bacterial flora in gastric biopsies from patients with Helicobacter pylori-associated gastritis and histologically normal control individuals by temperature gradient gel electrophoresis and 16S rDNA sequence analysis. J Med Microbiol, 2000, 49(9): 817-822.
17. Bik EM, Eckburg PB, Gill SR, et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci U S A, 2006, 103(3): 732-737.
18. Wen J, Lau HC, Peppelenbosch M, et al. Gastric microbiota beyond H. pylori: an emerging critical character in gastric carcinogenesis. Biomedicines, 2021, 9(11): 1680.
19. Wang D, Zhang T, Lu Y, et al. Helicobacter pylori infection affects the human gastric microbiome, as revealed by metagenomic sequencing. FEBS Open Bio, 2022, 12(6): 1188-1196.
20. Sugihartono T, Fauzia KA, Miftahussurur M, et al. Analysis of gastric microbiota and Helicobacter pylori infection in gastroesophageal reflux disease. Gut Pathog, 2022, 14(1): 38.
21. Lei C, Gong D, Zhuang B, et al. Alterations in the gastric microbiota and metabolites in gastric cancer: an update review. Front Oncol, 2022, 12: 960281.
22. Ndegwa N, Ploner A, Andersson AF, et al. Gastric microbiota in a low-Helicobacter pylori prevalence general population and their associations with gastric lesions. Clin Transl Gastroenterol, 2020, 11(7): e00191.
23. Dooyema SDR, Noto JM, Wroblewski LE, et al. Helicobacter pylori actively suppresses innate immune nucleic acid receptors. Gut Microbes, 2022, 14(1): 2105102.
24. Huang G, Wang S, Wang J, et al. Bile reflux alters the profile of the gastric mucosa microbiota. Front Cell Infect Microbiol, 2022, 12: 940687.
25. Zhao Y, Li Z, Zhao L, et al. Two novel lactic acid bacteria, Limosilactobacillus fermentum MN-LF23 and Lactobacillus gasseri MN-LG80, inhibited Helicobacter pylori infection in C57BL/6 mice. Food Funct, 2022, 13(21): 11061-11069.
26. Abate M, Vos E, Gonen M, et al. A novel microbiome signature in gastric cancer: a two independent cohort retrospective analysis. Ann Surg, 2022, 276(4): 605-615.
27. Hu YL, Pang W, Huang Y, et al. The gastric microbiome is perturbed in advanced gastric adenocarcinoma identified through shotgun metagenomics. Front Cell Infect Microbiol, 2018, 8: 433.
28. Liu D, Chen S, Gou Y, et al. Gastrointestinal microbiota changes in patients with gastric precancerous lesions. Front Cell Infect Microbiol, 2021, 11: 749207.
29. Kwon SK, Park JC, Kim KH, et al. Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut, 2022, 71(7): 1266-1276.
30. Liu D, Zhang R, Chen S, et al. Analysis of gastric microbiome reveals three distinctive microbial communities associated with the occurrence of gastric cancer. BMC Microbiol, 2022, 22(1): 184.
31. Zhou CB, Pan SY, Jin P, et al. Fecal signatures of Streptococcus anginosus and Streptococcus constellatus for noninvasive screening and early warning of gastric cancer. Gastroenterology, 2022, 162(7): 1933-1947.
32. Coker OO, Dai Z, Nie Y, et al. Mucosal microbiome dysbiosis in gastric carcinogenesis. Gut, 2018, 67(6): 1024-1032.
33. Liu C, Ng SK, Ding Y, et al. Meta-analysis of mucosal microbiota reveals universal microbial signatures and dysbiosis in gastric carcinogenesis. Oncogene, 2022, 41(28): 3599-3610.
34. Chen CC, Liou JM, Lee YC, et al. The interplay between Helicobacter pylori and gastrointestinal microbiota. Gut Microbes, 2021, 13(1): 1-22.
35. Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol, 2010, 25(3): 479-486.
36. Hara D, Okamura T, Iwaya Y, et al. Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development. Helicobacter, 2022, 27(6): e12934.
37. Doorakkers E, Lagergren J, Engstrand L, et al. Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population. Gut, 2018, 67(12): 2092-2096.
38. Kumar S, Metz DC, Ellenberg S, et al. Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study. Gastroenterology, 2020, 158(3): 527-536.
39. Alarcón T, Llorca L, Perez-Perez G. Impact of the microbiota and gastric disease development by Helicobacter pylori. Curr Top Microbiol Immunol, 2017, 400: 253-275.
40. Li L, Zhou X, Xiao S, et al. The effect of Helicobacter pylori eradication on the gastrointestinal microbiota in patients with duodenal ulcer. J Gastrointestin Liver Dis, 2016, 25(2): 139-146.
41. He C, Peng C, Wang H, et al. The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults. Helicobacter, 2019, 24(4): e12590.
42. Jin D, Huang K, Xu M, et al. Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota. Gut Microbes, 2022, 14(1): 2120744.
43. Nascimento Araujo CD, Amorim AT, Barbosa MS, et al. Evaluating the presence of Mycoplasma hyorhinis, Fusobacterium nucleatum, and Helicobacter pylori in biopsies of patients with gastric cancer. Infect Agent Cancer, 2021, 16(1): 70.
44. He C, Peng C, Shu X, et al. Convergent dysbiosis of gastric mucosa and fluid microbiome during stomach carcinogenesis. Gastric Cancer, 2022, 25(5): 837-849.
45. Peng R, Liu S, You W, et al. Gastric microbiome alterations are associated with decreased CD8⁺ tissue-resident memory T cells in the tumor microenvironment of gastric cancer. Cancer Immunol Res, 2022, 10(10): 1224-1240.
46. Yang Y, Dai D, Jin W, et al. Microbiota and metabolites alterations in proximal and distal gastric cancer patients. J Transl Med, 2022, 20(1): 439.
47. Morgan AD, Seely KD, Hagenstein LD, et al. Bacterial involvement in progression and metastasis of adenocarcinoma of the stomach. Cancers (Basel), 2022, 14(19): 4886.
48. Hsieh YY, Tung SY, Pan HY, et al. Fusobacterium nucleatum colonization is associated with decreased survival of Helicobacter pylori-positive gastric cancer patients. World J Gastroenterol, 2021, 27(42): 7311-7323.

West China Medical Journal

Research progress of correlation between gastric cancer and non-Helicobacter pylori gastric microbes

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