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Intestinal Microbiota Is Altered in Patients with Gastric Cancer from Shanxi Province, China

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Abstract

Background

Many diseases have been associated with intestinal microbial dysbiosis. Host–microbial interactions regulate immune function, which influences the development of gastric cancer.

Aims

The aims were to investigate the characteristics of intestinal microbiota composition in gastric cancer patients and correlations between the intestinal microbiota and cellular immunity.

Methods

Fecal samples were collected from 116 gastric cancer patients and 88 healthy controls from Shanxi Province, China. The intestinal microbiota was investigated by 16S rRNA gene sequencing. Peripheral blood samples were also collected from the 66 gastric cancer patients and 46 healthy controls. The populations of peripheral T lymphocyte subpopulations and NK cells were analyzed by flow cytometry.

Results

The intestinal microbiota in gastric cancer patients was characterized by increased species richness, decreased butyrate-producing bacteria, and the enrichment of other symbiotic bacteria, especially Lactobacillus, Escherichia, and Klebsiella. Lactobacillus and Lachnospira were key species in the network of gastric cancer-associated bacterial genera. The combination of the genera Lachnospira, Lactobacillus, Streptococcus, Veillonella, and Tyzzerella_3 showed good performance in distinguishing gastric cancer patients from healthy controls. There was no significant difference in enterotype distribution between healthy controls and gastric cancer patients. The percentage of CD3+ T cells was positively correlated with the abundance of Lactobacillus and Streptococcus, and CD3+ T cells, CD4+ T cells, and NK cells were associated with Lachnospiraceae taxa.

Conclusions

Our study revealed a dysbiotic intestinal microbiota in gastric cancer patients. The abundance of some intestinal bacterial genera was correlated with the population of peripheral immune cells.

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References

  1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–132.

    Article  PubMed  Google Scholar 

  2. Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, et al. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut. 2018;67:226–236.

    Article  CAS  PubMed  Google Scholar 

  3. Hibberd AA, Lyra A, Ouwehand AC, et al. Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ Open Gastroenterol. 2017;4:e145.

    Article  Google Scholar 

  4. Pushalkar S, Hundeyin M, Daley D, et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov. 2018;8:403–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhao L, Zhang F, Ding X, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359:1151–1156.

    Article  CAS  PubMed  Google Scholar 

  6. Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell. 2016;167:1469–1480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ticinesi A, Milani C, Guerra A, et al. Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers. Gut. 2018;2017:315–734.

    Google Scholar 

  8. Brown JM, Hazen SL. Microbial modulation of cardiovascular disease. Nat Rev Microbiol. 2018;16:171–181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Roy S, Trinchieri G. Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer. 2017;17:271–285.

    Article  CAS  PubMed  Google Scholar 

  10. **e YH, Gao QY, Cai GX, et al. Fecal Clostridium symbiosum for noninvasive detection of early and advanced colorectal cancer: test and validation studies. EBioMedicine. 2017;25:32–40.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dai Z, Coker OO, Nakatsu G, et al. Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers. Microbiome. 2018;6:70.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Geuking MB, Köller Y, Rupp S, McCoy KD. The interplay between the gut microbiota and the immune system. Gut Microbes. 2014;5:411–418.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Li K, Dan Z, Gesang L, et al. Comparative analysis of gut microbiota of native Tibetan and Han populations living at different altitudes. PLoS ONE. 2016;11:e155863.

    Google Scholar 

  14. Allali I, Boukhatem N, Bouguenouch L, et al. Gut microbiome of moroccan colorectal cancer patients. Med Microbiol Immunol. 2018;207:211–225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Costea PI, Hildebrand F, Arumugam M, et al. Enterotypes in the landscape of gut microbial community composition. Nat Microbiol. 2018;3:8–16.

    Article  CAS  PubMed  Google Scholar 

  16. Meehan CJ, Beiko RG. A phylogenomic view of ecological specialization in the Lachnospiraceae, a family of digestive tract-associated bacteria. Genome Biol Evol. 2014;6:703–713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhou L, Zhang M, Wang Y, et al. Faecalibacterium prausnitzii produces butyrate to maintain Th17/Treg balance and to ameliorate colorectal colitis by inhibiting histone deacetylase 1. Inflamm Bowel Dis. 2018;12:S110–S111.

    Google Scholar 

  18. McIntyre A, Gibson PR, Young GP. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut. 1993;34:386–391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Roy MJ, Dionne S, Marx G, et al. In vitro studies on the inhibition of colon cancer by butyrate and carnitine. Nutrition. 2009;25:1193–1201.

    Article  CAS  PubMed  Google Scholar 

  20. Perrin P, Cassagnau E, Burg C, et al. An interleukin 2/sodium butyrate combination as immunotherapy for rat colon cancer peritoneal carcinomatosis. Gastroenterology. 1994;107:1697–1708.

    Article  CAS  PubMed  Google Scholar 

  21. Berry D, Reinisch W. Intestinal microbiota: a source of novel biomarkers in inflammatory bowel diseases? Best Pract Res Clin Gastroenterol. 2013;27:47–58.

    Article  CAS  PubMed  Google Scholar 

  22. Dejea CM, Fathi P, Craig JM, et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018;359:592–597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang L, Zhou J, **n Y, et al. Bacterial overgrowth and diversification of microbiota in gastric cancer. Eur J Gastroenterol Hepatol. 2016;28:261–266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Aviles-Jimenez F, Vazquez-Jimenez F, Medrano-Guzman R, Mantilla A, Torres J. Stomach microbiota composition varies between patients with non-atrophic gastritis and patients with intestinal type of gastric cancer. Sci Rep. 2014;4:4202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrede JP. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci USA. 2010;107:11537–11542.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kaur CP, Vadivelu J, Chandramathi S. Impact of Klebsiella pneumoniae in lower gastrointestinal tract diseases. J Dig Dis. 2018;19:262–271.

    Article  PubMed  Google Scholar 

  27. Jo HJ, Kim J, Kim N, et al. Analysis of gastric microbiota by pyrosequencing: minor role of bacteria other than Helicobacter pylori in the gastric carcinogenesis. Helicobacter. 2016;21:364–374.

    Article  CAS  PubMed  Google Scholar 

  28. Coker OO, Dai Z, Nie Y, et al. Mucosal microbiome dysbiosis in gastric carcinogenesis. Gut. 2018;67:1024–1032.

    Article  CAS  PubMed  Google Scholar 

  29. Antharam VC, Li EC, Ishmael A, et al. Intestinal dysbiosis and depletion of butyrogenic bacteria in Clostridium difficile infection and nosocomial diarrhea. J Clin Microbiol. 2013;51:2884–2892.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65:749–756.

    Article  CAS  PubMed  Google Scholar 

  31. Imhann F, Bonder MJ, Vich VA, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740–748.

    Article  CAS  PubMed  Google Scholar 

  32. Gao F, Li M, Liu Y, Gao C, Wen S, Tang L. Intestinal dysbacteriosis induces changes of T lymphocyte subpopulations in Peyer’s patches of mice and orients the immune response towards humoral immunity. Gut Pathog. 2012;4:19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was funded by the National Natural Science Foundation of China (Grant Numbers: 81272696) and the Special Foundation for Talents of Shanxi Province of China (Grant Numbers: 201705D211021). We thank AJE (www.aje.com) for its linguistic assistance during the preparation of this manuscript.

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Correspondence to Wen Su.

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All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Electronic supplementary material

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10620_2018_5411_MOESM1_ESM.tif

Supplementary Figure 1. Rarefaction curves of the number of OTUs versus the number of reads. The x-axis shows the number of OTUs; the y-axis shows the number of reads sampled randomly. HC, healthy control group; GC, gastric cancer group, OTUs, operational taxonomic units (TIFF 3379 kb)

10620_2018_5411_MOESM2_ESM.tif

Supplementary Figure 2. The plots of the number of total OTUs (A) and the number of shared OTUs (B) versus the number of samples. HC, healthy control group; GC, gastric cancer group (TIFF 892 kb)

10620_2018_5411_MOESM3_ESM.tif

Supplementary Figure 3. Comparison of intestinal microbiota composition between healthy controls and gastric cancer patients in the sex-age-matched subset. Sob index (A) and Shannon index (B) at the OTU level in HC and GC. Principal coordinate analysis (PCoA) plots and analysis of similarity (ANOSIM) for (C) unweighted and (D) weighted UniFrac distances at the OTU level. (E) The most differentially abundant taxa between HC and GC by linear discriminant analysis (LDA) effect size (LEfSe) analysis. HC, healthy control group; GC, gastric cancer group (TIFF 4123 kb)

10620_2018_5411_MOESM4_ESM.tif

Supplementary Figure 4. The top 30 differentially abundant genera of bacteria between HC and GC by Wilcoxon rank-sum test. The left panel shows the average relative abundance of bacterial genera in both groups. The right panel shows 95% confidence intervals and P values. HC, healthy control group; GC, gastric cancer group (TIFF 2955 kb)

Supplementary material 5 (DOCX 18 kb)

Supplementary material 6 (DOCX 15 kb)

Supplementary material 7 (DOCX 14 kb)

Supplementary material 8 (DOCX 18 kb)

Supplementary material 9 (DOCX 16 kb)

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Qi, Yf., Sun, Jn., Ren, Lf. et al. Intestinal Microbiota Is Altered in Patients with Gastric Cancer from Shanxi Province, China. Dig Dis Sci 64, 1193–1203 (2019). https://doi.org/10.1007/s10620-018-5411-y

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  • DOI: https://doi.org/10.1007/s10620-018-5411-y

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