J Appl Biomed 19:1-13, 2021 | DOI: 10.32725/jab.2021.005

Gut microbial dysbiosis and its association with esophageal cancer

Hafiz Muhammad Ishaq1,2, Imran Shair Mohammad3, Kiran Sher Muhammad4, Huan Li5, Rao Zahid Abbas6, Zia ud Din Sindhu6, Shakir Ullah1, Yang Fan7, Abbas Sadiq8, Muhammad Asif Raza2, Riaz Hussain9, Hafiz Muhammad Arshad10, Iahtasham Khan11, Muhammad Umair Waqas2, Aziz Ul-Rahman2, Riffat Yasin2, Atif Rehman2, Rana Waseem Akhtar2, Jiru Xu1,*
1 University of Veterinary and Animal Sciences, Department of Clinical Sciences, Section of Epidemiology and public Health, Lahore Sub-campus Jhang, Pakistan
2 Muhammad Nawaz Shareef University of Agriculture Multan, Department of Veterinary and Animal Sciences, Multan, Pakistan
3 Sun Yat-sen University, University Town, School of Pharmaceutical Sciences, Guangzhou 510006, China
4 University of Agriculture, Department of Zoology Wild-life and Fisheries, Faisalabad, Pakistan
5 Xi'an Mental Health Centre, Xi'an, China
6 University of Agriculture Faisalabad-38040, Department of Parasitology, Faisalabad, Pakistan
7 Xinxiang Medical University, School of Basic Medical Science, Department of Microbiology, Xinxiang, China
8 Faculty of Veterinary and Animal Sciences Lahore, Department of Pathology, Lahore, Pakistan
9 Islamia University of Bahawalpur-63100, Faculty of Veterinary and Animal Sciences, Department of Pathology, Bahawalpur, Pakistan

Due to its aggressive nature and low survival rate, esophageal cancer is one of the deadliest cancer. While the intestinal microbiome significantly influences human health and disease. This research aimed to investigate and characterize the relative abundance of intestinal bacterial composition in esophageal cancer patients. The fecal samples were collected from esophageal cancer patients (n = 15) and healthy volunteers (n = 10). The PCR-DGGE was carried out by focusing on the V3 region of the 16S rRNA gene, and qPCR was performed for Bacteroides vulgatus, Escherichia coli, Bifidobacterium, Clostridium leptum and Lactobacillus. High-throughput sequencing of the 16S rRNA gene targeting the V3+V4 region was performed on 20 randomly selected samples. PCR-DGGE and High-throughput diversity results showed a significant alteration of gut bacterial composition between the experimental and control groups, which indicates the gut microbial dysbiosis in esophageal cancer patients. At the phylum level, there was significant enrichment of Bacteroidetes, while a non-significant decrease of Firmicutes in the experimental group. At family statistics, a significantly higher level of Bacteroidaceae and Enterobacteriaceae, while a significantly lower abundance of Prevotellaceae and Veillonellaceae were observed. There was a significantly high prevalence of genera Bacteroides, Escherichia-Shigella, while a significantly lower abundance of Prevotella_9 and Dialister in the experimental group as compared to the control group. Furthermore, the species analysis also showed significantly raised level of Bacteroides vulgatus and Escherichia coli in the experimental group. These findings revealed a significant gut microbial dysbiosis in esophageal cancer patients. So, the current study can be used for the understanding of esophageal cancer treatment, disease pathway, mechanism, and probiotic development.

Keywords: DGGE; Esophageal cancer; High-throughput sequencing; Intestinal dysbiosis; Microbiome
Grants and funding:

This study was supported by National Natural Science Foundation of China (No. 81730056).

Conflicts of interest:

All the authors declare no conflict of interests.

Received: June 8, 2020; Revised: January 17, 2021; Accepted: January 22, 2021; Prepublished online: February 3, 2021; Published: March 3, 2021  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Ishaq HM, Mohammad IS, Sher Muhammad K, Li H, Abbas RZ, Din Sindhu ZU, et al.. Gut microbial dysbiosis and its association with esophageal cancer. J Appl Biomed. 2021;19(1):1-13. doi: 10.32725/jab.2021.005. PubMed PMID: 34907711.
Download citation

References

  1. Amani J, Ahmadpour A, Imani Fooladi AA, Nazarian S (2015). Detection of E. coli O157:H7 and Shigella dysenteriae toxins in clinical samples by PCR-ELISA. Braz J Infect Dis 19: 278-284. DOI: 10.1016/j.bjid.2015.02.008. Go to original source... Go to PubMed...
  2. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. (2011). Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331: 337-341. DOI: 10.1126/science.1198469. Go to original source... Go to PubMed...
  3. Baba Y, Iwatsuki M, Yoshida N, Watanabe M, Baba H (2017). Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications. Ann Gastroenterol Surg 1: 99-104. DOI: 10.1002/ags3.12014. Go to original source... Go to PubMed...
  4. Baba Y, Watanabe M, Yoshida N, Kawanaka K, Yamashita Y, Baba H (2014). Radiofrequency ablation for pulmonary metastases from gastrointestinal cancers. Ann Thor Cardiovasc Surg 20: 99-105. DOI: 10.5761/atcs.ra.13-00343. Go to original source... Go to PubMed...
  5. Carmody RN, Turnbaugh PJ (2014). Host-microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics. J Clin Invest 124: 4173-4181. DOI: 10.1172/JCI72335. Go to original source... Go to PubMed...
  6. Chen J, Chia N, Kalari KR, Yao JZ, Novotna M, Soldan MMP, et al. (2016). Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Scientific Reports 6: 28484. DOI: 10.1038/srep28484. Go to original source... Go to PubMed...
  7. Dillon SM, Lee EJ, Kotter CV, Austin GL, Gianella S, Siewe B, et al. (2015). Gut Dendritic Cell Activation Links an AlteredColonic Microbiome to Mucosal and Systemic T Cell Activation in Untreated HIV-1 infection. Mucosal Immunol 9: 24-37. DOI: 10.1038/mi.2015.33. Go to original source... Go to PubMed...
  8. Garrett WS (2015). Cancer and the microbiota. Science 348: 80-86. DOI: 10.1126/science.aaa4972. Go to original source... Go to PubMed...
  9. Guarner F, Malagelada J-R (2003). Gut flora in health and disease. Lancet 361: 512-519. DOI: 10.1016/S0140-6736(03)12489-0. Go to original source... Go to PubMed...
  10. Hameed A, Ijaz S, Mohammad IS, Muhammad KS, Akhtar N, Khan HMS (2017). Aglycone solanidine and solasodine derivatives: A natural approach towards cancer. Biomed Pharmacother 94: 446-457. DOI: 10.1016/j.biopha.2017.07.147. Go to original source... Go to PubMed...
  11. Huang F-L, Yu S-J (2018). Esophageal cancer: Risk factors, genetic association, and treatment. Asian J Surg 41: 210-215. DOI: 10.1016/j.asjsur.2016.10.005. Go to original source... Go to PubMed...
  12. Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, et al. (2013). Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342: 967-970. DOI: 10.1126/science.1240527. Go to original source... Go to PubMed...
  13. Ishaq HM, Mohammad IS, Guo H, Shahzad M, Hou YJ, Ma C, et al. (2017a). Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients. Biomed Pharmacother 95: 865-874. DOI: 10.1016/j.biopha.2017.08.101. Go to original source... Go to PubMed...
  14. Ishaq HM, Mohammad IS, Shahzad M, Ma C, Raza MA, Wu X, et al. (2018a). Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients. Int J Biol Sci 14: 1558-1570. DOI: 10.7150/ijbs.24151. Go to original source... Go to PubMed...
  15. Ishaq HM, Shahzad M, Wu X, Ma C, Xu J (2017b). Molecular Characterization Of Fecal Microbiota Of Healthy Chinese Tobacco Smoker Subjects In Shaanxi Province, Xi'an China. J Ayub Med Coll Abbottabad 29: 3-7. Go to PubMed...
  16. Ishaq HM, Shahzad M, Wu X, Ma C, Xu J (2018b). Gut Microbe Analysis between Asthma Patients and Healthy Volunteers in Shaanxi Province, Xi'an, China. Pakistan Journal of Zoology 50(1). DOI: 10.17582/journal.pjz/2018.50.1.165.173. Go to original source...
  17. Kang D-W, Jin GP, Ilhan ZE, Wallstrom G, Labaer J, Adams JB, Krajmalnik-Brown R (2013). Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children. PloS One 8: e68322. DOI: 10.1371/journal.pone.0068322. Go to original source... Go to PubMed...
  18. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vader F, Arora T, et al. (2015). Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella. Cell Metabolism 22: 971-982. DOI: 10.1016/j.cmet.2015.10.001. Go to original source... Go to PubMed...
  19. Ma C, Wu X, Nawaz M, Li J, Yu P, Moore JE, Xu J (2011). Molecular characterization of fecal microbiota in patients with viral diarrhea. Curr Microbiol 63: 259-266. DOI: 10.1007/s00284-011-9972-7. Go to original source... Go to PubMed...
  20. Manichanh C, Varela E, Martinez C, Antolin M, Llopis M, Doré J, et al. (2008). The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea. Am J Gastroenterol 103: 1754-1761. DOI: 10.1111/j.1572-0241.2008.01868.x. Go to original source... Go to PubMed...
  21. Mao A (2016). Interventional Therapy of Esophageal Cancer. Gastrointest Tumors 3: 59-68. DOI: 10.1159/000447512. Go to original source... Go to PubMed...
  22. Mohammad IS, Chaurasiya B, Yang X, Lin C, Rong H, He W (2020a). Homotype-Targeted Biogenic Nanoparticles to Kill Multidrug-Resistant Cancer Cells. Pharmaceutics 12: 950. DOI: 10.3390/pharmaceutics12100950. Go to original source... Go to PubMed...
  23. Mohammad IS, He W, Yin L (2018a). A smart paclitaxel-disulfiram nanococrystals for efficient MDR reversal and enhanced apoptosis. Pharm Res 35: 77. DOI: 10.1007/s11095-018-2370-0. Go to original source... Go to PubMed...
  24. Mohammad IS, He W, Yin L (2018b). Understanding of human ATP binding cassette superfamily and novel multidrug resistance modulators to overcome MDR. Biomed Pharmacother 100: 335-348. DOI: 10.1016/j.biopha.2018.02.038. Go to original source... Go to PubMed...
  25. Mohammad IS, He W, Yin L (2020b). Insight on Multidrug Resistance and Nanomedicine Approaches to Overcome MDR. Crit Rev Ther Drug Carrier Syst 37: 473-509. DOI: 10.1615/CritRevTherDrugCarrierSyst.2020025052. Go to original source... Go to PubMed...
  26. Mulvey MA, Schilling JD, Martinez JJ, Hultgren SJ (2000). Bad bugs and beleaguered bladders: Interplay between uropathogenic Escherichia coli and innate host defenses. Proc Natl Acad Sci U S A 97: 8829-8835. DOI: 10.1073/pnas.97.16.8829. Go to original source... Go to PubMed...
  27. Nam Y-D, Kim HJ, Seo J-G, Kang SW, Bae J-W (2013). Impact of Pelvic Radiotherapy on Gut Microbiota of Gynecological Cancer Patients Revealed by Massive Pyrosequencing. PloS One 8: e82659. DOI: 10.1371/journal.pone.0082659. Go to original source... Go to PubMed...
  28. Pittayanon R, Lau JT, Yuan Y, Leontiadis GI, Tse F, Surette M, Moayyedi P (2019). Gut microbiota in patients with irritable bowel syndrome - a systematic review. Gastroenterology 157: 97-108. DOI: 10.1053/j.gastro.2019.03.049. Go to original source... Go to PubMed...
  29. Power SE, O'Toole PW, Stanton C, Ross RP, Fitzgerald GF (2013). Intestinal microbiota, diet and health. Br J Nutr 111: 387-402. DOI: 10.1017/S0007114513002560. Go to original source... Go to PubMed...
  30. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464: 59-65. DOI: 10.1038/nature08821. Go to original source... Go to PubMed...
  31. Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, et al. (2017). New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 5: 24. DOI: 10.1186/s40168-017-0242-1. Go to original source... Go to PubMed...
  32. The Cancer Genome Atlas Research Network (2017). Integrated genomic characterization of oesophageal carcinoma. Nature 541: 169-175. DOI: 10.1038/nature20805. Go to original source... Go to PubMed...
  33. Triboulet J-P, Mariette C (2008). Oesophageal cancer: what's new during the last 10 years? Bulletin du Cancer 95: 425-431. DOI: 10.1684/bdc.2008.0626. Go to original source... Go to PubMed...
  34. Van Der Gucht K, Sabbe K, De Meester L, Vloemans N, Zwart G, Gillis M, Vyverman W (2001). Contrasting bacterioplankton community composition and seasonal dynamics in two neighbouring hypertrophic freshwater lakes. Environ Microbiol 3: 680-690. DOI: 10.1046/j.1462-2920.2001.00242.x. Go to original source... Go to PubMed...
  35. Walsh CJ, Guinane CM, O'Toole PW, Cotter PD (2014). Beneficial modulation of the gut microbiota. FEBS Lett 588: 4120-4130. DOI: 10.1016/j.febslet.2014.03.035. Go to original source... Go to PubMed...
  36. Walters WA, Xu Z, Knight R (2014). Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett 588: 4223-4233. DOI: 10.1016/j.febslet.2014.09.039. Go to original source... Go to PubMed...
  37. Wang Y, Luo X, Mao X, Tao Y, Ran X, Zhao H, Xiong J, Li L (2017). Gut microbiome analysis of type 2 diabetic patients from the Chinese minority ethnic groups the Uygurs and Kazaks. PLoS One 12: e0172774. DOI: 10.1371/journal.pone.0172774. Go to original source... Go to PubMed...
  38. Wu X, Ma C, Han L, Nawaz M, Gao F, Zhang X, et al. (2010). Molecular characterization of the faecal microbiota in patients with type II diabetes. Curr Microbiol 61: 69-78. DOI: 10.1007/s00284-010-9582-9. Go to original source... Go to PubMed...
  39. Zaidi AH, Kelly LA, Kreft RE, Barlek M, Omstead AN, Matsui D, et al. (2016). Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma. BMC Cancer 16: 52. DOI: 10.1186/s12885-016-2093-8. Go to original source... Go to PubMed...
  40. Zhang M, Zheng M, Wu Z, Guan M, Liu S, Zhao W, Cheng J (2017). Alteration of the gut microbial community after N,N-Dimethylformamide exposure. J Toxicol Sci 42: 241-250. DOI: 10.2131/jts.42.241. Go to original source... Go to PubMed...
  41. Zhou L, Li X, Ahmed A, Wu D, Liu L, Qiu J, et al. (2014). Gut microbe analysis between hyperthyroid and healthy individuals. Curr Microbiol 69: 675-680. DOI: 10.1007/s00284-014-0640-6. Go to original source... Go to PubMed...

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.