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26.07.2016 | Original Article

Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma

verfasst von: Akinari Sawada, Yasuhiro Fujiwara, Yasuaki Nagami, Fumio Tanaka, Hirokazu Yamagami, Tetsuya Tanigawa, Masatsugu Shiba, Kazunari Tominaga, Toshio Watanabe, Min Gi, Hideki Wanibuchi, Tetsuo Arakawa

Erschienen in: Digestive Diseases and Sciences | Ausgabe 11/2016

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Abstract

Background

Recent studies suggest that chronic inflammation-associated cancer is relevant to microbiome. Esophageal adenocarcinoma arises from an inflammatory condition called Barrett’s esophagus, which is caused by gastroesophageal reflux. We hypothesized that esophageal microbiome plays a role in carcinogenesis of esophageal adenocarcinoma.

Aim

We investigated whether alteration of microbiome using antibiotics affects the development of esophageal adenocarcinoma in a rat model.

Methods

Seven-week-old male Wistar rats which had undergone esophagojejunostomy were divided into control (n = 21) and antibiotic groups (n = 22) at 21 weeks after surgery. Control animals were given drinking water, while the other group was given penicillin G and streptomycin in drinking water until rats were killed at 40 weeks after operation. Incidence rates of Barrett’s esophagus and adenocarcinoma in each group were evaluated by histological analysis. DNA was extracted from a portion of the distal esophagus, and the microbiome was investigated using terminal restriction fragment length polymorphism (T-RFLP) analysis.

Results

All rats in both groups developed Barrett’s esophagus. Incidence of esophageal adenocarcinoma was similar between both groups with a trend to reduced incidence in the antibiotics group (89 % in the control group, 71 % in the antibiotics group, P = 0.365). T-RFLP analysis showed that esophageal microbiome was different between two groups such as the proportion of Lactobacillales was lower in the antibiotics group and Clostridium cluster XIVa and XVIII was higher in the antibiotics group.

Conclusions

Alteration of microbiome does not affect the incidence of esophageal adenocarcinoma. Microbiome may not contribute to the development of esophageal adenocarcinoma.

Rubenstein JH, Shaheen NJ. Epidemiology, diagnosis, and management of esophageal adenocarcinoma. Gastroenterology. 2015;149:302.e1–317.e1.

Spechler SJ. Barrett esophagus and risk of esophageal cancer: a clinical review. JAMA. 2013;310:627–636.CrossRefPubMed

Paulson TG, Reid BJ. Focus on Barrett’s esophagus and esophageal adenocarcinoma. Cancer Cell. 2004;6:11–16.CrossRefPubMed

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;13:759–771.CrossRefPubMed

Arthur JC, Perez-Chanona E, Muhlbauer M, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012;338:120–123.CrossRefPubMedPubMedCentral

Honda K, Littman DR. The microbiome in infectious disease and inflammation. Annu Rev Immunol. 2012;30:759–795.CrossRefPubMedPubMedCentral

Guo W, Ding J, Huang Q, Jerrells T, Deitch EA. Alterations in intestinal bacterial flora modulate the systemic cytokine response to hemorrhagic shock. Am J Physiol. 1995;269:G827–G832.PubMed

Yoshimoto S, Loo TM, Atarashi K, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499:97–101.CrossRefPubMed

Miwa K, Sahara H, Segawa M, et al. Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in rats. Int J Cancer. 1996;67:269–274.CrossRefPubMed

10.

Miyashita T, Miwa K, Fujimura T, et al. The severity of duodeno-esophageal reflux influences the development of different histological types of esophageal cancer in a rat model. Int J Cancer. 2013;132:1496–1504.CrossRefPubMed

11.

Shen XJ, Rawls JF, Randall T, et al. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes. 2010;1:138–147.CrossRefPubMedPubMedCentral

12.

Takahashi S, Tomita J, Nishioka K, Hisada T, Nishijima M. Development of a prokaryotic universal primer for simultaneous analysis of bacteria and archaea using next-generation sequencing. PLoS One. 2014;9:e105592.CrossRefPubMedPubMedCentral

13.

Muyzer G, de Waal EC, Uitterlinden AG. Profiling of complex microbial populations by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA. Appl Environ Microbiol. 1993;59:695–700.PubMedPubMedCentral

14.

Nagashima K, Hisada T, Sato M, Mochizuki J. Application of new primer-enzyme combinations to terminal restriction fragment length polymorphism profiling of bacterial populations in human feces. Appl Environ Microbiol. 2003;69:1251–1262.CrossRefPubMedPubMedCentral

15.

Pei Z, Bini EJ, Yang L, Zhou M, Francois F, Blaser MJ. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci USA. 2004;101:4250–4255.CrossRefPubMedPubMedCentral

16.

Pei Z, Yang L, Peek RM Jr, Levine SM, Pride DT, Blaser MJ. Bacterial biota in reflux esophagitis and Barrett’s esophagus. World J Gastroenterol. 2005;11:7277–7283.CrossRefPubMedPubMedCentral

17.

Yang L, Lu X, Nossa CW, Francois F, Peek RM, Pei Z. Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. Gastroenterology. 2009;137:588–597.CrossRefPubMedPubMedCentral

18.

Liu N, Ando T, Ishiguro K, et al. Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett’s esophagus. BMC Infect Dis. 2013;13:130.CrossRefPubMedPubMedCentral

19.

Fan YP, Chakder S, Gao F, Rattan S. Inducible and neuronal nitric oxide synthase involvement in lipopolysaccharide-induced sphincteric dysfunction. Am J Physiol Gastrointest Liver Physiol. 2001;280:G32–G42.PubMed

20.

Yang L, Francois F, Pei Z. Molecular pathways: pathogenesis and clinical implications of microbiome alteration in esophagitis and Barrett esophagus. Clin Cancer Res. 2012;18:2138–2144.CrossRefPubMedPubMedCentral

21.

Colleypriest BJ, Ward SG, Tosh D. How does inflammation cause Barrett’s metaplasia? Curr Opin Pharmacol. 2009;9:721–726.CrossRefPubMed

22.

Lee JS, Oh TY, Ahn BO, et al. Involvement of oxidative stress in experimentally induced reflux esophagitis and Barrett’s esophagus: clue for the chemoprevention of esophageal carcinoma by antioxidants. Mutat Res. 2001;480–481:189–200.CrossRefPubMed

23.

Konturek PC, Nikiforuk A, Kania J, Raithel M, Hahn EG, Muhldorfer S. Activation of NFkappaB represents the central event in the neoplastic progression associated with Barrett’s esophagus: a possible link to the inflammation and overexpression of COX-2, PPARγ and growth factors. Dig Dis Sci. 2004;49:1075–1083.CrossRefPubMed

24.

O’Riordan JM, Abdel-latif MM, Ravi N, et al. Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation–metaplasia–dysplasia–adenocarcinoma sequence in the esophagus. Am J Gastroenterol. 2005;100:1257–1264.CrossRefPubMed

25.

Abdel-Latif MM, Kelleher D, Reynolds JV. Potential role of NF-kappaB in esophageal adenocarcinoma: as an emerging molecular target. J Surg Res. 2009;153:172–180.CrossRefPubMed

26.

Kohata Y, Nakahara K, Tanigawa T, et al. Rebamipide alters the esophageal microbiome and reduces the incidence of Barrett’s esophagus in a rat model. Dig Dis Sci. 2015;60:2654–2661.CrossRefPubMed

27.

Dapito DH, Mencin A, Gwak GY, et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell. 2012;21:504–516.CrossRefPubMedPubMedCentral

28.

Polk DB, Peek RM Jr. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010;10:403–414.CrossRefPubMedPubMedCentral

29.

Prorok-Hamon M, Friswell MK, Alswied A, et al. Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer. Gut. 2014;63:761–770.CrossRefPubMed

30.

Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292–298.CrossRefPubMedPubMedCentral

31.

Blackett KL, Siddhi SS, Cleary S, et al. Oesophageal bacterial biofilm changes in gastro-oesophageal reflux disease, Barrett’s and oesophageal carcinoma: association or causality? Aliment Pharmacol Ther. 2013;37:1084–1092.CrossRefPubMed

32.

Zaidi AH, Kelly LA, Kreft RE, et al. Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma. BMC Cancer. 2015;16:52.CrossRef

33.

Garcia JM, Splenser AE, Kramer J, et al. Circulating inflammatory cytokines and adipokines are associated with increased risk of Barrett’s esophagus: a case–control study. Clin Gastroenterol Hepatol. 2014;12:229.e3–238.e3.CrossRef

34.

Siahpush SH, Vaughan TL, Lampe JN, et al. Longitudinal study of insulin-like growth factor, insulin-like growth factor binding protein-3, and their polymorphisms: risk of neoplastic progression in Barrett’s esophagus. Cancer Epidemiol Biomark Prev. 2007;16:2387–2395.CrossRef

35.

Cho I, Yamanishi S, Cox L, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488:621–626.CrossRefPubMedPubMedCentral

Titel: Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma
verfasst von: Akinari Sawada
Yasuhiro Fujiwara
Yasuaki Nagami
Fumio Tanaka
Hirokazu Yamagami
Tetsuya Tanigawa
Masatsugu Shiba
Kazunari Tominaga
Toshio Watanabe
Min Gi
Hideki Wanibuchi
Tetsuo Arakawa
Publikationsdatum: 26.07.2016
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 11/2016
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-016-4263-6

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Alteration of Esophageal Microbiome by Antibiotic Treatment Does Not Affect Incidence of Rat Esophageal Adenocarcinoma