Please wait a minute...
购物车 申请加入邮件组 English
高级检索 图表检索
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

热点文章  |  下载排行  |  浏览排行
在线投稿 免费RSS订阅
Frontiers of Medicine  2019, Vol. 13 Issue (4): 461-470   https://doi.org/10.1007/s11684-019-0695-7
  本期目录
Altered intestinal microbiota associated with colorectal cancer
Hong Zhang1, Ying Chang2, Qingqing Zheng2, Rong Zhang1, Cheng Hu1(), Weiping Jia1
1. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
2. Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
 全文: PDF(692 KB)   HTML
Abstract：

The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal--luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.
Key words： colorectal cancer (CRC)    gut microbiota    intestinal    Eubacterium    Devosia
收稿日期: 2018-04-15      出版日期: 2019-08-02
Corresponding Author(s): Cheng Hu   
 引用本文:   
. [J]. Frontiers of Medicine, 2019, 13(4): 461-470.
Hong Zhang, Ying Chang, Qingqing Zheng, Rong Zhang, Cheng Hu, Weiping Jia. Altered intestinal microbiota associated with colorectal cancer. Front. Med., 2019, 13(4): 461-470.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-019-0695-7
https://academic.hep.com.cn/fmd/CN/Y2019/V13/I4/461
　 NG (n = 14) CG (n = 9) P value
Male/female 7/7 6/3 0.6693
Age (year), mean±SD 44.1±15 62.6±8.9 0.0041
BMI (kg/m2), mean±SD 22.03±2.68 22.37±2.17 0.7527
Family history of CRC, % 0 22.2 0.0001
Tab.1  
Fig.1  
Fig.2  
Group enriched Taxonomic rank Bacteria NG (%) CG (%) P value
CG Genus Devosia 0.006 (0.003–0.010) 0.023 (0.009–0.029) 0.008
Family Hyphomicrobiaceae 0.006 (0.003–0.010) 0.023 (0.009–0.029) 0.008
Order Rhizobiales 0.008 (0.003–0.012) 0.027 (0.019–0.034) 0.012
Class Alphaproteobacteria 0.010 (0.006–0.017) 0.031 (0.027–0.039) 0.020
NG Species stercorea 0.063 (0.042–0.138) 0.004 (0–0.035) 0.001
Species copri 0.126 (0.051–0.993) 0.009 (0.004–0.115) 0.006
Family Prevotellaceae 0.225 (0.172–1.310) 0.042 (0.023–0.170) 0.006
Genus Eubacterium 0.025 (0.016–0.123) 0.005 (0–0.017) 0.009
Genus Klebsiella 0.020 (0.010–0.090) 0.008 (0.005-0.012) 0.014
Order Desulfovibrionales 0.127 (0.049–0.441) 0.037 (0.021–0.104) 0.014
Class Deltaproteobacteria 0.127 (0.049–0.446) 0.037 (0.025–0.104) 0.017
Family Desulfovibrionaceae 0.126 (0.045–0.368) 0.037 (0.017–0.104) 0.017
Genus 02d06 0.044 (0.015–0.074) 0.009 (0–0.025) 0.018
Species producta 0.189 (0.033–0.287) 0.014 (0.008–0.059) 0.023
Genus Phascolarctobacterium 0.062 (0.005–0.125) 0.005 (0–0.014) 0.027
Family Clostridiaceae 0.269 (0.164–0.843) 0.122 (0.033–0.182) 0.038
　 Genus Leptotrichia 0.028 (0.021–0.132) 0.010 (0.005–0.016) 0.038
Tab.2  
Fig.3  
KEGG pathways NG CG P value
Cancers 　 　 　
Small cell lung cancer 0.10 (0.07–0.18) 0.30 (0.13–0.40) 0.016
Colorectal cancer 0.10 (0.07–0.18) 0.30 (0.13–0.40) 0.017
Bladder cancer 30.26 (11.85–69.91) 42.23 (29.89–109.37) 0.441
Renal cell carcinoma 55.01 (22.16–123.0) 69.56 (37.40–201.82) 0.443
Infectious diseases 　 　 　
Vibrio cholerae infection 0.90 (0.54–3.02) 0.57 (0.37–0.79) 0.005
Influenza A 0.10 (0.07–0.18) 0.30 (0.13–0.40) 0.016
Toxoplasmosis 0.10 (0.07–0.18) 0.30 (0.13–0.40) 0.016
Pertussis 541.81 (190.97–942.52) 596.60 (481.92–1893.19) 0.256
African trypanosomiasis 37.04 (20.87–72.41) 43.24 (32.99–109.60) 0.400
Chagas disease (American trypanosomiasis) 31.72 (20.66–72.18) 43.15 (32.76–109.52) 0.403
Cardiovascular diseases 　 　 　
Viral myocarditis 0.10 (0.07–0.18) 0.30 (0.13–0.40) 0.016
Cell growth and death 　 　 　
p53 signaling pathway 0.10 (0.07–0.18) 0.30 (0.13–0.40) 0.016
Meiosis-yeast 5.88 (2.38–8.91) 1.77 (1.17–5.87) 0.088
Apoptosis 1.79 (1.56–2.06) 2.27 (0.82–6.38) 0.295
Transport and catabolism 　 　 　
Endocytosis 0 0.04 (0–0.05) 0.044
Lysosome 621.65 (352.94–720.52) 428.15 (241.70–638.47) 0.282
Biosynthesis of other secondary metabolites 　 　 　
Stilbenoid, diarylheptanoid, and gingerol biosynthesis 3.89 (1.75–5.86) 3.67 (1.58–6.24) 0.085
Betalain biosynthesis 0.06 (0.03–0.14) 0.05 (0.02–0.24) 0.199
Butirosin and neomycin biosynthesis 601.70 (441.17–668.97) 356.68 (328.17–538.20) 0.451
Flavonoid biosynthesis 26.09 (22.30–43.97) 24.90 (10.00–35.72) 0.485
Endocrine system 　 　 　
GnRH signaling pathway 0 0.04 (0–0.05) 0.043
Melanogenesis 0.01 (0–0.05) 0.03 (0–0.12) 0.061
Proximal tubule bicarbonate reclamation 124.57 (83.98–164.06) 101.69 (95.73–231.88) 0.453
Immune system 　 　 　
FcγR-mediated phagocytosis 0 0.04 (0–0.05) 0.043
RIG-I-like receptor signaling pathway 30.90 (13.48–42.25) 14.64 (7.41–26.66) 0.065
Tab.3  
1 D Cunningham, W Atkin, HJ Lenz, HT Lynch, B Minsky, B Nordlinger, N Starling. Colorectal cancer. Lancet 2010; 375(9719): 1030–1047
https://doi.org/10.1016/S0140-6736(10)60353-4 pmid: 20304247
2 J Regula, M Rupinski, E Kraszewska, M Polkowski, J Pachlewski, J Orlowska, MP Nowacki, E Butruk. Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia. N Engl J Med 2006; 355(18): 1863–1872
https://doi.org/10.1056/NEJMoa054967 pmid: 17079760
3 MA Azcárate-Peril, M Sikes, JM Bruno-Bárcena. The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer? Am J Physiol Gastrointest Liver Physiol 2011; 301(3): G401–G424
https://doi.org/10.1152/ajpgi.00110.2011 pmid: 21700901
4 Y Horiuchi, J Fujisaki, N Ishizuka, M Omae, A Ishiyama, T Yoshio, T Hirasawa, Y Yamamoto, M Nagahama, H Takahashi, T Tsuchida. Study on clinical factors involved in Helicobacter pylori-uninfected, undifferentiated-type early gastric cancer. Digestion 2017; 96(4): 213–219
https://doi.org/10.1159/000481817 pmid: 29050004
5 JK Nicholson, E Holmes, J Kinross, R Burcelin, G Gibson, W Jia, S Pettersson. Host-gut microbiota metabolic interactions. Science 2012; 336(6086): 1262–1267
https://doi.org/10.1126/science.1223813 pmid: 22674330
6 T Yatsunenko, FE Rey, MJ Manary, I Trehan, MG Dominguez-Bello, M Contreras, M Magris, G Hidalgo, RN Baldassano, AP Anokhin, AC Heath, B Warner, J Reeder, J Kuczynski, JG Caporaso, CA Lozupone, C Lauber, JC Clemente, D Knights, R Knight, JI Gordon. Human gut microbiome viewed across age and geography. Nature 2012; 486(7402): 222–227
https://doi.org/10.1038/nature11053 pmid: 22699611
7 DM Parkin. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118(12): 3030–3044
https://doi.org/10.1002/ijc.21731 pmid: 16404738
8 EL Amitay, S Werner, M Vital, DH Pieper, D Höfler, IJ Gierse, J Butt, Y Balavarca, K Cuk, H Brenner. Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study. Carcinogenesis 2017; 38(8): 781–788
https://doi.org/10.1093/carcin/bgx053 pmid: 28582482
9 Y Yamaoka, Y Suehiro, S Hashimoto, T Hoshida, M Fujimoto, M Watanabe, D Imanaga, K Sakai, T Matsumoto, M Nishioka, T Takami, N Suzuki, S Hazama, H Nagano, I Sakaida, T Yamasaki. Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population. J Gastroenterol 2018; 53(4): 517–524
pmid: 28823057
10 J Repass, N Maherali, K, Owen Reproducibility Project: Cancer Biology. Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. eLife 2016; 5:e10012
https://doi.org/DOI:10.7554/eLife.10012 pmid: 26882501
11 L Mira-Pascual, R Cabrera-Rubio, S Ocon, P Costales, A Parra, A Suarez, F Moris, L Rodrigo, A Mira, MC Collado. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol 2015; 50(2): 167–179
https://doi.org/10.1007/s00535-014-0963-x pmid: 24811328
12 W Mottawea, CK Chiang, M Mühlbauer, AE Starr, J Butcher, T Abujamel, SA Deeke, A Brandel, H Zhou, S Shokralla, M Hajibabaei, R Singleton, EI Benchimol, C Jobin, DR Mack, D Figeys, A Stintzi. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn’s disease. Nat Commun 2016; 7(1): 13419
https://doi.org/10.1038/ncomms13419 pmid: 27876802
13 C Quast, E Pruesse, P Yilmaz, J Gerken, T Schweer, P Yarza, J Peplies, FO Glöckner. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 2013; 41(Database issue): D590–D596
pmid: 23193283
14 PD Schloss, SL Westcott, T Ryabin, JR Hall, M Hartmann, EB Hollister, RA Lesniewski, BB Oakley, DH Parks, CJ Robinson, JW Sahl, B Stres, GG Thallinger, DJ Van Horn, CF Weber. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 2009; 75(23): 7537–7541
https://doi.org/10.1128/AEM.01541-09 pmid: 19801464
15 N Segata, J Izard, L Waldron, D Gevers, L Miropolsky, WS Garrett, C Huttenhower. Metagenomic biomarker discovery and explanation. Genome Biol 2011; 12(6): R60
https://doi.org/10.1186/gb-2011-12-6-r60 pmid: 21702898
16 MG Langille, J Zaneveld, JG Caporaso, D McDonald, D Knights, JA Reyes, JC Clemente, DE Burkepile, RL Vega Thurber, R Knight, RG Beiko, C Huttenhower. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 2013; 31(9): 814–821
https://doi.org/10.1038/nbt.2676 pmid: 23975157
17 RE Ley, DA Peterson, JI Gordon. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006; 124(4): 837–848
https://doi.org/10.1016/j.cell.2006.02.017 pmid: 16497592
18 K Kimura, AL McCartney, MA McConnell, GW Tannock. Analysis of fecal populations of bifidobacteria and lactobacilli and investigation of the immunological responses of their human hosts to the predominant strains. Appl Environ Microbiol 1997; 63(9): 3394–3398
pmid: 9292990
19 CL Sears. A dynamic partnership: celebrating our gut flora. Anaerobe 2005; 11(5): 247–251
https://doi.org/10.1016/j.anaerobe.2005.05.001 pmid: 16701579
20 Q Zhu, Z Jin, W Wu, R Gao, B Guo, Z Gao, Y Yang, H Qin. Analysis of the intestinal lumen microbiota in an animal model of colorectal cancer. PLoS One 2014; 9(6): e90849
https://doi.org/10.1371/journal.pone.0090849 pmid: 24603888
21 T Wang, G Cai, Y Qiu, N Fei, M Zhang, X Pang, W Jia, S Cai, L Zhao. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 2012; 6(2): 320–329
https://doi.org/10.1038/ismej.2011.109 pmid: 21850056
22 T Tahara, E Yamamoto, H Suzuki, R Maruyama, W Chung, J Garriga, J Jelinek, HO Yamano, T Sugai, B An, I Shureiqi, M Toyota, Y Kondo, MR Estécio, JP Issa. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 2014; 74(5): 1311–1318
https://doi.org/10.1158/0008-5472.CAN-13-1865 pmid: 24385213
23 AN McCoy, F Araújo-Pérez, A Azcárate-Peril, JJ Yeh, RS Sandler, TO Keku. Fusobacterium is associated with colorectal adenomas. PLoS One 2013; 8(1): e53653
https://doi.org/10.1371/journal.pone.0053653 pmid: 23335968
24 PD Scanlan, F Shanahan, Y Clune, JK Collins, GC O’Sullivan, M O’Riordan, E Holmes, Y Wang, JR Marchesi. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol 2008; 10(3): 789–798
https://doi.org/10.1111/j.1462-2920.2007.01503.x pmid: 18237311
25 T Sasada, T Hinoi, Y Saito, T Adachi, Y Takakura, Y Kawaguchi, Y Sotomaru, K Sentani, N Oue, W Yasui, H Ohdan. Chlorinated water modulates the development of colorectal tumors with chromosomal instability and gut microbiota in APC-deficient mice. PLoS One 2015; 10(7): e0132435
https://doi.org/10.1371/journal.pone.0132435 pmid: 26186212
26 PJ Turnbaugh, RE Ley, MA Mahowald, V Magrini, ER Mardis, JI Gordon. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444(7122): 1027–1031
https://doi.org/10.1038/nature05414 pmid: 17183312
27 D Scharlau, A Borowicki, N Habermann, T Hofmann, S Klenow, C Miene, U Munjal, K Stein, M Glei. Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res 2009; 682(1): 39–53
https://doi.org/10.1016/j.mrrev.2009.04.001 pmid: 19383551
28 R Balamurugan, E Rajendiran, S George, GV Samuel, BS Ramakrishna. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol 2008; 23(8 Pt 1): 1298–1303
https://doi.org/10.1111/j.1440-1746.2008.05490.x pmid: 18624900
29 RK Le Leu, JM Winter, CT Christophersen, GP Young, KJ Humphreys, Y Hu, SW Gratz, RB Miller, DL Topping, AR Bird, MA Conlon. Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial. Br J Nutr 2015; 114(2): 220–230
https://doi.org/10.1017/S0007114515001750 pmid: 26084032
30 SH Duncan, A Belenguer, G Holtrop, AM Johnstone, HJ Flint, GE Lobley. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol 2007; 73(4): 1073–1078
https://doi.org/10.1128/AEM.02340-06 pmid: 17189447
31 S Sengupta, JG Muir, PR Gibson. Does butyrate protect from colorectal cancer? J Gastroenterol Hepatol 2006; 21(1 Pt 2): 209–218
https://doi.org/10.1111/j.1440-1746.2006.04213.x pmid: 16460475
32 I Sato, M Ito, M Ishizaka, Y Ikunaga, Y Sato, S Yoshida, M Koitabashi, S Tsushima. Thirteen novel deoxynivalenol-degrading bacteria are classified within two genera with distinct degradation mechanisms. FEMS Microbiol Lett 2012; 327(2): 110–117
https://doi.org/10.1111/j.1574-6968.2011.02461.x pmid: 22098388
[1] FMD-19004-OF-HC_suppl_1 Download
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed