Dysbiosis of the fecal microbiota in the TNBS-induced Crohn’s disease mouse model
Crohn’s disease (CD) is characterized by chronic transmural inflammation. The symptom of the mice model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) is closed to human under CD condition, so this kind of animal is widely used in the related researches. Although the dysbiosis of the fecal microbiota has been proved to play an important role in the patients with CD, the composition of the gastrointestinal microbiota in the mouse model under disease condition is still unclear. In the current study, male 7-week BALB/c mice were anesthetized and intrarectal administrated by ethanol (ET group), TNBS in ethanol (TN group), and phosphate buffered saline (PBS) (CK group) as control. The symptoms of individuals under the CD condition were observed, and the changes of the bacterial taxonomic structure and functional composition were revealed by next-generation sequencing (NGS) 16S sequencing. The BALB/c mice in TN group demonstrated CD-like symptoms and the damages in the intestinal tract. The NGS 16S results exhibited that the diversity and microbial composition under CD condition are significantly different with those in ET group. The KEGG Orthology (KO) profile were generated from PICRUSt, and function modules such as methanogenesis (M00347) and microcin C transport system (M00349) were found enriched in the individuals in the TN group. This study proved that mouse model induced by TNBS could develop the similar symptom to CD patient, and we firstly showed the significant intestinal microbe changes on both taxonomic structure and functional composition in this mouse model.
KeywordsInflammatory bowel disease Crohn’s disease TNBS-induced Fecal microbiome Mouse model
The study was supported by grants from National Nature Science Foundation of China (81470795), the Shenzhen Municipal Government of China (JSGG20140702161403250), the Shenzhen Engineering Laboratory of Detection and Intervention of human intestinal microbiome (DRC-SZ162), the Shenzhen Key Laboratory of Human commensal microorganisms and Health Research (CXB201108250098A), and the Shenzhen Municipal Government of China (the research and development of the novel personalized gut microbiota probiotic production, CXZZ20150330171521403).
Compliance with ethical standards
Animal experiments were performed in accordance with the guidelines of The Institutional Review Board on Bioethics and Biosafety of BGI (Number 13038).
Conflict of interest
The authors declare that they have no conflicts of interests.
- Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, Beiko RG, Huttenhower C (2013a) Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31:814–821CrossRefPubMedPubMedCentralGoogle Scholar
- Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, Beiko RG, Huttenhower C (2013b) Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31:814–821CrossRefPubMedPubMedCentralGoogle Scholar
- Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jørgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clément K, Doré J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T, MetaHIT consortium, Bork P, Wang J, Ehrlich SD, Pedersen O (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500:541–546CrossRefPubMedGoogle Scholar
- Loeuillard E, Bertrand J, Herranen A, Melchior C, Guérin C, Coëffier M, Aziz M, Déchelotte P, Savoye G, Marion-Letellier R (2014) 2,4,6-Trinitrobenzene sulfonic acid-induced chronic colitis with fibrosis and modulation of TGF-β1 signaling. World J Gastroenterol 20:18207–18215CrossRefPubMedPubMedCentralGoogle Scholar
- Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J, MetaHIT Consortium, Bork P, Ehrlich SD, Wang J (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65CrossRefPubMedPubMedCentralGoogle Scholar
- Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J (2012) A metagenome–wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60CrossRefPubMedGoogle Scholar
- Rath HC, Herfarth HH, Ikeda JS, Grenther WB, Hamm Jr TE, Balish E, Taurog JD, Hammer RE, Wilson KH, Sartor RB (1996) Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats. J Clin Invest 98:945–953CrossRefPubMedPubMedCentralGoogle Scholar
- Salonen A, Nikkilä J, Jalanka-Tuovinen J, Immonen O, Rajilić-Stojanović M, Kekkonen RA, Palva A, de Vos WM (2010) Comparative analysis of fecal DNA extraction methods with phylogenetic microarray: effective recovery of bacterial and archaeal DNA using mechanical cell analysis. J Microbiol Methods 81:127–134CrossRefPubMedGoogle Scholar
- Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF (2009) Introducing mothur: open–source, platform–independent, community–supported software for describing and comparing microbial communities. Appl Environ Microbiol 75:7537–7541CrossRefPubMedPubMedCentralGoogle Scholar