Cigarette smoke promotes colorectal cancer through modulation of gut microbiota and related metabolites

被引:194
作者
Bai, Xiaowu [1 ,2 ,3 ]
Wei, Hong [4 ]
Liu, Weixin [1 ,2 ]
Coker, Olabisi Oluwabukola [1 ,2 ]
Gou, Hongyan [1 ,2 ]
Liu, Changan [1 ,2 ]
Zhao, Liuyang [1 ,2 ]
Li, Chuangen [1 ,2 ]
Zhou, Yunfei [1 ,2 ]
Wang, Guoping [1 ,2 ]
Kang, Wei [5 ]
Ng, Enders Kwok-wai [3 ]
Yu, Jun [1 ,2 ]
机构
[1] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, CUHK Shenzhen Res Inst, Inst Digest Dis, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, CUHK Shenzhen Res Inst, Dept Med & Therapeut,State Key Lab Digest Dis, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, Dept Surg, Hong Kong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Precis Med, Guangzhou, Guangdong, Peoples R China
[5] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Peoples R China
基金
国家重点研发计划;
关键词
COLORECTAL CANCER; BACTERIAL PATHOGENESIS; BILE ACID METABOLISM; BILE-ACIDS; INTESTINAL PERMEABILITY; COLON CARCINOGENESIS; FECAL SAMPLES; ACTIVATION; CELLS; CESSATION; EXPOSURE; RECEPTOR; MURINE;
D O I
10.1136/gutjnl-2021-325021
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objective Cigarette smoking is a major risk factor for colorectal cancer (CRC). We aimed to investigate whether cigarette smoke promotes CRC by altering the gut microbiota and related metabolites. Design Azoxymethane-treated C57BL/6 mice were exposed to cigarette smoke or clean air 2 hours per day for 28 weeks. Shotgun metagenomic sequencing and liquid chromatography mass spectrometry were parallelly performed on mice stools to investigate alterations in microbiota and metabolites. Germ-free mice were transplanted with stools from smoke-exposed and smoke-free control mice. Results Mice exposed to cigarette smoke had significantly increased tumour incidence and cellular proliferation compared with smoke-free control mice. Gut microbial dysbiosis was observed in smoke-exposed mice with significant differential abundance of bacterial species including the enrichment of Eggerthella lenta and depletion of Parabacteroides distasonis and Lactobacillus spp. Metabolomic analysis showed increased bile acid metabolites, especially taurodeoxycholic acid (TDCA) in the colon of smoke-exposed mice. We found that E. lenta had the most positive correlation with TDCA in smoke-exposed mice. Moreover, smoke-exposed mice manifested enhanced oncogenic MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1/2) signalling (a downstream target of TDCA) and impaired gut barrier function. Furthermore, germ-free mice transplanted with stools from smoke-exposed mice (GF-AOMS) had increased colonocyte proliferation. Similarly, GF-AOMS showed increased abundances of gut E. lenta and TDCA, activated MAPK/ERK pathway and impaired gut barrier in colonic epithelium. Conclusion The gut microbiota dysbiosis induced by cigarette smoke plays a protumourigenic role in CRC. The smoke-induced gut microbiota dysbiosis altered gut metabolites and impaired gut barrier function, which could activate oncogenic MAPK/ERK signalling in colonic epithelium.
引用
收藏
页码:2439 / 2450
页数:12
相关论文
共 40 条
[1]   Human gut bacterial metabolism drives Th17 activation and colitis [J].
Alexander, Margaret ;
Ang, Qi Yan ;
Nayak, Renuka R. ;
Bustion, Annamarie E. ;
Sandy, Moriah ;
Zhang, Bing ;
Upadhyay, Vaibhav ;
Pollard, Katherine S. ;
Lynch, Susan, V ;
Turnbaugh, Peter J. .
CELL HOST & MICROBE, 2022, 30 (01) :17-+
[2]   Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut [J].
Allais, Liesbeth ;
Kerckhof, Frederiek-Maarten ;
Verschuere, Stephanie ;
Bracke, Ken R. ;
De Smet, Rebecca ;
Laukens, Debby ;
Van den Abbeele, Pieter ;
De Vos, Martine ;
Boon, Nico ;
Brusselle, Guy G. ;
Cuvelier, Claude A. ;
Van de Wiele, Tom .
ENVIRONMENTAL MICROBIOLOGY, 2016, 18 (05) :1352-1363
[3]   The early increase in intestinal permeability and systemic endotoxin exposure in patients with severe acute pancreatitis is not associated with systemic bacterial translocation: Molecular investigation of microbial DNA in the blood [J].
Ammori, BJ ;
Fitzgerald, P ;
Hawkey, P ;
McMahon, MJ .
PANCREAS, 2003, 26 (01) :18-22
[4]   Smoking Cessation Alters Intestinal Microbiota: Insights from Quantitative Investigations on Human Fecal Samples Using FISH [J].
Biedermann, Luc ;
Bruelisauer, Karin ;
Zeitz, Jonas ;
Frei, Pascal ;
Scharl, Michael ;
Vavricka, Stephan R. ;
Fried, Michael ;
Loessner, Martin J. ;
Rogler, Gerhard ;
Schuppler, Markus .
INFLAMMATORY BOWEL DISEASES, 2014, 20 (09) :1496-1501
[5]   Smoking Cessation Induces Profound Changes in the Composition of the Intestinal Microbiota in Humans [J].
Biedermann, Luc ;
Zeitz, Jonas ;
Mwinyi, Jessica ;
Sutter-Minder, Eveline ;
Rehman, Ateequr ;
Ott, Stephan J. ;
Steurer-Stey, Claudia ;
Frei, Anja ;
Frei, Pascal ;
Scharl, Michael ;
Loessner, Martin J. ;
Vavricka, Stephan R. ;
Fried, Michael ;
Schreiber, Stefan ;
Schuppler, Markus ;
Rogler, Gerhard .
PLOS ONE, 2013, 8 (03)
[6]   Smoking and Colorectal Cancer A Meta-analysis [J].
Botteri, Edoardo ;
Iodice, Simona ;
Bagnardi, Vincenzo ;
Raimondi, Sara ;
Lowenfels, Albert B. ;
Maisonneuve, Patrick .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2008, 300 (23) :2765-2778
[7]   Estimation of Absolute Risk of Colorectal Cancer Based on Healthy Lifestyle, Genetic Risk, and Colonoscopy Status in a Population-Based Study [J].
Carr, Prudence R. ;
Weigl, Korbinian ;
Edelmann, Dominic ;
Jansen, Lina ;
Chang-Claude, Jenny ;
Brenner, Hermann ;
Hoffmeister, Michael .
GASTROENTEROLOGY, 2020, 159 (01) :129-+
[8]   Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin-sensitive mechanism in murine and human hepatocytes [J].
Dent, P ;
Fang, YW ;
Gupta, S ;
Studer, E ;
Mitchell, C ;
Spiegel, S ;
Hylemon, PB .
HEPATOLOGY, 2005, 42 (06) :1291-1299
[9]   Estimates of global mortality attributable to smoking in 2000 [J].
Ezzati, M ;
Lopez, AD .
LANCET, 2003, 362 (9387) :847-852
[10]   Tobacco smoking and cancer: A meta-analysis [J].
Gandini, Sara ;
Botteri, Edoardo ;
Iodice, Simona ;
Boniol, Mathieu ;
Lowenfels, Albert B. ;
Maisonneuve, Patrick ;
Boyle, Peter .
INTERNATIONAL JOURNAL OF CANCER, 2008, 122 (01) :155-164