Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer.
Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic. However, the effects of chronic ethanol consumption on the human gut microbiome are poorly understood, and the role of gut microbes in the proposed AcH-mediated pathogenesis of ER-CRC remains to be elaborated. Here we analyse and compare the gut microbiota structures of non-alcoholics and alcoholics. The gut microbiotas of alcoholics were diminished in dominant obligate anaerobes (e.g., Bacteroides and Ruminococcus) and enriched in Streptococcus and other minor species. This alteration might be exacerbated by habitual smoking. These observations could at least partly be explained by the susceptibility of obligate anaerobes to reactive oxygen species, which are increased by chronic exposure of the gut mucosa to ethanol. The AcH productivity from ethanol was much lower in the faeces of alcoholic patients than in faeces of non-alcoholic subjects. The faecal phenotype of the alcoholics could be rationalised based on their gut microbiota structures and the ability of gut bacteria to accumulate AcH from ethanol.
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Atsuki
A
Tsuruya
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Akika
A
Kuwahara
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Yuta
Y
Saito
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Haruhiko
H
Yamaguchi
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Takahisa
T
Tsubo
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Shogo
S
Suga
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Makoto
M
Inai
Department of Applied Information Sciences, Graduate School of Information Sciences, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Yuichi
Y
Aoki
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Seiji
S
Takahashi
Suntory World Research Center, Suntory Holdings Ltd., Soraku-gun, Kyoto 619-0284, Japan.
Eri
E
Tsutsumi
Suntory World Research Center, Suntory Holdings Ltd., Soraku-gun, Kyoto 619-0284, Japan.
Yoshihide
Y
Suwa
Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
Hidetoshi
H
Morita
School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo 663-8179, Japan.
Kenji
K
Kinoshita
Division of Cancer Development System, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Yukari
Y
Totsuka
Center for Omics and Bioinformatics, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
Wataru
W
Suda
Center for Omics and Bioinformatics, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
Kenshiro
K
Oshima
Center for Omics and Bioinformatics, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
Masahira
M
Hattori
National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa 239-0841, Japan.
Takeshi
T
Mizukami
National Hospital Organization Kurihama Medical and Addiction Center, Yokosuka, Kanagawa 239-0841, Japan.
Akira
A
Yokoyama
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Takefumi
T
Shimoyama
Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Miyagi 980-8579 Japan.
Toru
T
Nakayama
D000079:Acetaldehyde / Q000737:chemistry / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000437:Alcoholism / Q000382:microbiology* / Q000473:pathology; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics; D001439:Bacteroides / Q000235:genetics / Q000302:isolation & purification*; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D000431:Ethanol / Q000378:metabolism*; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D025341:Principal Component Analysis; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics; D045857:Ruminococcus / Q000235:genetics / Q000302:isolation & purification*; D017422:Sequence Analysis, DNA; D013291:Streptococcus / Q000235:genetics / Q000302:isolation & purification*; D055815:Young Adult
D012336:RNA, Ribosomal, 16S; D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde