Major Anaerobic Bacteria Responsible for the Production of Carcinogenic Acetaldehyde from Ethanol in the Colon and Rectum

Tsuruya, Atsuki; Kuwahara, Akika; Saito, Yuta; Yamaguchi, Haruhiko; Tenma, Natsuki; Inai, Makoto; Takahashi, Shigetoshi; Tsutsumi, Eri; Suwa, Yoshihide; Totsuka, Yukari; Suda, Wataru; Oshima, Koichiro; Hattori, Masahira; Mizukami, Takeshi; Yokoyama, Akira; Shimoyama, Takefumi; Nakayama, Tôru

doi:10.1093/alcalc/agv135

Cited by 51 publications

(59 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There was a statistically significant correlation between microbial ADH activity and acetaldehyde production from ethanol in the colon [58]. More than 500 bacterial strains isolated from the feces of Japanese alcoholics were phylogenetically characterized, and their ability to produce acetaldehyde from ethanol beyond the minimum mutagenic concentration was examined [59]. Among these, some obligate anaerobes were found to be potential acetaldehyde accumulators [59].…”

Section: Mechanisms Underlying Alcohol-induced Gastric and Colonicmentioning

confidence: 99%

“…More than 500 bacterial strains isolated from the feces of Japanese alcoholics were phylogenetically characterized, and their ability to produce acetaldehyde from ethanol beyond the minimum mutagenic concentration was examined [59]. Among these, some obligate anaerobes were found to be potential acetaldehyde accumulators [59]. Ethanol oxidation by intestinal obligate anaerobes under aerobic conditions in the colon and rectum is hence likely to play an important role in the pathogenesis of alcohol-associated colorectal cancer [59].…”

Section: Mechanisms Underlying Alcohol-induced Gastric and Colonicmentioning

confidence: 99%

“…Among these, some obligate anaerobes were found to be potential acetaldehyde accumulators [59]. Ethanol oxidation by intestinal obligate anaerobes under aerobic conditions in the colon and rectum is hence likely to play an important role in the pathogenesis of alcohol-associated colorectal cancer [59]. Alcohol administration gave rise to very high intracolonic acetaldehyde levels in rat, which were markedly decreased by concomitant treatment with ciprofloxacin, an antibiotics [60].…”

Section: Mechanisms Underlying Alcohol-induced Gastric and Colonicmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Basis of Alcohol-Related Gastric and Colon Cancer

Lee

2017

IJMS

122

View full text Add to dashboard Cite

Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2. Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of β-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. Alcohol also generates reactive oxygen species (ROS) by suppressing the expression of antioxidant and cytoprotective enzymes and inducing expression of CYP2E1 which contribute to the metabolic activation of chemical carcinogens. Besides exerting genotoxic effects by directly damaging DNA, ROS can activates signaling molecules involved in inflammation, metastasis and angiogenesis. In addition, alcohol consumption induces folate deficiency, which may result in aberrant DNA methylation profiles, thereby influencing cancer-related gene expression.

show abstract

Section: Mechanisms Underlying Alcohol-induced Gastric and Colonicmentioning

confidence: 99%

Section: Mechanisms Underlying Alcohol-induced Gastric and Colonicmentioning

confidence: 99%

Section: Mechanisms Underlying Alcohol-induced Gastric and Colonicmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Basis of Alcohol-Related Gastric and Colon Cancer

Lee

2017

IJMS

122

View full text Add to dashboard Cite

show abstract

“…The microbiome is also involved in the metabolism of alcohol; microbial co-oxidation of ethanol increases the production of acetaldehyde. Microbial geni involved in ethanol oxidation have been identified as gram-positive Ruminococcus , Collinsella , Coriobacterium, Bifidobacterium and gram-negative Prevotella (103). Escherichia coli has also been linked to the accumulation of acetaldehyde in the intestinal lumen (104).…”

Section: Microbial Co-exposure and Mechanisms Of Colorectal Cancermentioning

confidence: 99%

Environmental Influences in the Etiology of Colorectal Cancer: the Premise of Metabolomics

et al. 2017

View full text Add to dashboard Cite

Purpose of Review In this review we discuss how environmental exposures predominate the etiology of colorectal cancer (CRC). With CRC being a personalized disease influenced by genes and environment, our goal was to explore the role metabolomics can play in identifying exposures, assessing the interplay between co-exposures, and the development of personalized therapeutic interventions. Recent Findings Approximately 10 % of CRC cases can be explained by germ-line mutations, whereas the prevailing majority are caused by an initiating exposure event occurring decades prior to diagnosis. Recent research has shown that dietary metabolites are linked to a procarcinogenic or protective environment in the colon which is modulated by the microbiome. In addition, excessive alcohol has been shown to increase the risk of CRC and is dependent on diet (folate), the response of microbiome, and genetic polymorphisms within the folate and alcohol metabolic pathways. Metabolomics can not only be used to identify this modulation of host metabolism, which could affect the progression of the tumors but also response to targeted therapeutics. Summary This review highlights the current understanding of the multifaceted etiology and mechanisms of CRC development but also highlights where the field of metabolomics can contribute to a greater understanding of environmental exposure in CRC.

show abstract

“…Of note, gut microbial makeup of these dysbiotic conditions includes both alcohol-producing [26,51,62,64,[70][71][72][73][74][75][76][77][78][79] and alcoholdegrading microorganisms [62,[80][81][82][83][84][85]. In this setting, both host and microbial enzymes of the oro-gastrointestinal tract produce ethanol and oxidize it into acetaldehyde in a dose-dependent manner [70,83,[86][87][88][89][90][91].…”

Section: Oro-gastrointestinal Production Of Ethanol and Acetaldehydementioning

confidence: 99%

Nonalcoholic fatty pancreas disease as an endogenous alcoholic fatty pancreas disease

Medeiros¹,

Lima²

2016

Gastroenterol Hepatol Endosc

View full text Add to dashboard Cite

Nonalcoholic fatty pancreas disease (NAFPD) is closely linked to nonalcoholic steatohepatitis (NASH), suggesting that the two conditions share a common etiopathogenetic background. In Addition, growing evidence indicates that endogenous ethanol (EE) plays a fundamental role in NASH pathogenesis. Accordingly, it is intuitively appealing to assume that EE plays also a causative role in NAFPD development. This connection is further supported by the finding that NAFPD shares with alcoholic fatty pancreas disease (AFPD) similar metabolic signaling pathways and histopathological features. However, low blood alcohol concentrations (BAC) along with the alleged inability of gut microbiota to produce toxic amounts of ethanol are the main obstacles to validate the idea of an endogenous alcoholic fatty pancreas disease (EAFPD). Here, we provide a mechanistic explanation reconciling the EAFPD hypothesis with these apparently conflicting observations. The key conclusions of our investigation are as follows. First, ethanol is a prodrug, implicating that under extensive presystemic metabolism BACs can be low and/ or absent. Second, oro-gastrointestinal microbiota may produce higher amounts of ethanol than those required to cause AFPD. Last, livers of NASH/NAFPD individuals overexpress all genes encoding alcohol-metabolizing enzymes identically to livers of patients with alcoholic hepatitis. Even more importantly, the upregulation of these genes is higher in the early steatotic stage of nonalcoholic fatty liver disease than in alcoholic hepatitis. This suggests a greater exposure of the liver, and by extension, of the pancreas, to ethanol in the former than in the latter condition. In summary, this paper provides a mechanistic framework for how NAFPD indeed may be an EAFPD.

show abstract

Major Anaerobic Bacteria Responsible for the Production of Carcinogenic Acetaldehyde from Ethanol in the Colon and Rectum

Abstract: Ethanol oxidation by intestinal obligate anaerobes under aerobic conditions in the colon and rectum could also play an important role in the pathogenesis of ethanol-related colorectal cancer.

Cited by 51 publications

References 31 publications

Molecular Basis of Alcohol-Related Gastric and Colon Cancer

Molecular Basis of Alcohol-Related Gastric and Colon Cancer

Environmental Influences in the Etiology of Colorectal Cancer: the Premise of Metabolomics

Nonalcoholic fatty pancreas disease as an endogenous alcoholic fatty pancreas disease

Contact Info

Product

Resources

About