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.

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.

Chronic ethanol consumption is a risk factor for colorectal cancer, and ethanol-induced reactive oxygen species have been suggested to play important roles in the pathogenesis of ethanol-related colorectal cancer (ER-CRC). In this study, the effects of 10-week chronic administration of ethanol on the colonic levels of oxidative stress and advance glycation end product (AGE) levels, as well as fecal microbiota structures, were examined in a mouse model. Chronic oral administration of ethanol in mice (1.0 mL of 1.5% or 5.0% ethanol (v/v) per day per mouse, up to 10 weeks) resulted in the elevation of colonic levels of oxidative stress markers (such as 8-hydroxy-2’-deoxyguanosine and 4-hydroxynonenal) compared to control mice, and this was consistently accompanied by elevated levels of inflammation-associated cytokines and immune cells (Th17 and macrophages) and a decreased level of regulatory T (Treg) cells to produce colonic lesions. It also resulted in an alteration of mouse fecal microbiota structures, reminiscent of the alterations observed in human inflammatory bowel disease, and this appeared to be consistent with the proposed sustained generation of oxidative stress in the colonic environment during chronic ethanol consumption. Moreover, the first experimental evidence that chronic ethanol administration results in elevated levels of advanced glycation end products (AGEs) and their receptors (RAGE) in the colonic tissues in mice is also shown, implying enhanced RAGE-mediated signaling with chronic ethanol administration. The RAGE-mediated signaling pathway has thus far been implicated as a link between the accumulation of AGEs and the development of many types of chronic colitis and cancers. Thus, enhancement of this pathway likely exacerbates the ethanol-induced inflammatory states of colonic tissues and might at least partly contribute to the pathogenesis of ER-CRC.

A facultatively anaerobic, Gram-stain-positive, rod-shaped bacterium, designated strain KB0549 T , was isolated from sesame oil cake. Cells were motile, round-ended rods, and produced central or terminal spores. The cell wall peptidoglycan contained meso-diaminopimelic acid as the diamino acid. The major fatty acids were anteiso-C 15 : 0 and anteiso-C 17 : 0 . The DNA G+C content of strain KB0549 T was 51.9 mol%. On the basis of 16S rRNA gene sequence phylogeny, strain KB0549 T was affiliated with the genus Paenibacillus in the phylum Firmicutes and was most closely related to Paenibacillus cookii with 97.4 % sequence similarity. Strain KB0549 T was physiologically differentiated from P. cookii by the high content of anteiso-C 17 : 0 , inability to grow at 50 6C, spore position, and negative Voges-Proskauer reaction. Based on these unique physiological and phylogenetic characteristics, it is proposed that the isolate represents a novel species, Paenibacillus relictisesami sp. nov.; the type strain is KB0549 T (5JCM 18068 T 5DSM 25385 T ). Ash et al. (1993) proposed that 11 strains belonging to 'Group 3' within the genus Bacillus should be transferred to the genus Paenibacillus. The descriptions of Paenibacillus amylolyticus, Paenibacillus illinoisensis and Paenibacillus chibensis as species within the genus Paenibacillus were later amended by Shida et al. (1997). At the time of writing, the genus Paenibacillus contains 147 species and four subspecies (http://www.bacterio.net/p/paenibacillus.html).Members of the genus Paenibacillus are aerobic or facultatively anaerobic, rod-shaped, endospore-forming bacteria. Species of this genus have been isolated from various sources, including soil (Yoon et al., 2007), rhizosphere (Daane et al., 2002;Kuisiene et al., 2008), compost (Iida et al., 2005Ueda et al., 2013), warm springs (Saha et al., 2005) and human faeces (Hoyles et al., 2012). Several of the characterized strains have useful enzymic activities; for example, Paenibacillus sp. JDR-2 produces xylanase and is, therefore, able to utilize hemicellulosic polysaccharides (St John et al., 2006). Members of the genus Paenibacillus contain meso-diaminopimelic acid as the major diamino acid in peptidoglycan, and have anteiso-C 15 : 0 as the major cellular fatty acid. The DNA G+C content of species ranges from 36 to 59 mol% (Ash et al., 1993;Shida et al., 1997;De Vos et al., 2009). In this communication, we describe the polyphasic taxonomic characterization of a sesaminol-producing bacterium, strain KB0549 T , which was isolated from sesame oil cake (SOC) and was determined to be affiliated with the genus Paenibacillus.Sesaminol is one of several lignans found in sesame oil, having strong antioxidant activity as well as a variety of health benefits to humans (Fukuda et al., 1986;Kang et al., 1998;Kumazawa et al., 2003). Sesame seeds contain large amounts of sesaminol in glycosidic form. Sesaminolis the most abundant lignan in sesame seeds and is therefore a potentially important source of sesaminol. However, due to its bra...

Ethanol is oxidized by alcohol dehydrogenase to acetaldehyde, a recognized carcinogen for the esophagus. However, no previous study has measured the acetaldehyde levels in the esophageal tissue. L-cysteine has been shown to reduce the acetaldehyde levels in the saliva; however, it is unknown whether L-cysteine intake affects the acetaldehyde concentration in the esophageal tissue. The aim of this study was to measure the acetaldehyde concentration in the esophageal tissue after ethanol drinking and evaluate the effect of L-cysteine intake on the acetaldehyde levels in the esophagus. We enrolled 10 male subjects with active acetaldehyde dehydrogenase-2*1/*1 (ALDH2*1/*1) genotype and 10 male subjects with the inactive acetaldehyde dehydrogenase-2*1/*2 (ALDH2*1/*2) genotype, the mean ages of whom were 25.6 and 27.9 years, respectively. In this prospective, single-blind, placebo-controlled study using L-cysteine and placebo lozenges (first and second examination), saliva and blood were collected before and after ethanol drinking. Esophageal tissue was obtained by endoscopic biopsy at 60 minutes after drinking, and the acetaldehyde and ethanol concentrations were measured. The acetaldehyde concentration of the saliva was significantly lower in those taking L-cysteine than in those taking the placebo. Acetaldehyde in the esophageal tissue was detected only in those taking L-cysteine lozenges. There were no correlations between the acetaldehyde concentrations in the esophageal tissue and saliva or blood. In conclusion, we detected acetaldehyde in the human esophageal tissue after ethanol drinking. Unexpectedly, intake of L-cysteine lozenges appears to contribute to detection of acetaldehyde in the esophageal tissue.