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.

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

Aims: The importance of ethanol oxidation by intestinal aerobes and facultative anaerobes under aerobic conditions in the pathogenesis of ethanol-related colorectal cancer has been proposed. However, the role of obligate anaerobes therein remains to be established, and it is still unclear which bacterial species, if any, are most important in the production and/or elimination of carcinogenic acetaldehyde under such conditions. This study was undertaken to address these issues.

Catalytic removal of acetaldehyde in saliva by a Gluconobacter strain.

Acetaldehyde (AA) accumulates in the oral cavity after alcohol intake and is responsible for an increased risk of alcohol-related upper aerodigestive tract (UDAT) cancer among aldehyde dehydrogenase 2-inactive heterozygotes in particular. Thus, the removal of AA from the saliva to a level below its mutagenic concentration (50 μM) after drinking is a potentially straightforward method for reducing the risk of alcohol-related UDAT cancer. Although microbial cells with AA-decomposing activity could potentially serve as a useful agent for the catalytic removal of AA from the saliva without the supplemental addition of cofactors, these cells generally exhibit strong AA-producing activity from ethanol, which is present in excess (50mM) over AA (100 μM) in the saliva after drinking.

Analysis of N(ε) -ethyllysine in human plasma proteins by gas chromatography-negative ion chemical ionization/mass spectrometry as a biomarker for exposure to acetaldehyde and alcohol.

Background: N(ε) -ethyllysine (NEL) is a major stable adduct formed by the reaction of acetaldehyde (AA) with lysine residues in proteins. However, its occurrence and levels in biological specimens and its relationship with AA/alcohol exposure-associated disorders have not been fully elucidated. In this study, we have developed a sensitive and specific method to quantitate NEL levels in human plasma proteins.

Enantioselective total synthesis of aperidine.

An efficient total synthesis of aperidine was accomplished using a Rh-catalyzed C-H insertion of a cis-dihydrobenzofuran ring. To circumvent the facile epimerization of the cis-dihydrobenzofuran ring, we designed and prepared the C-H insertion precursor diazoamide by Raines' protocol. Finally, the efficient incorporation of a guanidine group and mild deprotection conditions yielded this labile natural product.

Inhibitory effects of whisky congeners on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.

Whisky is matured in oak casks. Many nonvolatile substances (whisky congeners, WC) seep from the oak cask during the maturing process. In this study, three antiallergic agents (syringaldehyde, SA; lyoniresinol, Lyo; and ellagic acid, EA) were isolated from WC.

Polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 and the blood and salivary ethanol and acetaldehyde concentrations of Japanese alcoholic men.

Background: The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers.

Methods: We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before.

Results: The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria.

Structure-activity relationship study on alpha1 adrenergic receptor antagonists from beer.

Hordatine A and aperidine have been previously isolated from beer as active ingredients, which bind to muscarinic M3 receptor. In addition, these compounds have exhibited antagonist activity against the alpha1A adrenoceptor. Although the relative structures of these two molecules have previously been determined, the absolute stereochemistry was unclear.

Stimulatory effect of N-methyltyramine, a congener of beer, on pancreatic secretion in conscious rats.

Background: Alcoholic beverages stimulate gastric acid secretion and increase the appetite. Although ingested ethanol stimulates pancreatic secretion, alcoholic beverages contain several congeners. N-methyltyramine (NMT) was isolated from beer as a factor in stimulating gastric acid secretion.

Subchronic (13-week) oral toxicity study of dihomo-gamma-linolenic acid (DGLA) oil in rats.

Dihomo-gamma-linolenic acid (DGLA) is one of the essential fatty acids, and has anti-inflammatory and anti-allergic effects. To assess the toxicity of a novel DGLA oil produced by the fungus Mortierella alpina, we examined it in the Ames test and in acute and subchronic oral toxicity tests in rats. In the Ames test, no mutagenicity was found up to 5000 microg/plate.

Isolation and structure of whiskey polyphenols produced by oxidation of oak wood ellagitannins.

Three new phenolic compounds named whiskey tannins A and B and carboxyl ellagic acid were isolated from commercial Japanese whiskey, along with gallic acid, ellagic acid, brevifolin carboxylic acid, three galloyl glucoses, a galloyl ester of phenolic glucoside, 2,3-(S)-hexahydroxydiphenoylglucose, and castacrenin B. Whiskey tannins A and B were oxidation products of a major oak wood ellagitannin, castalagin, in which the pyrogallol ring at the glucose C-1 position of castalagin was oxidized to a cyclopentenone moiety. These tannins originated from ellagitannins contained in the oak wood used for barrel production; however, the original oak wood ellagitannins were not detected in the whiskey.

Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde dehydrogenase-2 genotype.

Background: Acetaldehyde is suspected of playing a critical role in cancer development in the upper aerodigestive tract (UADT). The high salivary acetaldehyde levels after alcohol drinking are partly due to acetaldehyde production by oral bacteria. Some alcoholic beverages, especially Calvados and shochu, contain very high levels of acetaldehyde.

Contribution of the alcohol dehydrogenase-1B genotype and oral microorganisms to high salivary acetaldehyde concentrations in Japanese alcoholic men.

The less-active homozygous alcohol dehydrogenase-1B (ADH1B*1/*1) and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/*2) increase the risk of upper aerodigestive tract cancer (UADTC) in Japanese alcoholics. We evaluated associations between ADH1B/ALDH2 genotypes and the blood and salivary ethanol/acetaldehyde levels of 80 Japanese alcoholic men in the morning when they first visited our hospital after drinking the day before. Higher levels of ethanol persisted in the blood for longer periods in ADH1B*1/*1 carriers (n = 25) than in ADH1B*2 allele carriers after adjustment for the amount and time of the preceding alcohol consumption and body weight [median (25th-75th %): 20.

Structural determination of two active compounds that bind to the muscarinic M3 receptor in beer.

Background: It is known that beer accelerates gastrointestinal motility in humans. Our previous studies showed that beer congener stimulates gastrointestinal motility by directly stimulating the muscarinic M3 receptor. Further, we isolated 2 active compounds (compounds A and B) from beer by liquid chromatography.

Effect of xylooligosaccharide intake on severe constipation in pregnant women.

Xylooligosaccharides (XOS) are mainly composed of two or three xylose units with beta-1,4 linkages. They are obtained by hemicellulose hydrolysis, which is relatively abundant in the cell walls of grains. XOS increases the number of intestinal Bifidobacterium in humans, and maintains the fecal water content within the normal range.

Isolation of stimulants of gastrointestinal motility in beer.

Background: Among various alcoholic beverages, it has reported that beer has a potent activity to stimulate gastric emptying. Our previous studies showed that beer congener stimulated gastrointestinal motility by directly stimulating muscarinic M3 receptor, present in smooth muscles of the gastrointestinal tract. However, active components that account for the action have yet to be identified.

Effects of fusel oil on animal hangover models.

Background: Fusel oil has been reported to have undesirable side effects such as hangover. However, the relationship between fusel oil and hangover has been investigated insufficiently. In this study, we investigated the effects of fusel oil and their ingredients contained in alcoholic beverages by using animal hangover models.

Influence of moderate drinking on purine and carbohydrate metabolism.

Background: We examined the influences of a moderate intake level of three types of alcoholic beverages--beer, whisky, and Shochu (Japanese distilled liquor)--on purine and carbohydrate metabolism and excretion in healthy male volunteers, concerning (1) the extent of contribution of purine bodies contained in beer to uric acid metabolism and (2) a comparison between two types of distilled spirits with (whisky) and without (Shochu) aging in oak wood barrel storage.

Methods: Three sets of studies were conducted in which 10 to 13 healthy adult men were instructed to drink three types of alcoholic beverages at a slightly higher level (0.8 ml of ethanol equivalent/kg body weight) than moderate drinking (approximately 30.

Beer congener stimulates gastrointestinal motility via the muscarinic acetylcholine receptors.

Background: Ethanol and alcoholic beverages are known to affect upper gastrointestinal motility in humans. Beer has been reported to accelerate gastric emptying compared with other beverages that contain the same ethanol concentrations. In this study, we investigated the mechanism that underlies the effects of beer congener on gastrointestinal motility.