The Impact of Alcohol Consumption and Oral Microbiota on Upper Aerodigestive Tract Carcinomas: A Pilot Study

Abstract

Alcohol consumption is associated with oxidative stress and an increased risk of carcinoma of the upper aero-digestive tract (UADT). Recently, it has been found that some microorganisms in the human oral cavity may locally metabolize ethanol, forming acetaldehyde, a carcinogenic metabolite of alcohol. In a cohort of patients first visited for UADT cancers, we estimated their alcohol consumption by measuring Ethyl Glucuronide/EtG (a long-lasting metabolite of ethanol) in the hair and carbohydrate-deficient transferrin/CDT (short-term index of alcohol intake) in the serum. Moreover, we analyzed, by culture-based methods, the presence of Neisseria subflava, Streptococcus mitis, Candida albicans, and glabrata (microorganisms generating acetaldehyde) in the oral cavity. According to the EtG values, we correlated drinking alcohol with endogenous oxidative stress and the investigated microorganism’s presence. We found that 55% of heavy drinkers presented microorganisms generating acetaldehyde locally. Moreover, we found that the presence of oral acetaldehyde-producing bacteria correlates with increased oxidative stress compared to patients without such bacteria. As for the study of alcohol dehydrogenase gene polymorphisms (the enzyme that transforms alcohol to acetaldehyde), we found that only the “CGTCGTCCC” haplotype was more frequent in the general population than in carcinoma patients. This pilot study suggests the importance of estimating alcohol consumption (EtG), the presence of bacteria producing acetaldehyde, and oxidative stress as risk factors for the onset of oral carcinomas.

The coming future: The role of the oral–microbiota–brain axis in aroma release and perception

“…Acetaldehyde, an aroma compound primarily derived from ethanol, has been associated with the oral microbiota's role in aromatic compound production and metabolism. Research has shown that bacteria Neisseria subflava, Streptococcus mitis, Candida albicans , and C. glabrata in the human oral cavity exhibit high alcohol dehydrogenase activity, converting ethanol to acetaldehyde (Fiore et al., 2023). Human aldehyde dehydrogenases have recently been discovered to metabolize odorant aldehydes.…”

Intratumor microbiome: selective colonization in the tumor microenvironment and a vital regulator of tumor biology

“…Similarly, E. coli carrying the pks‐island‐produced colibactin also induced a novel mutational signature in oral squamous cell carcinoma and in other mucosal tumor types 69 . Furthermore, in oral and even upper aerodigestive tract carcinomas, the residing of certain bacteria, including Neisseria subflava , Streptococcus mitis , Candida albicans , Glabrata , etc., that are generally non‐pathogenic, could convert alcohol into carcinogen acetaldehyde and thus play a subtle role in alcohol‐related carcinogenesis in human oral cancer 70,71 . Acetaldehyde causes DNA damage and blocks DNA repair, and is usually further metabolized by aldehyde dehydrogenase (ALDH) in the liver, while in the oral cavity, the activity of ALDH is relatively low, resulting in the long existence of acetaldehyde and more deteriorating results 72,73 .…”