Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source

Abstract

Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and protein adduction, oxidative stress, endoplasmic reticulum stress, immune dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of endogenous and exogenous acrolein sources, acrolein’s mode of action, and its metabolic fate. Recent reports underpin the finding that gut microbial glycerol metabolism leading to the formation of reuterin is an additional source of endogenous acrolein. Reuterin is an antimicrobial multicomponent system consisting of 3-hydroxypropionaldehyde, its dimer and hydrate, and also acrolein. The major conclusion is that gut microbes can metabolize glycerol to reuterin and that this transformation occurs in vivo. Given the known toxicity of acrolein, the observation that acrolein is formed in the gut necessitates further investigations on functional relevance for gut microbiota and the host.

Gut microbial beta-glucuronidase and glycerol/diol dehydratase activity contribute to dietary heterocyclic amine biotransformation

“…While HCA-M1 cytotoxicity to colon epithelium cannot be excluded, the high concentrations required to reduce cell viability are not consistent with this being a process of significant concern specifically in the context of addressing HCA mutagenicity and carcinogenesis [20, 21, 41]. Nonetheless, the HCA to HCA-M1 conversion process does involve the intermediate formation of acrolein [18, 20], and we recently proposed bacterial glycerol metabolism as a new endogenous source of acrolein [42]. Acrolein is an unspecific antimicrobial agent, which may influence gut microbial composition as some bacteria are more sensitive to acrolein than other taxa [18].…”

“…Acrolein is an unspecific antimicrobial agent, which may influence gut microbial composition as some bacteria are more sensitive to acrolein than other taxa [18]. In addition, acrolein can cause oxidative stress and disrupt cell homeostasis in colon epithelial cells [42]. The rate of PhIP-M1 formation is proportional to acrolein concentration [18], suggesting a requirement for relatively high acrolein levels.…”

Decontamination of Minimally-Processed Fresh Lettuce Using Reuterin Produced by Lactobacillus reuteri

“…The main antimicrobial component of the reuterin system, acrolein, is highly volatile, colorless, and may be present in many food, sometimes at high levels of more than 4.0 ng/g such as in potato chips fried in corn oil ( Watzek et al, 2012 ). Acrolein is considered a highly cytotoxic compound after a single exposure, hence a tolerable daily intake of 0.75 mg/kg body weight/day was suggested ( Abraham et al, 2011 ; Fernández-Cruz et al, 2016 ; Zhang et al, 2018 ). In our study, between 0.6–1.6 mM and 0.1–0.7 mM of acrolein was lost during washing with ER and CR, respectively.…”

“…Aside volatilization and reaction with microbes and plant components, reversible, first-order hydration of acrolein to 3-HPA which is enhanced at low temperatures may be a significant pathway for the elimination ( Engels et al, 2016 ). However, little is known about reactions and degradation products of acrolein which is a very reactive component ( Engels et al, 2016 ; Zhang et al, 2017 , 2018 ). Taken together, the absence of detectable acrolein in the treated lettuce suggest safety of reuterin washing at effective acrolein concentrations, but additional testing may be needed to identify potential by-products of acrolein.…”

The Human Fecal Microbiota Metabolizes Foodborne Heterocyclic Aromatic Amines by Reuterin Conjugation and Further Transformations

“…Dietary glycerol, either free or liberated from glycerides, enters the human gut, where reuterin‐producing bacteria (glycerol/diol dehydratase) convert it into 3‐hydroxypropionaldehyde ( 3 ), which spontaneously dehydrates to acrolein ( 6 ) . Because of its high reactivity, 6 can form covalent adducts with HAAs, in particular α‐carbolines and 2‐aminoimidazoazarenes, in a Michael type addition.…”