Acrolein contributes strongly to antimicrobial and heterocyclic amine transformation activities of reuterin

Abstract

Glycerol/diol dehydratases catalyze the conversion of glycerol to 3-hydroxypropionaldehyde (3-HPA), the basis of a multi-component system called reuterin. Reuterin has antimicrobial properties and undergoes chemical conjugation with dietary heterocyclic amines (HCAs). In aqueous solution reuterin is in dynamic equilibrium with the toxicant acrolein. It was the aim of this study to investigate the extent of acrolein formation at various physiological conditions and to determine its role in biological and chemical activities. The application of a combined novel analytical approach including IC-PAD, LC-MS and NMR together with specific acrolein scavengers suggested for the first time that acrolein, and not 3-HPA, is the active compound responsible for HCA conjugation and antimicrobial activity attributed to reuterin. As formation of the HCA conjugate was observed in vivo, our results imply that acrolein is formed in the human gut with implications on detoxification of HCAs. We propose to re-define the term reuterin to include acrolein.

Enhanced Probiotic Potential of Lactobacillus reuteri When Delivered as a Biofilm on Dextranomer Microspheres That Contain Beneficial Cargo

“…With regard to L. reuteri- induced release of substance potentially beneficial to the host, reuterin has been suggested to inhibit competition by other gut flora, and histamine has been shown to have anti-inflammatory effects. Although the secondary metabolites produced from glycerol metabolism to generate reuterin (e.g., acrolein) and histamine could result in adverse effects at high levels, the maximum quantities generated with our formulations are <1% and <40% less than what is thought to be problematic in humans for acrolein (Figure S7) and histamine, respectively (Maintz and Novak, 2007; Thomas et al, 2012; Engels et al, 2016). Ongoing and future experiments utilizing L. reuteri adhered to DMs will test the putative aforementioned beneficial cargos in an in vivo animal model (Olson et al, in preparation) to demonstrate both safety and efficacy.…”

“…L. reuteri is a popular choice for commercialization due to its production of lactic acid and the antimicrobial compound reuterin, a metabolite of glycerol metabolism known chemically as 3-hydroxypropionaldehyde (3-HPA), which typically exists in equilibrium with other downstream products such as 3-HPA hydrate and acrolein (Talarico et al, 1988; Engels et al, 2016). Reuterin induces oxidative stress in a broad range of microorganisms (Schaefer et al, 2010), and is highly effective at inhibiting growth of many gastrointestinal pathogens (el-Ziney and Debevere, 1998; Arques et al, 2004; Spinler et al, 2008; De Weirdt et al, 2012).…”

Effect of cryopreservation and lyophilization on viability and growth of strict anaerobic human gut microbes

“…These data may be explained by the ability of E. hallii to convert glycerol to reuterin (Engels et al, 2016a). Reuterin is a broad-spectrum antimicrobial system, which, at physiological conditions, mainly consists of 3-hydroxypropionaldehyde (3-HPA), its hydrate and dimer, and acrolein (Engels et al, 2016b). Reuterin can inhibit growth of the producer strain.…”

Isolation and comparative genomic analysis of reuterin-producingLactobacillus reuterifrom poultry gastrointestinal tract

“…Glycerol, a second substrate of PduCDE, is transformed to the intermediate 3-hydroxypropionaldehyde which can be further metabolized to 1,3-propanediol or 3-hydroxypropionate [7]. 3-HPA produced from glycerol is released from the cell forming the dynamic multicompound reuterin system, with broad antimicrobial spectrum and consisting of 3-HPA, its hydrate and dimer and acrolein [8,9]. Acrolein, a highly reactive toxicant, was recently shown to be the main component for the antimicrobial activity of reuterin [10,11].…”

“…8.0) were collected by centrifugation, resuspended in 600 mM glycerol solution and incubated at 25 o C for 2h. For reuterin biosynthesis, the concentrations of glycerol, 3-HPA and acrolein were measured by high performance liquid chromatography using refractive index (HLPC-RI, Hitachi LaChrome, Merck, Dietikon, Switzerland) and ion-exclusion chromatography with pulsed-amperometric detection (IC-PAD) analysis, respectively[8,11]. For HPLC-RI, an Aminex HPx-87H column and sulfuric acid (10 mM) was used The concentration range tested was 0.016 to 256 μg/mg, except for CIP (0.002 to 32 μg/mL).…”