Factors influencing the fate of chemical food safety hazards in the terrestrial circular primary food production system-A comprehensive review.

Food safety is recognized as a major hurdle in the transition toward circular food production systems due to the potential reintroduction and accumulation of chemical contaminants in these food systems. Effectively managing these hazardous contaminants in a risk-based manner requires quantitative insights into the factors influencing the presence and fate of contaminants in the entire circular food chain. A systematic literature review was performed to gain an up-to-date overview of the known factors and their influence on the transfer and accumulation of contaminants. This review focused on the terrestrial circular primary food production system, including the pathways between waste- or byproduct-based fertilizers, soil, crops, animal feed, and farmed animals. This review revealed an imbalance in research regarding the different pathways: studies on the soil-to-crop pathway were most abundant. The factors identified can be categorized as compound-related (intrinsic) factors, such as hydrophobicity, molecular weight, and chain length, and extrinsic factors, such as soil organic matter and carbon, pH, milk yield of cows, crop age, and biomass. Quantitative data on the influence of the identified factors were limited. Most studies quantified the influence of individual factors, whereas only a few studies quantified the combined effect of multiple factors. By providing a holistic insight into the influential factors and the quantification of their influence on the fate of contaminants, this review contributes to the improvement of food safety management for chemical hazards when transitioning to a circular food system.

Differences in gut microbial fructoselysine degradation activity between breast-fed and formula-fed infants.

The Amadori product fructoselysine is formed upon heating of food products and is abundantly present in infant formula while being almost absent in breast milk. The human gut microbiota can degrade fructoselysine for which interindividual differences have been described for adults. The aim of this study is to compare functional differences in microbial fructoselysine degradation between breast-fed and formula-fed infants, in view of their different diets and resulting different fructoselysine exposures. First, a publicly available metagenomic dataset with metagenome-assembled genomes (MAGs) from infant fecal samples was analyzed and showed that query genes involved in fructoselysine degradation (frlD/yhfQ) were abundantly present in multiple bacterial taxa in the fecal samples, with a higher prevalence in the formula-fed infants. Next, fecal samples collected from exclusively breast-fed and formula-fed infants were anaerobically incubated with fructoselysine. Both groups degraded fructoselysine, however the fructoselysine degradation activity was significantly higher by fecal samples from formula-fed infants. Overall, this study provides evidence that infant formula feeding, leading to increased dietary fructoselysine exposure, seems to result in an increased fructoselysine degradation activity in the gut microbiota of infants. This indicates that the infant gut microbiota adapts towards dietary fructoselysine exposure.

Inter- and Intraindividual Differences in the Capacity of the Human Intestinal Microbiome in Fecal Slurries to Metabolize Fructoselysine and Carboxymethyllysine.

The advanced glycation endproduct carboxymethyllysine and its precursor fructoselysine are present in heated, processed food products and are considered potentially hazardous for human health. Upon dietary exposure, they can be degraded by human colonic gut microbiota, reducing internal exposure. Pronounced interindividual and intraindividual differences in these metabolic degradations were found in anaerobic incubations with human fecal slurries in vitro. The average capacity to degrade fructoselysine was 27.7-fold higher than that for carboxymethyllysine, and degradation capacities for these two compounds were not correlated (R2 = 0.08). Analysis of the bacterial composition revealed that interindividual differences outweighed intraindividual differences, and multiple genera were correlated with the individuals' carboxymethyllysine and fructoselysine degradation capacities (e.g., Akkermansia, Alistipes).

Differences in kinetics and dynamics of endogenous versus exogenous advanced glycation end products (AGEs) and their precursors.

Advanced glycation end products (AGEs) and their precursors, referred to as glycation products, are a heterogenous group of compounds being associated with adverse health effects. They are formed endogenously and in exogenous sources including food. This review investigates the roles of endogenously versus exogenously formed glycation products in the potential induction of adverse health effects, focusing on differences in toxicokinetics and toxicodynamics, which appeared to differ depending on the molecular mass of the glycation product. Based on the available data, exogenous low molecular mass (LMM) glycation products seem to be bioavailable and to contribute to dicarbonyl stress and protein cross-linking resulting in formation of endogenous AGEs. Bioavailability of exogenous high molecular mass (HMM) glycation products appears limited, while these bind to the AGE receptor (RAGE), initiating adverse health effects. Together, this suggests that RAGE-binding in relevant tissues will more likely result from endogenously formed glycation products. Effects on gut microbiota induced by glycation products is proposed as a third mode of action. Overall, studies which better discriminate between LMM and HMM glycation products and between endogenous and exogenous formation are needed to further elucidate the contributions of these different types and sources of glycation products to the ultimate biological effects.

The Influence of Intracellular Glutathione Levels on the Induction of Nrf2-Mediated Gene Expression by α-Dicarbonyl Precursors of Advanced Glycation End Products.

α-Dicarbonyl compounds, particularly methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), are highly reactive precursors for the formation of advanced glycation end products (AGEs). They are formed in vivo and during food processing. This study aimed to investigate the role of intracellular glutathione (GSH) levels in the induction of Nrf2-mediated gene expression by α-dicarbonyl compounds. The reactions between α-dicarbonyl compounds (MGO, GO, and 3-DG) and GSH were studied by LC-MS in a cell-free system. It was shown that these three α-dicarbonyl compounds react instantaneously with GSH, with the GSH-mediated scavenging decreasing in the order MGO > GO > 3DG. Furthermore, in a cell-based reporter gene assay MGO, GO, and 3-DG were able to induce Nrf2-mediated gene expression in a dose-dependent manner. Modulation of intracellular GSH levels showed that the cytotoxicity and induction of the Nrf2-mediated pathway by MGO, GO and 3-DG was significantly enhanced by depletion of GSH, while a decrease in Nrf2-activation by MGO and GO but not 3-DG was observed upon an increase of the cellular GSH levels. Our results reveal subtle differences in the role of GSH in protection against the three typical α-dicarbonyl compounds and in their induction of Nrf2-mediated gene expression, and point at a dual biological effect of the α-dicarbonyl compounds, being reactive toxic electrophiles and -as a consequence- able to induce Nrf2-mediated protective gene expression, with MGO being most reactive.

Dietary advanced glycation endproducts (AGEs) increase their concentration in plasma and tissues, result in inflammation and modulate gut microbial composition in mice; evidence for reversibility.

SCOPE: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown. METHODS AND RESULTS: Young healthy C57BL/6 mice were fed a standard chow (n = 10) or a baked chow high AGE-diet (n = 10) (~1.8-6.9 fold increased protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10 weeks or a switch diet with baked chow for 5 weeks followed by 5 weeks of standard chow (n = 10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10 weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations. CONCLUSION: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.

An in vitro model for microbial fructoselysine degradation shows substantial interindividual differences in metabolic capacities of human fecal slurries.

Fructoselysine is formed upon heating during processing of food products, and being a key intermediate in advanced glycation end product formation considered to be potentially hazardous to human health. Human gut microbes can degrade fructoselysine to yield the short chain fatty acid butyrate. However, quantitative information on these biochemical reactions is lacking, and interindividual differences therein are not well established. Anaerobic incubations with pooled and individual human fecal slurries were optimized and applied to derive quantitative kinetic information for these biochemical reactions. Of 16 individuals tested, 11 were fructoselysine metabolizers, with Vmax, Km and kcat-values varying up to 14.6-fold, 9.5-fold, and 4.4-fold, respectively. Following fructoselysine exposure, 10 of these 11 metabolizers produced significantly increased butyrate concentrations, varying up to 8.6-fold. Bacterial taxonomic profiling of the fecal samples revealed differential abundant taxa for these reactions (e.g. families Ruminococcaceae, Christenellaceae), and Ruminococcus_1 showed the strongest correlation with fructoselysine degradation and butyrate production (ρ ≥ 0.8). This study highlights substantial interindividual differences in gut microbial degradation of fructoselysine. The presented method allows for quantification of gut microbial degradation kinetics for foodborne xenobiotics, and interindividual differences therein, which can be used to refine prediction of internal exposure.