An in vitro model for microbial fructoselysine degradation shows substantial interindividual differences in metabolic capacities of human fecal slurries. (April 2021)

• Record Type: Journal Article
• Authors: van Dongen, Katja C.W.; van der Zande, Meike; Bruyneel, Ben; Vervoort, Jacques J.M.; Rietjens, Ivonne M.C.M.; Belzer, Clara; Beekmann, Karsten
• Is Part Of: Toxicology in vitro. Volume 72(2021)
• Publication Date: 2021-04
• Subjects: Amadori product -- Human gut microbiota -- Interindividual differences -- Michaelis-Menten kinetics -- Short chain fatty acid (SCFA); 13C-3NPH-HCl 13C6-3-nitrophenylhydrazine hydrochloride -- 3NPH-HCl 3-nitrophenylhydrazine hydrochloride -- ADME absorption distribution metabolism excretion -- AGE advanced glycation end-product -- CE collision energy -- EDC N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide -- IS-SCFA 13C isotope labelled derivatized SCFA standard -- ISTD internal standard -- kcat catalytic efficiency -- Km Michaelis-Menten constant -- LDA linear discriminant analysis -- LEfSe LDA effect size -- MRM multiple reaction monitoring -- OTU operational taxonomic unit -- PERMANOVA permutational multivariate analysis of variance -- PBK physiologically based kinetic -- RAGE receptor for advanced glycation end products -- Vmax maximum velocity; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2021.105078
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: 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. Highlights: An in vitro method to quantify human gut microbial degradation kinetic parameters was developed. Gut microbial metabolism of fructoselysine was studied. Large interindividual differences in fructoselysine degradation and resulting SCFA formation Multiple microbial taxa were associated with fructoselysine degradation and SCFA formation. Effective method to quantify metabolic capacity of gut microbiota.