Impact of manipulation of glycerol/diol dehydratase activity on intestinal microbiota ecology and metabolism

Abstract

Glycerol/diol dehydratases (GDH) are enzymes that catalyse the production of propionate from 1,2-propanediol, and acrolein from glycerol. Acrolein reacts with dietary carcinogenic heterocyclic amines (HCA), reducing HCA mutagenicity, but is itself also an antimicrobial agent and toxicant. Gut microbial GDH activity has been suggested as an endogenous acrolein source; however, there is limited information on the potential of the intestinal microbiota to have GDH activity, and what impact it can have on the intestinal ecosystem and host health. We hypothesized that GDH activity of gut microbiota is determined by the abundance and distribution of GDH-active taxa and can be enhanced by supplementation of the GDH active Anaerobutyricum hallii, and tested this hypothesis combining quantitative profiling of gdh, model batch fermentations, microbiota manipulation, and kinetic modelling of acrolein formation. Our results suggest that GDH activity is a common trait of intestinal microbiota shared by a few taxa, which was dependent on overall gdh abundance. Anaerobutyricum hallii was identified as a key taxon in GDH metabolism, and its supplementation increased the rate of GDH activity and acrolein release, which enhanced the transformation of HCA and reduced fermentation activity. The findings of this first systematic study on acrolein release by intestinal microbiota indicate that dietary and microbial modulation might impact GDH activity, which may influence host health.

Pathogenic and Commensal Gut Bacteria Harboring Glycerol/Diol Dehydratase Metabolize Glycerol and Produce DNA-Reactive Acrolein

“…Indeed, the potential for GDH metabolism is a common feature of human intestinal microbiota shared by a few taxa including A. hallii, F. plautii, and B. obeum. 28,34 In this study, we found that acrolein was produced by the tested WT S. Typhimurium strains, as revealed by the transformation of the acrolein probe PhIP. The transformation capacity varied over 10-fold for the different strains.…”

“…plautii, and B. obeum. , In this study, we found that acrolein was produced by the tested WT S. Typhimurium strains, as revealed by the transformation of the acrolein probe PhIP. The transformation capacity varied over 10-fold for the different strains.…”

Intestinal permeability and gut microbiota interactions of pharmacologically active compounds in valerian and St. John’s wort

“…The high microbiota to medium ratio was chosen to enable the evaluation of the microbial biotransformation of the compounds and impact of the compounds on microbial viability under limited growth. The nutritive medium was based on the Macfarlane medium for the cultivation of human colon microbiota [20] and contained (in g/L): cellobiose (1); oat xylan (1); larch wood arabinogalactan (1); inulin (0.5); soluble potato starch (1); amicase (3); meat extract (1.5); mucin (4); tryptone (5); yeast extract (4.5); bile salts (0.4); KH 2 PO 4 (3); NaHCO 3 (9) (20); folic acid (20); cyanocobalamin (5); thiamine (50); riboflavin (50); phylloquinone (0,075); menadione (10); pantothenate (100). Single compounds or plant extracts were added to 10 mL microbiota mixture, at a final concentration of 30 µg/mL or 500 µg/mL, respectively.…”

“…In vitro human gut microbiota models inoculated with fecal microbiota and mimicking the physicochemical conditions of the gut are powerful tools to evaluate the xenobiotic-microbiota interactions [10,11]. We previously showed that the artificial microbiota produced with the PolyFermS model inoculated with immobilized fecal microbiota is a reproducible source of large amounts of inocula for high throughput testing and comparison of different treatment conditions, including xenobiotic degradation with the same microbiota background [10,12]. A particular advantage of using the latter is that the amount of inoculum is not limiting and high inoculation ratios (e.g.…”

“…A particular advantage of using the latter is that the amount of inoculum is not limiting and high inoculation ratios (e.g. 80 %) can be used to accurately measure the bioconversion activity of the microbiota without the confounding factor of the microbial growth [10,11,13]. Thus, the biotransformation of xenobiotics can be investigated in this model, as well as the possible impact of xenobiotics on the viability of the artificial colon microbiota and on their SCFAs metabolism.…”