Effects of Betaine and Polydextrose on Intestinal Microbiota and Liver Ergothioneine in a High-Fat Diet-Fed Mouse Model and a Human Colonic Simulation Model

Abstract

<p>Background/Objectives: Ergothioneine (EGT) is an effective antioxidant that animals cannot produce and has an important anti-inflammatory role in cell protection, which can help lower the risk of various diseases. In this study, we investigated the potential role of gut microbiota in the production of EGT, which was found to increase in the mouse liver after dietary supplementation with betaine (BET) or polydextrose (PDX). <br></p><p>Methods: The effects of BET and PDX on the gut microbiota and tissue EGT content were investigated using a diet-induced obese mouse model and simulated fermentation in the human colon. Male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce obesity and related metabolic disorders, and for the last 4 weeks of this study, the mice continued on the same diet, supplemented with BET, PDX, or their combination. The potential function of BET and PDX in microbial EGT production was further studied in an in vitro human colon model. <br></p><p>Results: The quantity of <em>Bifidobacterium</em> spp. and Bacteroidota were significantly higher in the feces of mice on diets supplemented with PDX or BET + PDX, and Enterobacteriaceae levels were significantly higher in PDX-supplemented mice than in HFD-fed mice. Untargeted metabolomic analysis of the liver revealed a significant increase in EGT in mice fed HFDs with BET or BET + PDX. Microbial analysis from samples collected from the human in vitro model showed significant changes in <em>Neglecta timonensis</em>, <em>Blautia faecis</em>, <em>Lachnospiracea incertae sedis</em>, <em>Faecalibacillus</em>, and <em>Stenotrophomonas maltophilia</em> species, along with an increase in microbial metabolites, namely, acetic, propionic and butyric acids, and a decrease in 2-methylbutyric acid. <br></p><p>Conclusions: Although PDX and BET or their combination affected microbial composition and metabolites in the human colon simulation model, the model used was not able to detect a significant change in microbiota-based EGT production and, therefore, could not explain the increase in EGT in the liver of betaine-fed mice.</p>