Mathematical modeling of fluid dynamics in in vitro gut fermentation systems: A new tool to improve the interpretation of microbial metabolism

Abstract

In vitro systems are widely employed to assess the impact of dietary compounds on the gut microbiota and their conversion into beneficial bacterial metabolites. However, the complex fluid dynamics and multi‐segmented nature of these systems can complicate the comprehensive analysis of dietary compound fate, potentially confounding physical dilution or washout with microbial catabolism. In this study, we developed fluid dynamics models based on sets of ordinary differential equations to simulate the behavior of an inert compound within two commonly used in vitro systems: the continuous two‐stage PolyFermS system and the semi‐continuous multi‐segmented SHIME® system as well as into various declinations of those systems. The models were validated by investigating the fate of blue dextran, demonstrating excellent agreement between experimental and modeling data (with r2 values ranging from 0.996 to 0.86 for different approaches). As a proof of concept for the utility of fluid dynamics models in in vitro system, we applied generated models to interpret metabolomic data of procyanidin A2 (ProA2) generated from the addition of proanthocyanidin (PAC)‐rich cranberry extract to both the PolyFermS and SHIME® systems. The results suggested ProA2 degradation by the gut microbiota when compared to the modeling of an inert compound. Models of fluid dynamics developed in this study provide a foundation for comprehensive analysis of gut metabolic data in commonly utilized in vitro PolyFermS and SHIME® bioreactor systems and can enable a more accurate understanding of the contribution of bacterial metabolism to the variability in the concentration of target metabolites.

Supplementation with a cranberry extract favors the establishment of butyrogenic guilds in the human fermentation SHIME system

“…Although the luminal and mucosal environments have distinct microbiota profiles, it is worth noting that regional variations along the length of the colon are equally significant. These regional differences can influence how nutrients are metabolized [47] . The M-SHIME system used in the experiments was set up to replicate the conditions of the ascending and transverse colon, as flavan-3-ols monomers and dimers are typically broken down in these specific regions of the colon [15] .…”