Search

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. [ABSTRACT FROM AUTHOR]

Background: Proanthocyanidins (PAC) and oligosaccharides from cranberry exhibit multiple bioactive health properties and persist intact in the colon post-ingestion. They display a complex bidirectional interaction with the microbiome, which varies based on both time and specific regions of the gut; the nature of this interaction remains inadequately understood. Therefore, we aimed to investigate the impact of cranberry extract on gut microbiota ecology and function. Methods: We studied the effect of a cranberry extract on six healthy participants over a two-week supplementation period using the ex vivo artificial fermentation system TWIN-M-SHIME to replicate luminal and mucosal niches of the ascending and transverse colon. Results: Our findings revealed a significant influence of cranberry extract supplementation on the gut microbiota ecology under ex vivo conditions, leading to a considerable change in bacterial metabolism. Specifically, Bifidobacterium adolescentis ( B. adolescentis ) flourished in the mucus of the ascending colon, accompanied by a reduced adhesion of Proteobacteria . The overall bacterial metabolism shifted from acetate to propionate and, notably, butyrate production following PAC supplementation. Although there were variations in microbiota modulation among the six donors, the butyrogenic effect induced by the supplementation remained consistent across all individuals. This metabolic shift was associated with a rise in the relative abundance of several short-chain fatty acid (SCFA)-producing bacterial genera and the formation of a consortium of key butyrogenic bacteria in the mucus of the transverse colon. Conclusions: These observations suggest that cranberry extract supplementation has the potential to modulate the gut microbiota in a manner that may promote overall gut health., Competing Interests: Desjardins Y holds an NSERC-Symrise Industrial Chair on prebiotic effects of fruit and vegetable (poly)phenols, while the other authors have declared that they have no conflicts of interest., (© The Author(s) 2024.)

Although the relationship between gut microbiota and flavan-3-ol metabolism differs greatly between individuals, the specific metabolic profiles, known as metabotypes, have not yet been clearly defined. In this study, fecal batch fermentations of 34 healthy donors inoculated with (-)-epicatechin were stratified into groups based on their conversion rate of (-)-epicatechin and their quali-quantitative metabolic profile. Fast and slow converters of (-)-epicatechin, high producers of 1-(3'-hydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol (3-HPP-2-ol) and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (3,4-DHPVL) were identified. Fecal microbiota analysis revealed that fast conversion of (-)-epicatechin was associated with short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium spp. and Bacteroides spp., and higher levels of acetate, propionate, butyrate, and valerate were observed for fast converters. Other bacteria were associated with the conversion of 1-(3',4'-dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol into 3-HPP-2-ol ( Lachnospiraceae UCG-010 spp.) and 3,4-DHPVL ( Adlercreutzia equolifaciens ). Such stratification sheds light on the mechanisms of action underlying the high interindividual variability associated with the health benefits of flavan-3-ols.

The development of cardiometabolic (CM) diseases is associated with chronic low-grade inflammation, partly linked to alterations of the gut microbiota (GM) and reduced intestinal integrity. The SINFONI project investigates a multifunctional (MF) nutritional strategy's impact combining different bioactive compounds on inflammation, GM modulation and CM profile. In this randomized crossover-controlled study, 30 subjects at CM-risk consumed MF cereal-products, enriched with polyphenols, fibers, slowly-digestible starch, omega-3 fatty acids or Control cereal-products (without bioactive compounds) for 2 months. Metabolic endotoxemia (lipopolysaccharide (LPS), lipopolysaccharide-binding protein over soluble cluster of differentiation-14 (LBP/sCD14), systemic inflammation and cardiovascular risk markers, intestinal inflammation, CM profile and response to a one-week fructose supplementation, were assessed at fasting and post mixed-meal. GM composition and metabolomic analysis were conducted. Mixed linear models were employed, integrating time (pre/post), treatment (MF/control), and sequence/period. Compared to control, MF intervention reduced intestinal inflammation (fecal calprotectin, p  = 0.007) and endotoxemia (fasting LPS, p  < 0.05), without alteration of systemic inflammation. MF decreased serum branched-chain amino acids compared to control ( p  < 0.05) and increased B.ovatus , B.uniformis , A.butyriciproducens and unclassified Christensenellaceae.CAG-74 ( p  < 0.05). CM markers were unchanged. A 2-month dietary intervention combining multiple bioactive compounds improved intestinal inflammation and induced GM modulation. Such strategy appears as an effective strategy to target low-grade inflammation through multi-target approach.