Simulation and modeling of dietary changes in the infant gut microbiome.

The early gut microbiome is essential for health, and diet has a profound influence in its composition. Oligosaccharides in breast milk or formula act as prebiotics, influencing gut microbiome structure. Here we simulated the impact of a dietary switch from fructooligosaccharides (FOS) to 2-fucosyllactose (2FL) in a continuous culture containing a consortium of species of the infant gut microbiome. During growth on FOS the consortium was dominated by Lactobacillus acidophilus, characterized by high amounts of lactate. Switching to 2FL led to a decrease in total biomass, and a recovery in Bifidobacterium infantis and Escherichia coli levels. While FOS was rapidly metabolized by the consortium, 2FL was utilized only after a delay. 2FL consumption was followed by a gradual switch from lactate to acetate. The activity of these bacterial species correlated well with gene expression analysis. Mathematical modeling of a multi-species consortium in continuous culture was capable to explain in great part the behavior of the system. The model was finally used to represent the outcome of the system after 48 h after each regime. This work highlights the impact of dietary changes in the gut microbiome, and provides a modeling framework to predict this influence.

Anti-inflammatory effect of microbial consortia during the utilization of dietary polysaccharides.

The gut microbiome has a significant impact on host health, especially at the metabolic level. Dietary compounds arriving at the colon have a large influence on the composition of the gut microbiome. High fiber diets have been associated to health benefits that are mediated in great part by short chain fatty acids (SCFA). Gut microbial interactions are relevant for the utilization of complex carbohydrates in the gut microbiome. In this work we characterized the utilization of two dietary polysaccharides by combinations of representative adult gut microbes, and the impact of their activities on a cellular inflammation model. Paired combinations of Bifidobacterium adolescentis, Bacteroides dorei, Lactobacillus plantarum, Escherichia coli and Clostridium symbiosum were grown in inulin or xylan as carbon source. Their relative abundance, substrate consumption and major SCFAs produced were determined. Higher cell growth was observed during inulin consumption, and B. adolescentis and L. plantarum were dominant in co-cultures. The co-culture of B. dorei and C. symbiosum was dominant in xylan. In several cases the combined bacterial growth was lower in co-cultures than monocultures, with a few exceptions of synergistic growth between microorganisms. Inulin fermentation resulted in larger acetate and lactate concentrations, and several combinations grown in xylan containing C. symbiosum were characterized by high amounts of butyrate. These microbial consortia were scaled to batch bioreactor fermentations reaching high cell densities and similar profiles to co-culture experiments. Interestingly, a microbial combination producing high amounts of butyrate was able to reduce IL-8 expression in HT-29 cells co-incubated with TNFα. In summary, this work shows that microbial interactions during the utilization of dietary polysaccharides are complex and substrate dependent. Moreover, certain combinations deploy potent anti-inflammatory effects, which are independent of individual microbial growth, and could be mediated in part by higher butyrate production.