Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome

Abstract

The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention.

The microbiome and its pharmacological targets: therapeutic avenues in cardiometabolic diseases

“…The gut ecosystem, as well as its individual members, were shown to contribute to the host metabolism [3] With the increasing number of clinical studies reporting associations between the composition of the gut microbiota and CMD outcomes, one question arises -how are these changes in microbial ecology translated into pharmacological messages to the mammalian host? Consisting of trillions of non-pathogenic bacteria living in a symbiotic relationship with their host, gut microbiota produces several signalling molecules (e.g.…”

Metabolic characterization and viable delivery of Akkermansia muciniphila for its future application

“…By combining previous approaches of modelling interspecies interactions and considering the whole microbiota as one entity, a predictive tool for dietary interventions was created (Shoaie, et al, 2015). The tool, CASINO -Community And Systems-level Interactive and Optimization -predicts dietary interventions based on interactions between the host, the microbiota and the applied diet.…”

“…Finally, CASINO was used to design a beneficial diet for subjects with a poor microbiota composition (Shoaie, et al, 2015).…”

“…The increase in tools for the prediction of multispecies interactions highlights the importance of this application. Moreover, these predictions were instrumental in the prediction of diets to improve the metabolic function of gut microbiota (Shoaie, et al, 2015). Ultimately, this research will lead to increased understanding of the interactions of the gut microbiota and its host, and on its role in gut homeostasis and (dys)function, and it will ultimately pave to way to improve human health using specific gut microbes or dietary interventions.…”

“…Also without the incorporation of immunomodulation in GEMs, it was recently shown that GEMs can be used to design dietary interventions in humans (Shoaie, et al, 2015). As described above, the host diet has influence on the microbial composition and the degradation of dietary components by bacteria has influence on host health.…”