Digital Microbes Could Give More Insight into Gut Health

30 Nov 2016 --- A research team at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg has created a computer model of the complex microbiome, gathering all known data on the metabolism of 773 bacterial strains. They hope the data will allow them to simulate the metabolic processes taking place in the microbes.

The computer model collection, known as AGORA, can also be used to investigate how microbes affect the metabolism of other microbes and that of the human host.

Prof. Dr. Ines Thiele, head of the "Molecular Systems Physiology" group, says: "AGORA is based on a new concept for the comparative reconstruction of bacterial metabolic models.”

"It allows the analysis of a much greater number of bacterial strains than was ever possible before.”

She continues, “With AGORA, and by including other datasets, we can systematically study the metabolic interactions within the gut microbiome and how these interactions are influenced by external factors, including the diet and host metabolism."

The first author of the study, Stefania Magnusdottir, adds, "The basis for our paper was a thorough investigation of the literature on microbial metabolism," she explains.

"We gathered known experimental and genomic data on the metabolism of 773 bacterial strains to refine and validate the computational models. Based on this, we characterized each microbe's metabolism and found that both their metabolic capabilities and our diet play important roles in how the microbes interact with each other.”

“We can generate personalized microbiome models by integrating these computational models with metagenomic data, which can be obtained by sequencing the microbes present in stool samples of healthy and sick individuals."

Co-author Dr. Ronan Fleming, who leads the Systems Biochemistry group at the LCSB, adds, “With our models, we can search, in a targeted manner, for metabolic pathways that are fundamentally important to the microbiome in the gut, and we can work out what could trigger diseases when these metabolic processes go wrong."

“The AGORA models will now allow us to study the impact of host-microbiome interactions in specific diseases or to use them in the emerging field of personalized medicine."

Using AGORA to study the gut microbiome will involve close collaboration with researchers who are investigating the gut microbiome in the laboratory, including Prof. Dr Paul Wilmes, head of the LCSB Eco-Systems Biology group. His group has developed methods for studying gut bacteria under real-life conditions.

"AGORA directs us to targeted bacterial metabolic processes to perform focused experiments, allowing precise and comprehensive modeling of processes within the gut microbes," Wilmes asserts.

For Ines Thiele, the high degree of precision is not an end in itself.

"We want to understand how the microbes modulate human metabolism when we modify our diet. This may give us clues as to how we may prevent, or even treat, diseases, for example by identifying dietary supplements that could modify the interactions within a diseased gut microbiome to imitate the metabolic functions of a healthy one.”