Luxembourg researchers develop computer models for hundreds of bacterial strains

 

December 2016

A research team at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg has taken an important step in modelling the complexity of the human gut’s bacterial communities – the microbiome – on the computer. The project, published in Nature Biotechnology, is an example of a study supported by multiple FNR instruments, namely AFR, ATTRACT, CORE and PoC.

Hundreds of different bacterial species live in the human gut, helping us to digest our food. The metabolic processes of these bacteria are not only tremendously important to our health – they are also tremendously complex.

The researchers gathered all known data on the metabolism of 773 bacterial strains – more than ever before. Working from this data, they developed a computer model for each bacterial strain.

AGORA – simulating metabolic processes

This collection, known as AGORA, can now be used on the computer to simulate metabolic processes taking place in the microbes and to investigate how they affect the metabolism of other microbes and that of the human host. The LCSB team published its results in the scientific journal Nature Biotechnology (DOI: 10.1038/nbt.3703) in late November 2016.

The collection of predictive metabolic models is available to researchers via http://vmh.uni.lu.

Human gut bacteria play crucial role in our health

The bacterial species living in the human gut not only help us to digest our food, but also produce valuable vitamins for us and even affect the way we metabolise drugs.

The metabolic processes of these bacteria are crucial to our health, and are highly complex: The bacteria are in constant contact with our gut cells, and the different organisms continually influence one another. Thus, they play as important a role in our health as they do in numerous diseases.

Despite many advances in science, our knowledge of these microbes is still limited.

773 different gut microbes modelled

To improve our understanding and to aid novel discoveries, the research team led by LCSB scientist Prof Dr Ines Thiele, head of the “Molecular Systems Physiology” group and FNR ATTRACT Fellow, has now created the most comprehensive collection of computational models for 773 different gut microbes, capturing their individual metabolisms, called AGORA.

“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. 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.” – FNR ATTRACT Fellow Ines Thiele

Characterising each microbe’s metabolism

The first author of the study, Stefania Magnusdottir, is currently doing her PhD degree in Ines Thiele’s group at the LCSB: “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 characterised 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 personalised 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.” – Stefania Magnusdottir

“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 personalised medicine.” – Co-author Dr Ronan Fleming, leader of the Systems Biochemistry group at the LCSB

AGORA allows for focused experiments

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 modelling of processes within the gut microbes,” – Paul Wilmes

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.”

Funding

The AGORA project has received support from the FNR’s ATTRACT, CORE, Proof-of-Concept (PoC) and AFR funding programmes, as well as from the Advanced Computing program of the US Department of Energy, Offices of Advanced Scientific Computing Research and the Biological and Environmental Research.

Download the publication ‘Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota‘ (Nature Biotechnology)

Prof Dr Ines Thiele, FNR ATTRACT Fellow and Head of the Molecular Systems Physiology group at the LCSB at the University of Luxembourg
Taxonomic and metabolic diversity of the 773 genome-scale metabolic reconstructions. (a) Taxonomic tree of the 773 organisms showing the diversity of the AGORA resource. Colors correspond to the taxonomic classes. The tree was created using GraPhlAn49. (b) Hierarchical clustering of the average ratio of reactions per subsystems found in the reconstructions of the 25 taxonomic classes. The reconstructions are ordered based on phyla and taxonomic classes.

SEE ALSO..

RELATED PROGRAMMES

RELATED HIGHLIGHTS

Spotlight on Young Researchers – revisited 5 years later: A post-PhD life in finance

When Eric Finn Schaanning was featured in Spotlight on Young Researchers in 2017, he had just defended his AFR PhD on fire sales and systemic risk in financial networks at Imperial College London. In 2017, Eric attended the Lindau Nobel Laureate Meeting and in 2018, won an FNR Award for his PhD thesis. 5 years after his PhD, we catch up with Eric, who has been working on cyber risks, financial and regulatory stress tests as well operational risk management – a career spanning Norway, Frankfurt and Zürich – and reflect on the value his PhD has added.

Spotlight on Young Researchers: Improving how industrial plants are engineered

Current engineering systems have an issue: It is fragmented – process, Piping and structural design are carried out by separate teams and involves an error-prone exchange of data. A research collaboration involving public research and industry is tackling this issue by creating a unique central data hub of a plant to which all teams have access, with promising effects on efficiency.

Alpbach Summer School: “You get to experience being a scientist, technician, and engineer in an ESA space mission”

For each edition of the annual two-week Alpbach Summer School, the FNR runs a Call for young science/engineering researchers/students with a connection to Luxembourg to attend. We spoke to participant Crisel Suarez about her experience of the 2022 edition, including how the mission her team developed was awarded “best competitive mission”, and learning what it is like to be a scientist, technician, and engineer in an ESA space mission.

Spotlight on Young Researchers: Understanding the impact climate change has on crop-threatening insects

A type of insect known as whitefly spreads plant viruses and has devastating effects on the vegetables that we depend on and thanks to climate change their negative impact on agriculture is set to increase in the future. Current methods to protect crops depend on delicate relationships between whiteflies and their natural enemies, our crops, and microbial communities, a delicate balance threatened by climate change. Researchers are working with a ‘climate in the lab’ to get a better understanding of what could happen, with the ultimate goal to generate solutions to protect food security.

HistorEsch: 25 objects tell 25 local stories

A temporary exhibition at the Escher Pop-Up-Store takes a different creative approach to storytelling: „HistorEsch: Escher Geschichten a 25 Objeten erzielt” features 25 local stories, told through objects of local residents rather than images. The exhibition is part of the project of FNR ATTRACT Fellow Dr Thomas Cauvin, who works in the field of public history.

“Like a school summer camp, but with amazing young chemists and Nobel laureates”

For each Lindau Nobel Laureate Meeting, the FNR runs a Call for promising young researchers with a connection to Luxembourg to attend. For the 2022 Lindau Meeting, dedicated to chemistry, Adil Kabylda, PhD researcher in the group of Prof Alex Tkatchenko at the University of Luxembourg had this rare opportunity. We speak to Adil about the experience of meeting 30 Nobel laureates and inspiring young scientists.

Spotlight on Young Researchers: Taking disruptions into account in life cycle/sustainability assessment

Global supply networks are more complex than ever, and recent global events have shown how susceptible society is to unpredictable disturbances. Scientists are working to understand the effect disruptions have on the sustainability of productive systems with the goal to provide solutions to support decision-making.

Alpbach Summer School: “I feel very lucky that I was part of this”

For each edition of the annual two-week Alpbach Summer School, the FNR runs a Call for young science/engineering researchers/students with a connection to Luxembourg to attend. We spoke to participant Luca Cressa about this experience of the 2022 edition, including how the mission his team developed was awarded “best science case”.

Spotlight on Young Researchers: Toward a risk assessment system for natural and biological systems

Is it possible to use mathematical indicators to alert about natural disasters and help in the early detection of disease and health issues? Over the past 15 years, scientists have been working on bridging mathematical theory and empirical evidence to do just that. To move the science forward, a key challenge is the underlying mathematical problem, as well as determining how the indicators should be applied.

Spotlight on Young Researchers: Neighbourhood characteristics as determinants of health

Unhealthy lifestyles – unbalanced diet and physical inactivity – are the main factor in the leading cause of death in the world: cardiometabolic disease. Our socioeconomic environment plays a role in these lifestyle choices. Over a 9-year period, researchers are looking at how socio-economic and physical environmental characteristics of residential neighbourhoods shape our physical activity, nutritional behaviour and cardiometabolic health.

This site uses cookies. By continuing to use this site, you agree to the use of cookies for analytics purposes. Find out more in our Privacy Statement