Hierarchical modelling of microbial communities.

SUMMARY: The human body harbours a plethora of microbes that play a fundamental role in the well-being of the host. Still, the contribution of many microorganisms to human health remains undiscovered. To understand the composition of their communities, the accurate genome-scale metabolic network models of participating microorganisms are integrated to construct a community that mimics the normal bacterial flora of humans. So far, tools for modelling the communities have transformed the community into various optimization problems and model compositions. Therefore, any knockout or modification of each submodel (each species) necessitates the up-to-date creation of the community to incorporate rebuildings. To solve this complexity, we refer to the context of SBML in a hierarchical model composition, wherein each species's genome-scale metabolic model is imported as a submodel in another model. Hence, the community is a model composed of submodels defined in separate files. We combine all these files upon parsing to a so-called 'flattened' model, i.e., a comprehensive and valid SBML file of the entire community that COBRApy can parse for further processing. The hierarchical model facilitates the analysis of the whole community irrespective of any changes in the individual submodels. AVAILABILITY AND IMPLEMENTATION: The module is freely available at https://github.com/manuelgloeckler/ncmw.

NCMW: A Python Package to Analyze Metabolic Interactions in the Nasal Microbiome.

The human upper respiratory tract is the reservoir of a diverse community of commensals and potential pathogens (pathobionts), including Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus, which occasionally turn into pathogens causing infectious diseases, while the contribution of many nasal microorganisms to human health remains undiscovered. To better understand the composition of the nasal microbiome community, we create a workflow of the community model, which mimics the human nasal environment. To address this challenge, constraint-based reconstruction of biochemically accurate genome-scale metabolic models (GEMs) networks of microorganisms is mandatory. Our workflow applies constraint-based modeling (CBM), simulates the metabolism between species in a given microbiome, and facilitates generating novel hypotheses on microbial interactions. Utilizing this workflow, we hope to gain a better understanding of interactions from the metabolic modeling perspective. This article presents nasal community modeling workflow (NCMW)-a python package based on GEMs of species as a starting point for understanding the composition of the nasal microbiome community. The package is constructed as a step-by-step mathematical framework for metabolic modeling and analysis of the nasal microbial community. Using constraint-based models reduces the need for culturing species in vitro, a process that is not convenient in the environment of human noses. Availability: NCMW is freely available on the Python Package Index (PIP) via pip install NCMW. The source code, documentation, and usage examples (Jupyter Notebook and example files) are available at https://github.com/manuelgloeckler/ncmw.

Towards the human nasal microbiome: Simulating D. pigrum and S. aureus.

The human nose harbors various microbes that decisively influence the wellbeing and health of their host. Among the most threatening pathogens in this habitat is Staphylococcus aureus. Multiple epidemiological studies identify Dolosigranulum pigrum as a likely beneficial bacterium based on its positive association with health, including negative associations with S. aureus. Carefully curated GEMs are available for both bacterial species that reliably simulate their growth behavior in isolation. To unravel the mutual effects among bacteria, building community models for simulating co-culture growth is necessary. However, modeling microbial communities remains challenging. This article illustrates how applying the NCMW fosters our understanding of two microbes' joint growth conditions in the nasal habitat and their intricate interplay from a metabolic modeling perspective. The resulting community model combines the latest available curated GEMs of D. pigrum and S. aureus. This uses case illustrates how to incorporate genuine GEM of participating microorganisms and creates a basic community model mimicking the human nasal environment. Our analysis supports the role of negative microbe-microbe interactions involving D. pigrum examined experimentally in the lab. By this, we identify and characterize metabolic exchange factors involved in a specific interaction between D. pigrum and S. aureus as an in silico candidate factor for a deep insight into the associated species. This method may serve as a blueprint for developing more complex microbial interaction models. Its direct application suggests new ways to prevent disease-causing infections by inhibiting the growth of pathogens such as S. aureus through microbe-microbe interactions.