The Biodiscovery Platform

Our Biodiscovery Platform enables the isolation and investigation of yet unknown microorganisms. Subsequently, these microbes can be used as building blocks for synthetic microbial communities. In this article, we describe the design of a synthetic microbial community from a source of microbes we always carry with us: the human gut.

By the Biodiscovery Platform / July 14, 2021

KEY MESSAGES

The understanding and application of synthetic microbial communities become increasingly popular. It can, however, be challenging.
By combining the different expertises within our UNLOCK team, we can accelerate the design and characterization of synthetic communities.
Eventually, the design of a synthetic community representing the human gut microbiome will lead to better understanding. Ultimately, this may help to improve human health.

Currently, there is increasing interest in developing synthetic microbial communities. These communities could pave the way to answers to fundamental questions and the development of biotechnological applications. In fact, with current access to multi-omics technologies it is possible to predict metabolic interaction networks and their influence on stability and functioning of synthetic communities. Next, with innovations in cultivation of microbes, these predictions can be experimentally validated. Complementarily, 16S rRNA amplicon data analysis procedures can be fine-tuned based on information of candidate strains. For instance, such information could be the number of 16S rRNA gene copies per genome and custom databases with known copies of 16S rRNA gene sequences. Moreover, application of (meta)transcriptomics and (meta)proteomics can help identify the actual active contribution of specific microbial strains. All in all, this may guide in targeted engineering of bioprocesses.

The role of UNLOCK

Until now, however, integration of multi-omics approaches to understand and engineer microbial communities and functions has been a major challenge. Our UNLOCK team, luckily, has in-house expertise in the field of microbial ecology, physiology and genomics, which can assist in both design and the characterization of synthetic microbial communities for researchers. Furthermore, we can predict, validate and optimize the contribution of individual strains to functional traits within the community.

A synthetic gut microbial community - a case study

At the Laboratory of Microbiology at Wageningen University & Research, which is affiliated with UNLOCK, we have extensive experience in microbial ecology, physiology and functional (meta)genomics. For instance, we have isolated a broad range of novel anaerobic bacteria from diverse ecosystems. One of these is a source we all carry: the human gut. As a result, a synthetic gut microbiome has recently been designed. Subsequently, this community may help to reconstruct the metabolic pathways from diet to metabolite. It may also unravel metabolic interactions between microbial species. Additionally, it may assist in identifying the contribution of key gut bacteria to different functions related to degradation of complex carbon sources and subsequent production of short chain fatty acids (SCFA). The knowledge on specific metabolic roles of key gut bacteria can eventually aid in targeted engineering of the human gut microbiome. Finally, this could lead to benefits for human health.

Approach

First, we screened over 5000 shotgun metagenomics datasets from public databases to identify highly prevalent core bacterial species in the human gut. Next, we shortlisted 10 core gut bacteria. We did this by using a combination of genome-based prediction; in silico metabolic network-based predictions of competition and complementarity; and the available information on the physiology of core bacteria. In brief, the design was aimed towards efforts to

Firstly, reconstruct the central metabolic pathway from diet to SCFA production,
Secondly, identify the metabolic basis for co-existence of competing core species,
Lastly, identify contributions of each microbial strain to multiple functions related to degradation of carbohydrates and production of SCFA

An overview of the process from datamining to design and investigation of synthetic gut microbiomes, which helps unravelling community stability and function. Figure by Sudarshan Shetty.

Integration of the FAIR Data Platform

In summary, we carried out metabolite measurements, quantitative microbiota profiling and metatranscriptomics. Subsequently, three-way integration and identification of key ecological and functional aspects of the synthetic gut microbiome can be achieved through our FAIR Data Platform. This platform comprises bioinformatics pipelines, which process raw data and generate output for species abundances as well as active gene/pathway abundances. This output can be further analysed together with metabolite data using our custom workflows provided as Jupyter Notebooks. For the whole workflow, see the figure above.

Interesting links

If you got inspired, read more about our Biodiscovery Platform.

When you are interested in synthetic and minimal communities as models for the human gut microbiome, read this publication by a.o. Hauke Smidt, manager of the Biodiscovery Platform: