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The Biodiscovery Platform – Case study 1

Our Biodiscovery Platform enables the isolation and investigation of yet unknown microorganisms. These microbes can be used as building blocks for synthetic communities. In this article, we desribe 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

There is increasing interest in developing synthetic microbial communities for answering fundamental questions and developing biotechnological applications. With access to multi-omics technologies and innovations in microbial cultivation, it is possible to predict and experimentally validate metabolic interaction networks and their influence on stability and functioning of synthetic communities. Additionally, 16S rRNA amplicon data analysis procedures can be fine-tuned based on information of candidate strains – such as 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 active contribution of specific strains. This may guide in targeted engineering of bioprocesses. Until now, however, integration of multi-omics approaches to understand and engineer microbial communities and functions has been a major challenge. With in-house expertise in microbial ecology, physiology and genomics, our UNLOCK team can assist in both design and comprehensive 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 microbiome - a case study

At the Laboratory of Microbiology at Wageningen University & Research , we have extensive experience in microbial ecology, physiology and functional (meta)genomics. We have isolated a broad range of novel anaerobic bacteria from diverse ecosystems, one of them being the human gut. A synthetic gut microbiome has recently been designed for reconstructing the central metabolic pathway, unravelling inter-species metabolic interactions and to identify contribution of key gut bacteria to a multitude of functions related to degradation of complex carbon sources and production of short chain fatty acids (SCFA). The knowledge of specific metabolic roles of core gut bacteria can aid in targeted engineering of the human gut microbiome for health benefits.

Approach

We first screened >5000 shotgun metagenomics datasets from public databases to identify highly prevalent core bacterial species in the human gut. We shortlisted 10 core gut bacteria 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. The design was aimed towards efforts to a) reconstruct the central metabolic pathway from diet to SCFA production; b) identify the metabolic basis for co-existence of competing core species; c) identify contributions of each strain to a multitude of functions related to carbohydrate degradation and SCFA production.

Overview of process from data mining to design and investigation of synthetic gut microbiomes for unravelling community stability and functional processes. Figure by Sudarshan Shetty.

Integration of the FAIR Data Platform

The workflow from design to data analysis is shown in the figure above. We carried out metabolite measurements, quantitative microbiota profiling and metatranscriptomics. Three-way integration and identification of key ecological and functional aspects of the synthetic gut microbiome can be achieved through our FAIR Data Platform. The FAIR Data Platform comprises bioinformatics pipelines, which process raw data and generate output for species abundances as well as active gene/pathway abundances that can be further analysed together with metabolite data using our custom workflows provided as Jupyter Notebooks.

Interesting links

Inspired? Read more about our Biodiscovery Platform.

Specifically interested in synthetic and minimal communities as models for the human gut microbiome? Read this publication by a.o. Hauke Smidt, coördinator of the Biodiscovery Platform: 

Sudarshan A Shetty, Hauke Smidt, Willem M de Vos, Reconstructing functional networks in the human intestinal tract using synthetic microbiomes. Current Opinion in Biotechnology, Volume 58 (2019). Pages 146-154. 

 

 

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