Future microbiome studies boosted by ‘multi-omics’ approach
Contributing to a comment piece in Nature, the researchers discuss recent technological advances that are enabling previously unseen detail of the microbiota in the human body.
The use of multi-omics technologies, such as 16S sequencing, metagenomics, metaproteomics and metabolomics, are beginning to yield unique insights into microbiota behaviour.
As well as microbial succession in infant gut maturation, variability in healthy adults, and responses over time to antibiotics and dietary changes, the insights add value in to current knowledge of dysbiotic alterations that are indicative of disease.
Dr Janet Jansson and Dr Erin Baker from the Pacific Northwest National Laboratory detailed a study in which these multi-omics technologies were used to assess the impact of inflammatory bowel disease on the microbiome of a twin cohort.
A range of omics data revealed that certain members of the Firmicutes bacteria group, such as Faecalibacterium prausnitzii, were less plentiful in individuals with ileal Crohn’s disease (ICD) compared to healthy subjects.
Through fermentation these bacteria produce butyrate, a fatty acid known to be important for colonic health.
The metaproteomics data revealed that proteins involved in butyrate production were depleted in patients with ICD. However, metabolite data showed an increase in the bile acids present in stool samples from subjects with ICD.
“Since F. prausnitzii is known to be susceptible to bile acids and low pH, the multi-omics data enabled new hypotheses concerning the role of bile acids in controlling the member composition of the microbiome in the colon and how these relate to patient health,” the authors noted.
“These hypotheses would not have been possible without integration of the different omic results.”
The paper listed a number of bottlenecks that were inherent to current multi-omic studies of complex microbiomes such as the difficulty in extracting molecules from complex sample types such as faecal material.
Other obstacles include the databases required for molecular identifications, and the computational programs and time needed to correlate the multi-omic data.
They acknowledged the strides made in these areas, highlighting recent techniques that allow multiple extractions on a small amount of material in order to collect both the metaproteomic and metabolomic fractions simultaneously.
In addition, the speed of sequencing meant more genomes were being added daily to lessen the problem of molecular identification.
Computational programs and time needed to analyse the output of each omic technology and correlate the data are also increasing rapidly with pathway tools being created to assist in this approach.
“We feel the hard work and investment necessary for better integrated multi-omic analyses is essential for providing novel insight that cannot be gained currently by performing only one or two omic analyses,” they commented.
“We also expect enhanced multi-omic techniques will be capable of performing rapid time course studies and large sample analyses to provide answers to many new and outstanding questions such as disease onset.”
Unified Microbiome Initiative
Jansson and Baker also mentioned a number of international collaborations between the sciences, engineering and other disciplines, such as the Unified Microbiome Initiative (UMI), that would prove crucial in developing the tools and analytical approaches for the future.
The UMI aims to bring together researchers and representatives from public and private agencies and foundations to study the activities of Earth's microbial ecosystems.
The UMI was created to address the two stumbling blocks that prevent the advanced understanding of microbes' role in the biosphere. The fragmentation of the life-sciences field combined with a lack of coordination among the various microbiome research endeavours under way have been identified as the main challenges.
Other initiatives that support collaborative microbiome research include the US Human Microbiome Project, the Canadian Microbiome Initiative, MetaHIT (involving the European Union and China) and the Human Metagenome Consortium in Japan.
Published online ahead of print, DOI: 10.1038/NMICROBIOL.2016.49
“A multi-omic future for microbiome studies.”
Authors: Janet Jansson, Erin Baker