NEW YORK (GenomeWeb) – Researchers at King's College London have tapped Bay area-based biotechnology company Second Genome to provide microbiome profiling services and analysis for participants in the Enquiring About Tolerance (EAT) study, an ongoing initiative to understand eczema and food allergies in children.
The UK's EAT study, which has to date enrolled over 1,000 families, aims to find out whether early introduction of allergenic foods into infants' diets can prevent the development of food allergies further down the road. The researchers are also assessing whether they can use the same approach to prevent the development of other allergic conditions such as asthma, eczema, and hay fever. As part of those efforts, they plan investigate the skin and gut microbiota of more than 300 babies at multiple time points over the course of their first year of life.
Existing research points to a potential relationship between the microbiome and allergies. For example, some studies have shown that reducing microbial exposure early in life results in an increased risk of actopic eczema and allergic disease. However, most research to date has focused on gut bacteria and as such "very little is known about the role of the skin microbiota in this context," according to Carsten Flohr, a physician at St. John's Institute of Dermatology at Guy's and St Thomas' Hospitals and King's College London.
Flohr leads the microbiome aspect of the EAT study. By partnering with Second Genome, his team will have access to the "expertise in and know-how in microbiome profiling to help us understand the role of the gut and skin microbiota in pediatric allergy," he said in a statement. GenomeWeb attempted to speak with a Kings College representative to get more details about the EAT microbiome study but was unable to get a response as of press time.
Kings College will be working with researchers in a division of Second Genome, called Second Genome Solutions, that was established to provide microbiome profiling services and support to external partners. The division offers end-to-end consultation services and tools to clients that cover microbiome study design through to final report and publication. The company also provides customized collection kits that include labelled collection tubes, protocol-specific participant instructions, as well as transportation, and shipping materials. They also offer DNA and RNA isolation services from various sample types among other services.
Through its analysis Second Genome Solutions provides clients with details on the microbial communities present in their samples and how these differ from cases to controls including details about specific strains within species, Second Genome's Chief Business Officer Mohan Iyer told GenomeWeb this week. The company also provides details on the functional potential of the microbiome community including details on what pathways are involved in microbe-human interactions. The company claims to have completed more than 400 microbiome studies for external partners across government and academia, and nutrition and pharmaceutical companies.
As a partner for the EAT study, "What we are doing is incorporating microbiome data into the rest of the [patient] data and figuring out what implication it has in allergies," Iyer said. As part of their efforts, they will profile microbiomes of both the skin and the gut and combine that with other omics information being collected from infants and their families as part of the broader EAT study. It's an opportunity for Second Genome to bring its expertise in the profiling space to bear on a large-scale study. "We can handle this type of scale, we can handle this type of data, and we can integrate the data and get to high-resolution profile for them," he said. "The ability to integrate the metadata with the microbiome really makes the microbiome come alive."
However, microbiome profiling is just one component of the company's broader platform for microbiome-focused drug discovery, Iyer said. By tapping into the growing body of knowledge about interactions between microbial function and human biology, the company hopes to come up with a pipeline of drugs and drug candidates that it can license to pharmaceutical companies or sell to the marketplace.
The company is currently preparing its first drug candidate, a small molecule SGM-1019, for human trials that will test its efficacy in treating cases of inflammatory bowel disease. Earlier this year, Second Genome raised $51 million in two Series B rounds that included participation from SR One, the corporate venture capital arm of GlaxoSmithKline, Pfizer Venture Investments, Roche Venture Fund, and Digitalis Ventures. A portion of those funds will support the planned clinical trials, but they will also be used to expand the company's discovery platform to support indications associated with barrier function, insulin sensitivity, and immune regulation, Second Genome said at the time.
Microbiome profiling is the starting point of the company's discovery platform, Iyer said. "That's where we started as a company and that's the core technology that we've improved over time and employed in drug discovery."
It combines next-generation sequencing technologies with a proprietary microarray chip to offer higher accuracy and resolution of samples as well as more functional and actionable information about the microbiome than simply what species are present. The company uses the PhyloChip assay, which was developed by researchers at Lawrence Berkeley National Laboratory, and measures the relative abundance of more than 50,000 microbial taxa. For its sequencing needs, the company uses Illumina MiSeq.
Informatics is a key component of the company's profiling process, and to that end it has developed proprietary bioinformatics pipeline, called SecondGenomeR, for 16S sequencing that it uses to perform statistical analysis of samples internally and as part of its external projects. These pipelines combine tools such as QIIME and PhyloSeq to perform comparative analyses, multivariate statistical analysis, and data interpretation of microbiome data. The pipeline provides quality statistics on raw sequence, performing phylogenetic or pathway characterization, and highlighting differentially abundant features. It also offers various methods for visualizing and comparing data from samples.
"Microbiome profiling is quite data heavy, much more than a classical human genomics project, because what we are talking about is mixed species genomics," Iyer said. "We can have hundreds of species represented in a sample … and many of the species do not have reference genomes."
But the company has also expanded from just profiling technology to incorporate additional tools for mining the microbiome. Second Genome also believes that its approach to drug discovery is unique in the microbiome space. While some companies focus on using microbes as drugs, the company essentially searches for protein products secreted by the microbes in the human gut in particular that confer some beneficial effect in disease cases, Iyer explained. Some of these microbial proteins have never been identified, made, or characterized, offering a treasure trove of potential drug candidates that have never been studied before, he said.
Using ulcerative colitis as an example, Iyer explained that Second Genome's process starts with extensive microbial profiling of different groups of patients including patients currently suffering a flare, patients not currently dealing with a flare, and healthy patients. "That's the classic starting point for a discovery effort," he said.
The company profiles these samples to understand the makeup of gut bacterial communities and how they change in ulcerative colitis cases. They also look at which transcripts are expressed and in what abundance as well as which proteins are expressed among other bits of information. While some other companies try to develop treatments by profiling communities in fecal samples, "we've been really focused on biopsy samples, so really getting to the particular samples [where] we believe the mechanistic interaction is going on," Iyer said.
Through this process, the company might identify a protein secreted by the gut microbiome that has an anti-inflammatory effect, which could be a potential therapeutic candidate for the disease, Iyer said. The next step would be to do in vitro assays for specific functions such as cytokine release or barrier function or to look at epithelial release. From there, the protein can be moved to in vivo models for additional testing in a more classic drug discovery format.
"[We go] way beyond profiling [to include] in vitro assays and screening assays, in vivo biology, mechanism deconvolution, and then to candidate selection," Iyer said. On the profiling side, in addition to exploring taxonomy and human-microbe interaction mechanisms, "we get to strain-level resolution with fairly high accuracy … which has been fairly hard for most people doing [profiling]."
In addition to healthcare, Second Genome is exploring applications of the microbiome in the ag-bio domain. Last month, it announced that it had inked a research agreement with Monsanto to develop microbiome-based solutions that aim to help farmers better manage environmental challenges on their farms. The multi-year agreement between the two companies includes an option for Monsanto to pursue commercial opportunities resulting from insect-control research in agriculture while Second Genome retains the right to apply discoveries in healthcare and other industries.