By Dana Barberio
June 2, 2016 | Trillions of bacteria dwell in, on, and among us in the oceans, air, soil, plants, and animals, and on May 13, the White House Office of Science and Technology Policy announced its plan to drive research exploring the microbiome. The National Microbiome Initiative (NMI) will invest $121 million to support research on the microbiome across diverse ecosystems, develop technologies to study and share results, and expand the microbiome workforce through citizen science, public engagement, and educational opportunities.
Just as precision medicine has benefited from a multidisciplinary approach, the NMI hopes to encourage an open environment where research and data are shared, not siloed. The National Institutes of Health, the National Science Foundation, Department of Energy, NASA, and the Department of Agriculture will all invest in the effort, and more than 100 outside institutions and groups announced microbiome efforts in conjunction with the NMI.
At the starting point of this massive effort: sample collection.
“The area is ripe for driving innovation across the spectrum, not just from the science perspective, but from a technology perspective,” says Martha Carlin, one of the founders of the BioCollective, who along with the Health Ministries Network announced a $250,000 investment towards building a microbiome data and sample bank, and the engagement of underrepresented groups in microbiome research.
The BioCollective takes a market-based revenue sharing approach to collecting microbiome samples. Interested individuals pay a $90 membership fee, which includes a kit to collect their stool samples at home. Once they send them in, the BioCollective divides, stores, and sells them to interested researchers to accelerate research and discovery in chronic disease, cancer, and obesity.
“As they are sold, the BioCollective shares a percentage of the revenue on the sales to the members who provide the samples,” Carlin explains. BioCollective hopes to eventually provide a percentage of shared revenue from any discoveries leading to intellectual property to all of the members as well.
The BioCollective has plans to collect samples across a broad population, from both diseased and healthy individuals. However, the range of samples needed to understand how the microbiome works in a wide variety of ecosystems is vast. “It’s not just the human microbiome. It’s water, soil, air. We need sampling across the planet. The typical scientific approach to sample collection isn’t going to work on that scale. Addressing these large volumes of samples is one of the challenges” faced in this arena, says Carlin.
Big Micro Data
Large volumes of samples will yield large digital datasets. In a timely publication in Trends in Microbiology (doi: 10.1016/j.tim.2016.02.011) published days after the White House announcement, Nikos Kyrpides and other researchers from the U.S. Department of Energy Joint Genome Institute (DOE JGI) put out a rallying call to found a new National Microbiome Data Center to manage and store the massive amounts of data and metadata that are being accumulated. The intention is to address global challenges in energy, health, agriculture and the environment by providing access to data for large scale comparative analyses.
The favorite tool for these analysis challenges can be found in the field of metagenomics, in which entire microbial communities taken from the environment can be sequenced simultaneously, and then analyzed to determine patterns or signatures that distinguish healthy from unhealthy microbiomes.
One of the pioneers in developing advanced computational approaches and a patented multiplexed ‘barcoded’ next-generation sequencing technology is Metabiomics. The company is focused on developing applications in gastrointestinal disease, autoimmune disease, and metabolic disease.
Greg Kuehn, President and COO of Metabiomics, describes their unique metagenomics-based technology, in which entire microbial communities in hundreds of pooled patient samples are sequenced simultaneously. “The introduction of next generation sequencing has been delivering exponential gains in productivity,” he says. In order to make the sequencing cost-competitive, multiplexing of patient samples was introduced in their patented technology. “The big innovation was the introduction of a short oligonucleotide that is a unique barcode created from DNA for the patient and inserted into the primer used in the sequencing protocol. The barcode (and thus the patient) can be identified after the fact when you are doing bioinformatics analysis,” says Kuehn.
Their technology has been through clinical trials and they are seeking FDA approval for detection ranging from colon polyps through advanced colon adenomas. “Our test is more sensitive to colorectal adenomas than the other non-invasive tests on the market,” says Kuehn. This would come to market as a first line non-invasive screening test, which would be followed up with confirmatory colonoscopies for colon cancer prevention.
Other applications for their technology are in development. “It’s becoming well understood that there are myriad interactions between the microbiome and therapeutic side effects because the microbiome is an incredibly metabolically active community. If the microbiome is out of whack, it can affect how drugs are metabolized, and so it is another factor that you need to control for or take into consideration” during drug development, says Kuehn.
Applying microbiome findings to human health and drug discovery isn’t straightforward, but it is an incredibly rich opportunity.
The microbiome is known to impact our health in myriad ways, helping us digest our food, metabolize drugs and toxins, and ward off disease. While researchers are still trying to understand the mechanisms, dysbiosis—or imbalance—of the human microbiome has been linked to cancer, diabetes (types 1 and 2), inflammatory bowel disease, multiple sclerosis, asthma, allergies, and autism (Genome Medicine; doi: 10.1186/s13073-016-0307-y).
Companies in the microbiome arena are capitalizing on the therapeutic potential of the microbiome by developing their own unique technologies to address the enormous data challenges, through advanced platform technologies and computational analysis that can decipher the complexity of microbial communities.
Evelo Biosciences uses patented computational biology techniques to discover, design and develop bacterial-based therapeutics to tackle cancer treatment through different mechanisms – by activating and priming the immune system and alternatively by disrupting the tumor microenvironment. Another company, Seres Therapeutics, uses novel bioinformatics approaches to help gain an understanding of “keystone” microorganisms and functional pathways that contribute to disease. Based on this knowledge, they design therapeutics using their collection of 9,000 microbial strain isolates derived from healthy human donors. They currently have a candidate in clinical trials for the prevention of Clostridium difficile infection.
As Kyrpides pointed out in the call for a National Microbiome Data Center, though the challenges are significant, "The time is ripe to embark on the greatest endeavor to understand Earth's microbiome.”