technologies (e.g., transcriptomics, proteomics, glycomics, metabolomics). Nelson perceives the field as moving away from “just sequencing” toward “integrating all these different -omics approaches.”

In addition to its involvement with the HMP, JCVI itself has about 20 disease-focused metagenomic studies funded not just by NIH but also by the National Science Foundation (NSF), the Bill & Melinda Gates Foundation, the National Aeronautics and Space Administration, and others. For example, the National Institute of Diabetes and Digestive and Kidney Diseases recently awarded JCVI a $5 million grant to study the gut microbiome and virome, along with the urinary proteome and metabolome, in an effort to identify a panel of biomarker candidates for type 1 diabetes. JCVI will be recruiting children with type 1 diabetes and using their healthy siblings as controls. NIH also funded JCVI in collaboration with researchers from New York University to examine how the microbiome and virome change over time in individuals with esophageal cancer. Investigators are following 80 individuals over 4 years; the study is currently entering its final year. Already they have detected microbial signatures associated with different stages of esophageal cancer. It is unclear whether the microbial changes are causing the cancer or the cancer is causing the microbial changes. Either way, Nelson said, “You can imagine new therapies that are based on … restoring what the normal [microbial] population looks like.” A third example of disease-focused JCVI research is a study being conducted in collaboration with Dr. David Brenner at the University of California, San Diego, on liver damage and alcoholism. Using different mouse models, the researchers have demonstrated a correlation between certain changes in microbial metabolites and disease onset (Fouts et al., 2012; Yan et al., 2011).

The Health and Wellness Potential of Microbiome Manipulation

Also at JCVI, Dr. Roger Lasken has created what Nelson described as a “high-throughput pipeline” for generating genomes of microbial species that cannot be cultivated. The methodology is based on cell sorting mechanisms and multiple displacement amplification (MDA). Nelson noted that this type of nontraditional approach is necessary for accessing genomes of the 98 to 99 percent of microbes that cannot be cultivated. As scientists learn more about the role of the microbiome in human health and wellness, accessing that genomic space will become increasingly desirable. Nelson foresees this once-inaccessible genomic information being used to develop novel therapeutic and nutritional (e.g., probiotic) tools in the future.

Yet before the health and wellness potential of microbiome manipulation can be realized, the field faces some key challenges. Nelson identified informatics as one of the “big gaps.” She said, “I think we are getting ahead of ourselves in terms of being able to interpret the data that are be-



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