The Next Ten Years of Microbiome Research

The Human Microbiome Project's former Program Coordinator, Lita Proctor, set out priorities for the next ten years of human microbiome research in a wide-ranging article for Nature¹. She also provides reflections on the completed Human Microbiome Project that helped jump-start microbiome research in the US and beyond.

In the past ten years microbiome research has consumed more than $1.7B (USD). More than $1B has come from the United States during two phases of the Human Microbiome Project. Findings from the Human Microbiome Project Phase 2 were recently published in Nature. The research outcome has demonstrated the importance of the microbiome in human health from birth and throughout life.

Fundamental Questions Remain Unanswered

While Proctor appreciates the immense volume of research completed, she believes there was too much emphasis on cataloging species names and taxonomy. "We've been characterizing the human microbiome as if it were a relatively fixed property to be mapped and manipulated," she states. "I think that interventions that could help to treat conditions such as diabetes, cancer and autoimmune disease will be discovered only if we move beyond species catalogues and begin to understand the complex and mutable ecological and evolutionary relationships that microbes have with each other and with their hosts."

Proctor points out even with the tremendous amount of discovery from the past decade, many fundamental questions about the human microbiome remain unanswered: What constitutes a normal microbiome, and therefore an impaired or imbalanced one? How does the microbiome differ in different body parts?

Some investigators view and study the microbiome as an organ, yet one of the primary properties of the microbiome is its mutability. The microbiome changes over a lifetime, whereas organs remain largely unchanged. It makes more rapid changes in response to external influences in response to disease. Given this, Proctor "think[s] that the most effective route to discovering microbiome-based remedies will be to establish which microorganisms — and which assemblages of them — play a major part in dictating local conditions, or in affecting important cellular processes".

Supporting the Future of Microbiome Research

Proctor explores two areas that she believes are integral to success in gaining critical insights into the human microbiome:

1. Data Standards

   Data is not analyzed and presented in a standard way, which makes it difficult to reproduce and compare studies. The Genome Standards Consortium has developed standards for reporting metagenomics data and the Data Coordination Center of the HMP has adopted these standards. To move forward, journals and funding agencies must uphold these standards when reporting data, both in databases and publications.

2. Coordination and Collaboration

   As an example of coordination efforts, Proctor notes that twenty-one of twenty-seven NIH Institutes provide extramural funding for human microbiome research. The trans-NIH Microbiome Working Group meets monthly to assure that each institute is aware of new research. Yet, this group has no budget or authority to make funding decisions.

Microbiome research would be better served if there was more formal management and coordination of funding and research. There are thirty-three universities, research institutes, and medical schools that have formal microbiome research centers. Adoption of standards for data analysis and resource sharing could go a long way in advancing knowledge of the human microbiome.

Proctor's outlook for the microbiome is positive and encouraging. She believes better coordination and cross functional research will grow our knowledge faster and allow more to get done with the available funding.

References:

1. Proctor, L. Priorities for the next 10 years of human microbiome research. Nature 569, 623-625 (2019).

2. Aaronson, A. C. et al. Effects of Vendor and Genetic Background on the Composition of the Fecal Microbiota of Inbred Mice. PLoS ONE 10, e0116704 (2015).