Workshop on Next Steps in Studying Human Microbiome and Health in Prospective Studies
Interest in the role of the microbiome in disease has been increasing in the last year, as evidenced by the May 2016 announcement of the National Microbiome Initiative (NMI), a program which aims to advance microbiome science in order to aid in the development of useful applications in areas such as health care, food production, and environmental restoration. The National Institutes of Health (NIH) is planning to invest $20 million into microbiome research as part of the NMI in fiscal year 2016 and FY2017, with particular emphasis on multi-ecosystem comparison studies and the design of new tools to explore and understand microbiomes. More work needs to be done to understand how to move forward with epidemiologic studies of the human microbiome.
Microbiome studies were put on the map with two major initiatives in 2007 and 2008, respectively: the NIH's Human Microbiome Project and the European Commission's Metagenomics of the Human Intestinal Tract (MetaHIT). Their aim was to generate research resources to enable comprehensive characterization of the human microbiota and to analyze their role in human health and disease.
Since then, a number of studies have been completed that have evaluated best practices for collection methods and efforts to comprehensively evaluate methods for measuring the human microbiome. These include the techniques and protocols for handling human microbiome samples as well as computational pipelines for microbial data processing. The evidence base of experimental data is growing and it may lead to development of consensus on the best methods for collecting biological samples for microbiome analyses. Furthermore, two large initiatives for standardization of DNA extraction and processing have been completed: in 2008 the International Human Microbiome Standards project for metagenomics began and in 2013 the Microbiome Quality Control Project for 16S rRNA sequencing was launched.
However, to date, there have been few epidemiological studies conducted on the role of the microbiome in human health. The standardization of methods necessary for translation to large-scale studies is still in its infancy. Unfortunately, variation at each step in the research pipeline is a concern. Variation may arise from sample collection, storage, DNA extraction, Polymerase Chain Reaction (PCR), DNA sequencing, bioinformatics, and statistical analyses. Drawing inferences from epidemiological studies of the human microbiome will require the replication of findings across multiple populations and, ideally, pooling data from many different cohorts.
To address this gap in research, investigators in the Metabolic Epidemiology Branch of the National Cancer Institute's (NCI) Division of Cancer Epidemiology and Genetics (DCEG) began working to establish cohorts with fecal and oral specimens to prospectively evaluate the association between the human microbiome and cancer risk. They also are pursuing a multi-pronged approach to address microbiome methodologic issues. Learn more about DCEG's research on the human microbiome and cancer.
Additionally, for the past few years, the Epidemiology and Genomics Research Program (EGRP) in NCI's Division of Cancer Control and Population Sciences (DCCPS) has funded a limited number of research projects by extramural investigators on the relation of the human microbiome and certain cancers. EGRP also convened a 2016 Workshop on Research Strategies for Nutritional and Physical Activity Epidemiology and Cancer Prevention. At this meeting emerged the need for a larger group of scientists studying the human microbiome to address critical issues regarding next steps in prospective studies. The efficient characterization of various human microbial ecologies using high-throughput sequencing has the potential to revolutionize research in chronic disease etiology. However, significant methodological challenges must be overcome before valid studies can be conducted in this exciting field.
This two-day workshop was sponsored by NCI's Metabolic Epidemiology Branch in the Division of Cancer Epidemiology and Genetics (DCEG) and Epidemiology and Genomics Research Program in the Division of Cancer Control and Population Sciences (DCCPS). It focused on:
- Bringing together diverse scientists to discuss and seek consensus on optimum methods for collecting oral, fecal, and tissue samples for multi-omics analyses;
- Examining the degree of variation caused by DNA extraction, amplification, sequencing, and bioinformatics methods and the best methods to handle variation in future studies;
- Evaluating the statistical methods for pooling microbiome data from multiple studies;
- Addressing the best types of quality control samples to monitor variation in sample handling between sample batches, studies, and laboratories and which can assess stability during long-term storage; and
- Reporting and data sharing standards for epidemiological studies of the human microbiome.
The workshop format included opportunities for researchers to hear from public health leadership, interact and explore these topics in breakout sessions, and to network.
Day 1 - May 16, 2017
|8:00 a.m.||Registration Opens|
|8:30 a.m. - 8:45 a.m.||
Welcome and Introduction to the Workshop
Stephen J. Chanock, MD
Kathy Helzlsouer, MD, MHS
|8:45 a.m. - 10:00 a.m.||
Session 1: What are the Fundamental Questions that Need to be Addressed in Relation to Microbiome in Health and Dysbiosis?
Curtis C. Harris, MD
Kathy Helzlsouer, MD, MHS
|10:00 a.m. - 10:15 a.m.||Break|
|10:15 a.m. - 11:45 p.m.||
Session 2: Collection, Stability, and Quality Control
Oral Collection - Emily Vogtmann, PhD, MPH
Quality Controls - Joseph Russell Carmical, PhD
|11:45 a.m. - 1:15 p.m.||Lunch|
|1:15 p.m. - 2:45 p.m.||
Session 3: Variation Due to Extraction, Amplification, Sequencing, Bioinformatics & Best Methods for Future Studies
Owen White, PhD
Shot-Gun Sequencing - Diane Leigh Smith Hutchinson, PhD
Automated Provenance Tracking in Microbiome Bioinformatics with QIIME 2 - Greg Caporaso, PhD
|2:45 p.m. - 3:00 p.m.||Break|
|3:00 p.m. - 5:00 p.m.||
Session 4: Statistical Methods
Diversity, Composition and Dynamics in Microbiome Association Studies
Replications, Confounding Effects and Overall Contribution of Microbiome in Large Scale Epidemiological Studies
End of Day 1
Day 2 - May 17, 2017
|8:15 a.m. - 8:45 a.m.||
Session 5: Microbiome-related NCI Extramural/Intramural Grants and Projects
NCI Extramurally-funded Microbiome Epidemiology Grants – Gabriel Lai, PhD
NCI Intramurally-funded Microbiome Epidemiology Projects – Christian Abnet, PhD, MPH
|8:45 a.m. - 9:15 a.m.||
Martin J. Blaser, MD
|9:15 a.m. - 10:45 a.m.||
Session 6: Collection, Storage/Stability, QC - Cohort Experience
Multi-Ethnic Cohort - Loic LeMarchand, MD, PhD
Adventist Health Study-2 – Michael J. Orlich, MD, MPH
Health Effects of As Longitudinal Study (HEALS) Cohort - Habibul Ahsan, MD, MMedSc
Nurses Health Studies and Health Professional Follow-Up Study - Andrew T. Chan, MD, MPH
|10:45 a.m. - 11:00 a.m.||Break|
|11:00 a.m. - 11:45 a.m.||
Recommendations from ParticipantsBreak-out sessions
|11:45 a.m. - 1:15 p.m.||Lunch|
|1:15 p.m. – 2:00 p.m.||
Session 7: Reporting & Data Sharing Standards for Epidemiological Studies of the Human Microbiome
Jacques Ravel, PhD
|2:00 p.m. – 3:00 p.m.||
Closing Panel Session: Human Microbiome and Cancer in Epidemiology Studies: Next Steps
Heidi Kong, MD, MHSc
Walter Willett, MD, DrPH
|3:00 p.m.||End of Day 2|