Workshop on Next Steps in Studying Human Microbiome and Health in Prospective Studies



Background

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 InitiativeExternal Web Site Policy (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 researchExternal Web Site Policy 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 ProjectExternal Web Site Policy and the European Commission's Metagenomics of the Human Intestinal TractExternal Web Site Policy (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 StandardsExternal Web Site Policy project for metagenomics began and in 2013 the Microbiome Quality Control ProjectExternal Web Site Policy 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 BranchExternal Web Site Policy 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 cancerExternal Web Site Policy.

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.

Purpose

This two-day workshop was sponsored by NCI's Metabolic Epidemiology BranchExternal Web Site Policy in the Division of Cancer Epidemiology and GeneticsExternal Web Site Policy (DCEG) and Epidemiology and Genomics Research Program in the Division of Cancer Control and Population Sciences (DCCPS). It focused on:

The workshop format included opportunities for researchers to hear from public health leadership, interact and explore these topics in breakout sessions, and to network.

Agenda


Day 1 - May 16, 2017
Time Topic
8:00 a.m. Registration Opens
8:30 a.m. - 8:45 a.m.

Welcome and Introduction to the Workshop

Stephen J. Chanock, M.D.
Director, DCEG, NCI

Kathy Helzlsouer, M.D., M.H.S.
Associate Director, EGRP, DCCPS, NCI

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?

Moderator:
Robert N. Hoover, M.D., Sc.D.
Director, Epidemiology and Biostatistics Program, DCEG, NCI

Speakers:
Rob Knight, Ph.D.
Professor, Department of Pediatrics & Department of Computer Science, University of California San Diego

Curtis C. Harris, M.D.
Chief, Laboratory of Carcinogenesis, Center for Cancer Research, NCI

Kathy Helzlsouer, M.D., M.H.S.
Associate Director, Epidemiology and Genomics Research Program, DCCPS, NCI

10:00 a.m. - 10:15 a.m. Break
10:15 a.m. - 11:45 p.m.

Session 2: Collection, Stability, and Quality Control

Moderator:
Curtis Huttenhower, Ph.D.
Associate Professor, Department of Biostatistics, Harvard University

Speakers:
Fecal Collection - Rashmi Sinha, Ph.D.
Senior Investigator, Metabolic Epidemiology Branch, DCEG, NCI

Oral Collection - Emily Vogtmann, Ph.D., M.P.H.
Research Fellow, DCEG, NCI

Quality Controls - Joseph Russell Carmical, Ph.D.
Assistant Professor, Baylor College of Medicine

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

Moderators:
Hera Vlamakis, Ph.D.
Research Scientist, Broad Institute

Owen White, Ph.D.
Professor, Epidemiology and Public Health;
Associate Director, Institute For Genome Sciences;
Director Of The Um Center For Health-Related Informatics And Bioimaging (Chib);
University of Maryland School of Medicine

Speakers:
Microbiome Quality Control Study - Curtis Huttenhower, Ph.D.
Associate Professor, Department of Biostatistics, Harvard University

Shot-Gun Sequencing - Diane Leigh Smith Hutchinson, Ph.D.
Research Associate, Baylor College of Medicine

Automated Provenance Tracking in Microbiome Bioinformatics with QIIME 2 - Greg Caporaso, Ph.D.
Associate Professor, University of Northern Arizona

2:45 p.m. - 3:00 p.m. Break
3:00 p.m. - 5:00 p.m.

Session 4: Statistical Methods

Moderator:
Mitchell H. Gail, M.D., Ph.D.
Senior Investigator, Biostatistics Branch, DCEG, NCI

Speakers:
Biological Variability, Technical Artifacts and Reproducibility in the Study of the Microbiome
Anthony Fodor, Ph.D.
Associate Professor, University of North Carolina at Charlotte

Diversity, Composition and Dynamics in Microbiome Association Studies
Hongzhe Li, Ph.D.
Professor, Perelman School of Medicine, University of Pennsylvania

Replications, Confounding Effects and Overall Contribution of Microbiome in Large Scale Epidemiological Studies
Jianxin Shi, Ph.D.
Senior Investigator, Biostatistics Branch, DCEG, NCI

5:00 p.m.

End of Day 1
Reconvene at 8:15am on May 17, 2017


Day 2 - May 17, 2017
Time Topic
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, Ph.D.
Program Director, Environmental Epidemiology Branch, EGRP, DCCPS, NCI

NCI Intramurally-funded Microbiome Epidemiology Projects – Christian Abnet, Ph.D., M.P.H.
Branch Chief and Senior Investigator, Metabolic Epidemiology Branch, DCEG, NCI

8:45 a.m. - 9:15 a.m.

Martin J. Blaser, M.D.
Muriel and George Singer Professor of Medicine; Professor of Microbiology; Director, Human Microbiome Program, NYU School of Medicine

9:15 a.m. - 10:45 a.m.

Session 6: Collection, Storage/Stability, QC - Cohort Experience

Moderator:
Somdat Mahabir, Ph.D., M.P.H.
Program Director, Environmental Epidemiology Branch, EGRP, DCCPS, NCI

Speakers:
Shanghai Men's and Women's Health Studies - Wei Zheng, M.D., Ph.D., M.P.H.
Co-Leader, Cancer Epidemiology Research Program; Anne Potter Wilson Professor of Medicine; Director, Vanderbilt Epidemiology Center; Vanderbilt-Ingram Cancer Center

Multi-Ethnic Cohort - Loic LeMarchand, M.D., Ph.D.
Professor and Full Member, Epidemiology Program, University of Hawaii Cancer Center and Clinical Professor, John A. Burns School of Medicine, University of Hawaii at Manoa

Adventist Health Study-2 – Michael J. Orlich, M.D., M.P.H.
Assistant Professor, School of Medicine and School of Public Health, Loma Linda University

Health Effects of As Longitudinal Study (HEALS) Cohort - Habibul Ahsan, M.D., MMedSc.
Professor, Department of Public Health Sciences, Department of Medicine; Associate Director, Cancer Research Center, University of Chicago

Nurses Health Studies and Health Professional Follow-Up Study - Andrew T. Chan, M.D., M.P.H.
Associate Professor, Harvard Medical School, Massachusetts General Hospital, and Brighamn and Women's Hospital

10:45 a.m. - 11:00 a.m. Break
11:00 a.m. - 11:45 a.m.

Recommendations from Participants

Break-out sessions
  1. Sample collection, storage, QCs
  2. Sample processing
  3. Statistical analyses

Moderator:
John Michael Gaziano, M.D., M.P.H.
Professor, Harvard Medical School

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

Moderator:
Walter Willett, M.D., Dr.P.H.
Fredrick John Stare Professor of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health

Speakers:
Christian Abnet, Ph.D., M.P.H.
Branch Chief and Senior Investigator, Metabolic Epidemiology Branch, DCEG, NCI

Jacques Ravel, Ph.D.
Professor and Associate Director, Institute for Genome Sciences, University of Maryland

2:00 p.m. – 3:00 p.m.

Closing Panel Session: Human Microbiome and Cancer in Epidemiology Studies: Next Steps

Moderator:
Somdat Mahabir, Ph.D., M.P.H.
Program Director, Environmental Epidemiology Branch, EGRP, DCCPS, NCI

Panelists:
Rashmi Sinha, Ph.D.
Senior Investigator, Metabolic Epidemiology Branch, DCEG, NCI

Heidi Kong, M.D., M.H.Sc.
Investigator, Dermatology Branch, Center for Cancer Research, NCI

Walter Willett, M.D., Dr.P.H.
Fredrick John Stare Professor of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health

3:00 p.m. End of Day 2

Steering Committee

Contact

For further information or questions, contact Somdat Mahabir, Ph.D., M.P.H.