Advances in Human Microbiome Science

Advances in Human Microbiome Science

Thursday, October 15, 2015

The New York Academy of Sciences

Presented By

Presented by the Microbiome Science Discussion Group at the New York Academy of Sciences

 

The microbiota in the human colon forms one of the densest bacterial ecosystems known in nature. These microbial communities are integrally involved in maintaining numerous functions to keep humans healthy, including regulation of metabolic and immune responses. Imbalances in the microbial ecosystem have been observed in several diseases; this symposium focuses on intestinal diseases including inflammatory bowel disease. It will highlight emerging science that is furthering our understanding of causal relationships between our microbiota and disease as well as applications for human health. This is the first in a series of symposia with subsequent ones to cover impact of microbiota on neurological and metabolic diseases.

This event will also be broadcast as a webinar; registration is required.

Please note: Transmission of presentations via the webinar is subject to individual consent by the speakers. Therefore, we cannot guarantee that every speaker's presentation will be broadcast in full via the webinar. To access all speakers' presentations in full, we invite you to attend the live event in New York City when possible.

Registration Pricing

Member$60
Member (Student / Postdoc / Resident / Fellow)$25
Nonmember (Academia)$105
Nonmember (Corporate)$160
Nonmember (Non-profit)$105
Nonmember (Student / Postdoc / Resident / Fellow)$70

 

Webinar Pricing

Member$30
Student / Postdoc Member$15
Nonmember (Academia)$65
Nonmember (Corporate)$85
Nonmember (Non-profit)$65
Nonmember (Student / Postdoc / Resident / Fellow)$45


Platinum Sponsor

  • Boehringer Ingelheim

The Microbiome Science Discussion Group is proudly supported by


  • Boehringer Ingelheim
  • Pfizer

Agenda

* Presentation titles and times are subject to change.


October 15, 2015

8:30 AM

Registration and Continental Breakfast

9:00 AM

Welcome and Opening Remarks
Sonya Dougal, PhD, The New York Academy of Sciences
John Hambor, PhD, Boehringer Ingelheim

Keynote Address

9:15 AM

Gut Microbiome Richness in Health and Disease
Stanislav Dusko Ehrlich, PhD, Institut National de la Recherche Agronomique (INRA) & King's College London
(Presenter slides will not be included as part of the Webinar broadcast.)

Plenary Session I

10:00 AM

Illuminating the Role of Microbiome in Disease Through Metabolomics
Jonathan Braun, MD, PhD, David Geffen School of Medicine at the University of California, Los Angeles

10:30 AM

Small Molecules from the Human Microbiota
Michael Fischbach, PhD, University of California, San Francisco

11:00 AM

Networking Coffee Break

11:30 AM

Causes and Consequences of Interpersonal Microbial Variation
Andy Goodman, PhD, Yale University School of Medicine

12:00 PM

Diet-Microbiome-Health Interactions in Older People
Paul W. O’Toole, PhD, University College Cork
(Presenter slides will not be included as part of the Webinar broadcast.)

Data-Blitz Presentations

12:30 PM

Quantifying Horizontal Gene Transfer from Metagenomic Sequences
Mingzhi Lin, MS, New York University

12:35 PM

Discordant Temporal Development of Bacterial Phyla and the Emergence of Core in the Fecal Microbiota of Young Children
Tamar Ringel-Kulka, MD, MPH, The University of North Carolina at Chapel Hill
(Presenter slides will not be included as part of the Webinar broadcast.)

12:40 PM

Networking Lunch Break and Poster Session
All poster presenters should stand by their posters 1:00 PM–1:40 PM

Late-Breaking Data Presentations by Young Investigators

1:40 PM

Unintended Consequences of Early-life Antibiotic Administration on the Intestinal Microbiota and Host Immunity
Victoria Ruiz, PhD, NYU Langone Medical Center

1:55 PM

Exploiting the Immune Response to Illuminate Host-microbiota Interactions
Noah Palm, PhD, Yale University School of Medicine

2:10 PM

Group 3 Innate Lymphoid Cells Mediate Intestinal Selection of Commensal Bacteria-specific CD4+ T Cells
Matthew Hepworth, PhD, Weill Cornell Medical College

Plenary Session II

2:25 PM

Metagenomics of the Gut Microbiome: A New Source of Innovative Drugs
Rodolphe Clerval, MS, ENTEROME

2:55 PM

Networking Coffee Break

3:25 PM

Resident Bacterial Induction of IL-10- Mediated Mucosal Immune Homeostasis
R. Balfour Sartor, MD, University of North Carolina School of Medicine
(Presenter slides will not be included as part of the Webinar broadcast.)

3:55 PM

Gene-Environment Interactions Mediate Microbiome Control of Mucosal Immunology
Sarkis Mazmanian, PhD, California Institute of Technology

4:25 PM

Immunologically Relevant Microbiome in IBD-Associated Spondyloarthritis
Randy Longman, MD, PhD, Weill-Cornell Medical College

4:55 PM

Poster Presenter Awards and Closing Remarks
Nilufer Seth, PhD, Pfizer

5:10 PM

Networking Reception and Poster Session

6:00 PM

Adjourn

Speakers

Organizers

Mercedes Beyna, MS

Pfizer

John Hambor, PhD

Boehringer Ingelheim

Dr. John Hambor is currently a Director of Research Beyond Borders at Boehringer Ingelheim where he coordinates a strategic postdoctoral research program focused on developing new therapeutic concepts in collaboration with academic investigators.  Previously, Dr. Hambor was a consultant with the Cell Therapy Group, specializing in stem cell-based drug discovery.  Prior to serving as CEO of CellDesign, a developer of next generation stem cell technologies, he contributed 17 years of research at Pfizer where he identified and validated new drug targets in the areas of inflammation and immunology and developed stem cell-based assays for drug efficacy and safety studies.  Dr. Hambor received both a BA and MS degree in Microbiology from Miami University of Ohio, and earned a PhD in Pathology from Case Western Reserve University, followed by postdoctoral studies at Yale University in the Department of Immunobiology.  He has been an Adjunct Assistant Professor at Connecticut College since 2000 where he teaches Immunology.  He also serves as a member on the board of directors for the Connecticut Veterans Administration Research and Education Foundation and on the advisory committee for the Connecticut Regenerative Medicine Research Fund.

Nilufer Seth, PhD

Pfizer

Nilufer Seth is a scientist in the Emerging Science Group in the Inflammation and Immunology Research Unit at Pfizer.  She received her Ph.D. from Medical College of Augusta in Molecular Biology and Biochemistry.  She then joined the Dana-Farber Cancer Institute for her post-doctoral training where her research focused on the design and development of novel approaches to ex vivo identify and analyze antigen-specific CD4 T cells subsets in human diseases and mouse models of autoimmunity.  She studied antigen specific T cells from HIV and HCV infected individuals as well as in the NOD mouse model of Type 1 Diabetes. She joined the Department of Inflammation and Immunology at Wyeth where she worked on small and large molecule therapeutic programs targeting immune cells and inflammatory cytokines.  Currently at Pfizer she is leading and developing the microbiome strategy, efforts and projects.  Her focus is on developing medicines that will reshape the treatment of inflammatory and autoimmune diseases by harnessing strategies and pathways used by the human gut microbiota to maintain barrier and immune homeostasis.

Erick Young, PhD

Boehringer Ingelheim

Erick R. Young obtained his PhD in synthetic bioorganic chemistry from The Pennsylvania State University and completed post-doctoral studies in natural product synthesis at The Ohio State University.  Upon joining Boehringer Ingelheim Pharmaceuticals in 1998 he served as a small molecule research project leader for immunology & cardiometabolic diseases.  Over time, he became increasingly involved in the generation of new target concepts and championing novel therapeutic modalities for the enablement of new target class space, areas where he has made significant contributions to the BI research strategy & portfolio.  He is currently the Director of External Innovation for the newly formed Research Beyond Borders division of BI where his primary focus is the conception, identification & enablement of new therapeutic mechanisms and disease indications outside the organizations current scope or capabilities.

Sonya Dougal, PhD

The New York Academy of Sciences

Dr. Sonya Dougal serves as the Director of Life Sciences Discussion Groups at the New York Academy of Sciences. In this role, she provides strategic development and oversight of an annual portfolio of scientific workshops on pressing topics across the life sciences and biomedical research. Dr. Dougal has extensive experience in scientific research and program management in academia, industry, and the non-profit sector. She received her bachelor's degree with honors from the University of Massachusetts, Amherst and her PhD in Cognitive Psychology from the University of Pittsburgh. She was the recipient of a Ruth L. Kirschstein National Research Service Award from the National Institutes of Health for her postdoctoral training as a cognitive neuroscientist in the laboratory of Dr. Elizabeth Phelps at New York University.

Speakers

Jonathan Braun, MD, PhD

University of California, Los Angeles

Jonathan Braun is a physician-researcher devoted to the roles of the immune system in resistance and susceptibility to inflammatory bowel disease and cancer. He is a professor and chair of Pathology and Lab Medicine at the David Geffen School of Medicine at UCLA. A native of Cleveland, Ohio, Dr. Braun was raised in Los Angeles, where he focused on violin performance. He was an undergraduate at Stanford University (BS, chemistry and biology), and did his MD and PhD studies at Harvard Medical School with Emil Unanue. After residency in Pathology at Brigham and Women’s Hospital, and a postdoctoral fellowship with David Baltimore at the Whitehead Institute, he joined the faculty at the UCLA School of Medicine in 1985. Through high dimensional biochemical, computational, and genetic methods, his current research addresses the local microbial community, and its impact on chronic mucosal and systemic inflammatory diseases. He has published more than 160 primary research studies, 16 patents, and co-founded three biopharma companies. His past national service includes Chair of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, and President of the Federation of Clinical Immunology Societies. He still plays violin when possible.

Rodolphe Clerval, MS

Enterome

Before joining Enterome, Rodolphe Clerval was VP Corporate and Business Development of TcLand Expression, a molecular diagnostic company. During his tenure with TcLand Expression, he led strategic planning activities and closed several collaborations and licensing deals. Previously he was Business Development Manager at Genzyme. Prior to this he was financial analyst for the brokerage firm Natixis Bleichroeder. Earlier in his career, Rodolphe served as Research Scientist at Aventis Animal Nutrition.

Stanislav Dusko Ehrlich, PhD

King's College London

Stanislav Dusko Ehrlich was trained in Organic Chemistry at the University of Zagreb, Croatia and obtained PhD degree in Biochemistry at the University Paris VII, France. He was a research associate of Dr. Joshua Lederberg, Nobel Prize winner, in the Department of Genetics, Stanford University Medical School, California. He founded and directed Microbial Genetics Research Unit and the Microbiology Division at the National Institute for Agricultural Research (INRA). He is Research Director Emeritus at INRA, where he is the PI of the Metagenopolis project, and Professor at King’s College London, where he is Director of the Centre for Host Microbiome Interactions. He authored or co-authored over 340 publications in peer-reviewed scientific journals, 60 book chapters and 14 patents and holds an H index of 73. He is member of the Croatian Academy of Sciences and Arts, French Academy of Agriculture, the European Molecular Biology Organisation and the American Academy of Microbiology.

Michael A. Fischbach, PhD

University of California, San Francisco

Michael Fischbach is an Associate Professor in the Department of Bioengineering and Therapeutic Sciences at UCSF and a member of the California Institute for Quantitative Biosciences (QB3). Fischbach is a recipient of the NIH Director's New Innovator Award, a Fellowship for Science and Engineering from the David and Lucille Packard Foundation, a Medical Research Award from the W.M. Keck Foundation, a Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award, a Glenn Award for Research in Biological Mechanisms of Aging, and the Young Investigator Grant for Probiotics Research from the Global Probiotics Council. His laboratory uses a combination of genomics and chemistry to identify and characterize small molecules from microbes, with an emphasis on the human microbiome. Fischbach received his Ph.D. as a John and Fannie Hertz Foundation Fellow in chemistry from Harvard in 2007, where he studied the role of iron acquisition in bacterial pathogenesis and the biosynthesis of antibiotics. Before coming to UCSF, he spent two years as an independent fellow at Massachusetts General Hospital coordinating a collaborative effort based at the Broad Institute to develop genomics-based approaches to the discovery of small molecules from microbes. Fischbach is a member of the scientific advisory boards of NGM Biopharmaceuticals, Reckitt Benckiser, Symbiota, and Warp Drive Bio, and a member of Genentech's Scientific Resource Board.

Andy Goodman, PhD

Yale School of Medicine

Andy Goodman completed undergraduate training in Ecology and Evolutionary Biology at Princeton University, and received his Ph.D. in Microbiology from Harvard University. During his postdoctoral studies with Jeffrey Gordon at Washington University, he developed new technologies for manipulating the microbiome at the level of genes, species, and communities. He established his own research group in the Department of Microbial Pathogenesis and Microbial Sciences Institute at Yale University in 2011. The lab combines microbial genetics, gnotobiotics, and computational approaches to dissect the causes and consequences of interpersonal microbial variation.

Matthew R. Hepworth

Weill Cornell Medical College, NYC

Dr. Matthew Hepworth received his PhD in immunology from the University of Manchester, UK and carried out postdoctoral studies at the Humboldt University in Berlin, Germany before joining Weill Cornell Medical College as a Crohn’s and Colitis Foundation of America (CCFA) research fellow at the Jill Robert’s Institute for Research in IBD under the mentorship of Drs. Gregory Sonnenberg and David Artis. His research focus is to employ a combination of basic and translational studies to i) identify novel immunoregulatory pathways that maintain intestinal homeostasis and ii) define which pathways become dysregulated in the context of intestinal inflammation. In 2016 Dr. Hepworth will establish his Wellcome Trust funded-independent laboratory in the United Kingdom.

Mingzhi Lin, MS

New York University

Mingzhi Lin is a graduate student in Edo Kussell’s lab in the Biology Department in New York University. He joined NYU through the Computational Biology program. He is focusing on horizontal gene transfer in bacteria, and working on developing new and powerful approaches to quantify it from genomic and metagenomic sequences. Before joining NYU, he received his undergraduate and master degrees in bioinformatics in Zhejiang University in China. There he worked on network prediction and analysis of protein-protein interactions in plants, and published the first large-scale protein interaction network for Arabidopsis thaliana, the model system for plant.

Randy Longman, MD, PhD

Weill Cornell Medical College

Randy Longman is an Assistant Professor of Medicine and a member of the Jill Roberts Center and Institute for IBD Research at Weill Cornell Medical College (WCMC).  He graduated summa cum laude from Yale University with a B.S./M.S. in Molecular Biophysics and Biochemistry.  He received his medical doctorate from WCMC and his Ph.D. in immunology from The Rockefeller University.  He is an active gastroenterologist and mucosal immunologist focused on basic research to understand the causes and to develop new therapies for inflammatory bowel disease (IBD). The major focus of his research is to define cellular and molecular regulation of innate intestinal barrier immunity and to evaluate the functional implications of IBD-associated microbiota.

Sarkis Mazmanian, PhD

California Institute of Technology

Sarkis K Mazmanian, PhD, is the Louis & Nelly Soux Professor of Microbiology in the Division of Biology & Biological Engineering at the California Institute of Technology (Caltech). He is a Phi Beta Kappa graduate from the University of California, Los Angeles, where Dr. Mazmanian also received his doctoral training in microbiology and immunology studying the mechanism by which Gram-positive pathogens anchor surface protein adhesins during bacterial infection. He was a Helen Hay Whitney Post-doctoral Fellow at Harvard Medical School where he studied how symbiotic bacteria promote healthy maturation of the immune system. He was promoted to assistant professor at Harvard Medical School in 2006, and later that year moved to Caltech. Dr. Mazmanian has won numerous awards including a Searle Scholar, Young Investigator of the Year at Harvard Medical School, Damon Runyon Innovation Award, was named by Discover Magazine as one of the “Best Brains in Science under 40” and recently received the MacArthur Foundation “Genius” award. His laboratory focuses on the study of beneficial bacterial molecules from the human gut microbiome as novel therapies for immunologic and neurologic disorders. He is a founder of 2 biotech companies and serves on the Scientific Advisory Board of over a dozen companies, academic centers and not-for-profit foundations.

Paul O'Toole, PhD

University College Cork

Following industry and academic positions in Sweden, Canada, New Zealand and the US, Paul O’Toole is Professor of Microbial Genomics at University College Cork, Ireland. His main research theme is the genomics of gastrointestinal bacteria in humans with emphasis on commensal species, gut health, IBS, and colorectal cancer. The ultimate aim is to develop novel diagnostics, therapeutics, foods and food ingredients to programme the intestinal microbiota towards promoting health. He co-ordinated ELDERMET (eldermet.ucc.ie), a nationally funded project that established diet-microbiota health interactions in 500 elderly persons, and he leads a project called ELDERFOOD that is investigating dairy-derived foods for healthy aging. He is a Principal Investigator in the Alimentary Pharmabiotic Centre (apc.ucc.ie), leading projects on lactobacillus genomics, and on microbiota in aging, IBS, and colorectal cancer. He leads metagenomics work-packages in the EU FP7 projects NuAge (microbiota in the elderly led by University of Bologna) and MyNewGut, (gut microbiota, diet and behaviour led by CSIC Valencia). As well as national and European agencies, his lab in Cork is also supported by the US NIH (oral microbiome and childhood caries; anchored by NYU). He has published over 150 articles and has an H-index of 39.

Noah W. Palm

Yale University School of Medicine, New Haven, CT

Noah W. Palm is an Assistant Professor of Immunobiology and Human and Translational Immunology at the Yale University School of Medicine. His laboratory focuses on illuminating the myriad interactions between the immune system and the gut microbiota in health and disease. Dr. Palm performed his doctoral work with Dr. Ruslan Medzhitov and his postdoctoral work with Dr. Richard Flavell, both at Yale University.

Tamar Ringel-Kulka, MD, MPH

The University of North Carolina at Chapel Hill

Victoria Ruiz, PhD

NYU Langone Medical Center

Victoria Ruiz is a postdoctoral fellow at New York University School of Medicine in the Division of Translational Medicine in the lab of Dr. Martin Blaser. Her research focuses on the role of early-life antibiotic administration on the gut microbiota and host immunity. She received her Bachelor of Science in Biology from St. John’s University. She received her Ph.D. in Pathobiology from Brown University, where she studied Helicobacter pylori infection and gastric immunopathogenesis.

R. Balfour Sartor, MD

University of North Carolina School of Medicine

Dr. Sartor is a gastroenterologist and mucosal immunologist with a long-standing interest in mechanisms by which commensal microbiota induce chronic intestinal inflammation vs. mucosal homeostasis. Dr. Sartor is the Midgette Distinguished Professor of Medicine at the University of North Carolina (UNC), where he specializes in inflammatory bowel diseases (IBD) and directs the UNC Multidisciplinary IBD Center. Dr. Sartor has been a faculty member at UNC for his entire academic career, where he is the Co-Chief of the Division of Gastroenterology and Hepatology (Research) and Co-Director of the Center for Gastrointestinal Biology and Disease. His research is focused on developing and applying rodent models of chronic, immune-mediated intestinal inflammation relevant to IBD and performing clinically relevant translational studies of IBD patients. Dr. Sartor investigates host genetically programmed immune responses to luminal commensal microbial products using gnotobiotic rodents and patient-derived samples and studies the influence of diet and environmental factors on intestinal microbiota composition and function. He has served as a member and chair of 2 standing NIH Study Sections and Chairman of the Training Awards and Grants Review Committees of the Crohn’s Colitis Foundation of America (CCFA), Chair of the CCFA’s National Scientific Advisory Comm., and a member of the CCFA National Board of Trustees. He is currently the Chief Medical Advisor for the CCFA, Immediate Past Chair of the Immunology, Microbiology and IBD Section of the AGA and Director of the NCRR- funded National Gnotobiotic Rodent Resource Center at UNC. Dr. Sartor has served as the Chair of the Scientific Advisory Committee for the Alberta IBD Consortium since 2009. Dr. Sartor has been continuously funded by the NIH since 1985, has published over 300 peer reviewed scientific manuscripts, review articles and chapters in leading scientific journals such as Nature Medicine, Journal of Clinical Investigation and Gastroenterology, and had edited 5 textbooks, including Kirsner’s Inflammatory Bowel Diseases.

Nilufer Seth, PhD

Pfizer

Nilufer Seth is a scientist in the Emerging Science Group in the Inflammation and Immunology Research Unit at Pfizer.  She received her Ph.D. from Medical College of Augusta in Molecular Biology and Biochemistry.  She then joined the Dana-Farber Cancer Institute for her post-doctoral training where her research focused on the design and development of novel approaches to ex vivo identify and analyze antigen-specific CD4 T cells subsets in human diseases and mouse models of autoimmunity.  She studied antigen specific T cells from HIV and HCV infected individuals as well as in the NOD mouse model of Type 1 Diabetes. She joined the Department of Inflammation and Immunology at Wyeth where she worked on small and large molecule therapeutic programs targeting immune cells and inflammatory cytokines.  Currently at Pfizer she is leading and developing the microbiome strategy, efforts and projects.  Her focus is on developing medicines that will reshape the treatment of inflammatory and autoimmune diseases by harnessing strategies and pathways used by the human gut microbiota to maintain barrier and immune homeostasis.

Sponsors

Platinum Sponsor

  • Boehringer Ingelheim

The Microbiome Science Discussion Group is proudly supported by


  • Boehringer Ingelheim
  • Pfizer

Abstracts

Gut Microbiome Richness in Health and Disease
Stanislav Dusko Ehrlich, PhD, Institut National de la Recherche Agronomique (INRA) & King’s College London

We have developed an approach, named quantitative metagenomics, to assess presence and abundance of microbial genes of the gastrointestinal tract communities. The approach is based on high throughput DNA sequencing in conjunction with an extensive catalog of microbial genes, the latest having >9.9 million genes. A large proportion of the catalog genes encoded by the same microbial species or sub-species genetic elements (viruses, plasmids, CRISPR, etc) have been clustered by an innovative method, based on covariance of gene abundances.  This approach has revealed two types of individuals in populations from Europe, US and Asia, differing by the richness of their gut microbiome. Microbiome poor individuals have a less healthy metabolic and inflammatory profile and an increased risk to develop metabolic syndrome associated chronic diseases, such as diabetes, hepatic & cardiovascular complications. Nutritional interventions can correct, in parallel, metabolic parameters and microbiome richness opening avenues for prevention of chronic diseases. Factors that impact microbial richness will be presented and discussed.

Illuminating the Role of Microbiome in Disease Through Metabolomics
Jonathan Braun, MD, PhD, David Geffen School of Medicine at the University of California, Los Angeles

The composition of the enteric microbiome is increasingly implicated in the threshold and phenotype of local and systemic developmental inflammatory, and neoplastic diseases.  Mechanistically, a simplifying concept is that at-risk microbial communities deleteriously affect host physiology by key bioactive products (primary or secondary small molecules and peptides) they make or fail to make. This concept dictates a shift of microbiome assessment from composition to high-throughput metagenomics, transcription, and metabolomics. It also requires a human systems biology framework, bioinformatically and experimentally, to efficiently screen and validate microbial metabolic candidates that target host traits critical to disease state.  Using such approaches, the landmark bioactive microbial metabolites (short chain fatty acids and secondary bile acids) have been augmented by several new classes of molecules with unexpected host pathophysiologic mechanisms in host traits ranging from mucosal inflammatory disease and autism-like developmental neurobiologic disorders. Microbial communities also organize into one of 3 or 4 modes of metabolic output, termed metabotypes, that may provide a link between environmental and functional states of the microbiome. An important prediction is that pharmacologic targeting of these microbial metabolite pathways may provide a non-ecologic strategy to “treat” the microbiome to improve human health. 

Small Molecules from the Human Microbiota
Michael Fischbach, PhD, University of California, San Francisco

The discovery of natural products – small molecules from microbes often used as drugs – has been an ad hoc pursuit for almost a century. The rapidly growing database of microbial genome sequences offers new opportunities to leverage genomics and bioinformatics toward discovering natural products and characterizing their roles in mediating interspecies interactions. This seminar will describe two convergent, ongoing lines of research: our use of genomics and bioinformatics to identify biosynthetic gene clusters and predict the structures of their small molecule products, and our efforts to identify and characterize small molecules produced by the human microbiota.

Causes and consequences of interpersonal microbial variation
Andy Goodman, PhD, Yale University, New Haven

The human gut provides a habitat for enormous bacterial communities associated with health and resistance to disease. These communities result from a complex process of bacterial cooperation and competition that is not understood. I will describe how new genetic approaches for gut anaerobes can be combined with germfree animal husbandry to identify and characterize inter-bacterial and host-bacterial interactions during health and disease. These approaches shed new light on the balance between invading enteropathogens and resident commensal microbes, revealing new commensal-encoded mechanisms for resilience during inflammation. Mechanistic insights into microbiome dynamics will facilitate predictive and intervention approaches for maximizing the contribution of the microbiome to health.

Diet-Microbiome-Health Interactions in Older People
Paul W. O'Toole, PhD, University College Cork

The fecal microbiota composition of 500 subjects in the ELDERMET cohort differed significantly between individuals; correlated with habitual diet; was directly proportional in diversity to the Healthy Food Diversity index. Gradients in microbiota composition correlated with gradients in several health parameters, after adjustment for possible confounders. Subjects in long-term residential care had the lowest microbiota diversity, and we now show by analysis of microbiota composition over 6 months that a low initial microbiota diversity level is associated with greater composition shift during 6 month follow-up. Residence in a long-term care facility was not required for a low-diversity microbiota, because subjects living in their own homes and consuming a low-diversity diet also acquired a low diversity microbiota. These individuals had lower scores for a number of health parameters. Shotgun metagenome sequencing in 223 subjects indicated that the low diversity microbiota of frailer subjects harbored significantly lower gene counts than the microbiome of subjects consuming a high Healthy Food Diversity index diet, especially for carbohydrate fermentation, amino acid metabolism, and nucleotide metabolism. We also noted differential abundance of sub-groups of a recently discovered order of archaeal methanogens. Application of an iterative bi-clustering algorithm (iBBiG) to microbiota composition data from 732 faecal samples from 371 ELDERMET cohort subjects identified distinctive microbiota configurations associated with ageing in both community and long-stay residential care elderly subjects. These data provide a framework for analysing microbiota-health associations, distinguishing correlation from causation, and developing microbiota-based health surveillance for older adults.

Quantifying Horizontal Gene Transfer from Metagenomic Sequences
Mingzhi Lin, MS, New York University

Microorganisms live in ecologically diverse communities and interact in multiple ways, including horizontal gene transfer (HGT). The biological and evolutionary significance of HGT has broad implications for our understanding of microbial communities, not only in terms of structure, evolution and functions, but also in terms of human health – HGT has been responsible for the dissemination of numerous antibiotic-resistance determinants across diverse bacterial species. Quantification of HGT from microbial sequences sampled from complex environments is thus a critical step to study the impacts of HGT on microbial communities and their interactions with environments, which, however, is still a challenge. To fill this gap, we developed a novel method based on mutational correlation to detect and quantify host- and environment-associated variation of HGT rates from whole-genome shotgun metagenomic sequences. Analysis on samples in human oral cavity from Human Microbiome Project shows HGT rates for some opportunistic pathogens varying widely, even among healthy subjects, with strong niche specialization. Comparing to quantification using genomic sequences, we also observed significantly elevated HGT rates in local microbial communities, underscoring the power of using metagenomic sequences for studying HGT.

Discordant Temporal Development of Bacterial Phyla and the Emergence of Core in the Fecal Microbiota of Young Children
Tamar Ringel-Kulka MD, MPH3#

The colonization pattern of intestinal microbiota during childhood may impact health later in life, but children older than 1 year are poorly studied. We followed healthy children aged 1-4 years (n=28) for up to 12 months, during which a symbiotic intervention and occasional antibiotics intake occurred, and compared them with adults from the same region. Microbiota was quantified with the HITChip phylogenetic microarray and analyzed with linear mixed effects model and other statistical approaches. Synbiotic administration increased the stability of Actinobacteria and antibiotics decreased Clostridium cluster XIVa abundance. Bacterial diversity did not increase in 1-5-year old children and remained significantly lower than in adults. Actinobacteria, Bacilli and Clostridium cluster IV retained child-like abundances, whereas some other groups were converting to adult-like profiles. Microbiota stability increased, with Bacteroidetes being the main contributor. The common core of microbiota in children increased with age from 18 to 25 highly abundant genus-level taxa, including several butyrate-producing organisms, and developed towards an adult like composition. In conclusion, intestinal microbiota is not established before 5 years of age and diversity, core microbiota and different taxa are still developing towards adult type configuration. Discordant development patterns of bacterial phyla may reflect physiological development steps in children.
 
Coauthors: Jing Cheng MSc1,2#, Ineke Heikamp-de Jong4 , Yehuda Ringel MD5,6, Ian Carroll PhD5, Willem M. de Vos PhD1,2,4, Jarkko Salojärvi PhD1 and Reetta Satokari PhD1,2
1 Department of Bacteriology and Immunology, University of Helsinki, Finland
2 Department of Veterinary Biosciences, University of Helsinki, Finland
3 Department of Maternal and Child Health, The University of North Carolina at Chapel Hill
4 Laboratory of Microbiology, Wageningen University, The Netherlands
5 Division of Gastroenterology and Hepatology, The University of North Carolina at Chapel Hill
6 Division of Gastroenterology, Beilinson Hospital, Israel
# Equal contribution

Unintended Consequences of Early-life Antibiotic Administration on the Intestinal Microbiota and Host Immunity
Victoria Ruiz, PhD, NYU Langone Medical Center

Broad-spectrum antibiotics are frequently prescribed for children and in cases of viral infection, provide no clinical benefit. However, early-life antibiotic use may affect the host microbiota, promoting long-term metabolic and immunologic alterations. We hypothesized that early-life therapeutic doses [or pulsed antibiotic treatment (PAT)] would perturb the intestinal microbiota leading to alterations in tissue-specific and systemic immunity. To test this hypothesis, C57BL/6 mice were exposed to the β-lactam, amoxicillin, or the macrolide, tylosin. Therapeutic doses of both agents altered expression profiles of intestinal genes including those involved in lymphocyte function and antimicrobial defenses. Flow cytometric analysis demonstrated that mice exposed to tylosin at day 5 of life had a decreased frequency of specific splenic and ileal T-cell populations, whereas exposure post-weaning had minimal effects. Although even a single tylosin course had multiple immunological alterations in conventional mice, essentially none were detected in germ-free animals; indicating that an antibiotic-perturbed microbiota is required for the observed effects. Transfer of PAT-perturbed microbiota to germ-free recipients led to impaired IgA expression and decreased splenic T cells in the now-conventionalized recipients. Alterations in the frequency of splenic and intestinal T cells and sIgA production were associated with decreased bacterial richness (β-diversity), altered community structure (β-diversity), and microbial compositional changes. These results provide evidence that early-life alterations of the intestinal microbiota by PAT modulate systemic and mucosal cellular and humoral immune phenotypes that may persist long after the exposure has ceased.
 
Coauthors: Thomas Battaglia, Isak Engstrand, Amy Ou, Kenneth H. Cadwell, and Martin J. Blaser, NYU Langone Medical Center

Exploiting the immune response to illuminate host-microbiota interactions
Noah W. Palm, Yale University School of Medicine, New Haven, CT, USA

The composition of the gut microbiota is thought to have dramatic effects on the development and progression of a variety of diseases, including Inflammatory Bowel Disease (IBD), autoimmunity, and metabolic syndrome.  However, identifying the specific bacteria that preferentially affect disease susceptibility and severity in humans remains a major challenge. In response to this problem, we developed a novel technology that uses the host’s own immune response to the microbiota as a guide to identify specific members of the gut microbiota that preferentially modulate disease development. This approach specifically identified known disease-causing intestinal bacteria in a mouse model of microbiota-driven colitis. Furthermore, we were able to use this approach to identify specific bacterial strains from IBD patients that selectively conferred susceptibility to severe colitis when transplanted into germ-free mice. These studies thus: (i) establish a new strategy for the identification of disease- and immune-modulating members of the microbiota in humans; (ii) identify potentially disease-driving members of the intestinal microbiota in humans with IBD; and (iii) begin to establish causal, rather than correlative, connections between specific changes in the microbiota and human disease. Future studies using similar approaches will allow us to elucidate the full spectrum of reciprocal interactions between the microbiota and the host immune system. These studies will lead to a more complete understanding of the role of microbiota composition in human health and disease and will eventually enable the development of novel and specific microbiota-targeted therapeutics.

Group 3 Innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells
Matthew R. Hepworth, Weill Cornell Medical College, NYC, USA

Inflammatory CD4+ T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. While selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells, and that MHCII+ ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. These results define a selection pathway for commensal bacteria-specific CD4+ T cells in the intestine and suggest that this process is dysregulated in human IBD.

Metagenomics of the Gut Microbiome: A New Source of Innovative Drugs
Rodolphe Clerval, MS, ENTEROME

The role of the gut microbiota in the pathogenesis of various disorders is nowadays undisputed. Translation of recent scientific discoveries into healthcare innovation has been limited so far. This is partially attributable to our limited knowledge of the gut microbiota composition and the nature of the complexity of interactions between the microbiome and the host. Modern metagenomic tools, such as whole metagenome sequencing and functional metagenomic screening platforms are opening a new era that will lead to identification of new targets and drug candidates.

Gene-Environment Interactions Mediate Microbiome Control of Mucosal Immunology
Sarkis K Mazmanian, PhD, California Institute of Technology, Pasadena

Advances in genomic technologies have empowered unprecedented analysis of the human genome and the gut microbiome in conditions such inflammatory bowel disease (IBD). Despite a wealth of sequence-based data identifying risk variants in the genome and dysbiosis in the microbiome during IBD, molecular mechanisms unifying gene-microbiome interactions remain unknown. Bacteroides fragilis ameliorates experimental colitis via production of Polysaccharide A, a microbial symbiosis factor delivered to the gut immune system by outer membrane vesicles (OMVs). We reveal herein that OMVs require ATG16L1, a primary IBD-risk gene, to promote regulatory T cell (TREG) activity during protection from colitis. NOD2, a bacterial pattern receptor and the most common gene variant in IBD, interacts with ATG16L1 during clearance of pathogenic gut bacteria. OMVs activate a novel NOD2-ATG16L1 pathway in intestinal dendritic cells that results in anti-inflammatory responses. Finally, immune cells from IBD patients with the T300A risk variant in ATG16L1 do not promote Foxp3+ TREG development OMVs. These findings suggest that variants in ATG16L1 and NOD2 may disrupt ‘sensing’ of the beneficial signals from the gut microbiome, revealing entirely new insights into the etiology of IBD.

Immunology Relevant Microbiome Control of Mucosal Immunology
Randy Longman, MD, PhD

Joint inflammation causes significant morbidity in up to 30% of the 2 million people in the U.S. suffering from inflammatory bowel disease (IBD), but our ability to diagnostically identify, and therapeutically target these symptoms remain limited. IBD-associated joint inflammation or spondyloarthropathy (SpA) is part of a larger group of seronegative SpA with overlapping genetic and clinical features in which the gut is the putative port of entry for microbial triggers of systemic cellular inflammation which ultimately result in joint disease. We have recently shown that specific taxa expand in patients with new-onset rheumatoid arthritis and that intestinal colonization can promote immune cell activation. While several studies have identified marked alterations in the microbiota of patients with inflammatory bowel disease (IBD), the microbial and immune cell contribution to the underlying pathogenesis of IBD-associated SpA (IBD-SpA) remains poorly characterized. This seminar will explore the hypothesis that microbial dysbiosis in IBD-SpA underlies a break in immune tolerance to gut commensals and causes local and systemic expansion of Th17 cells that support joint inflammation.

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