Microbiome-Based Precision Medicine

The microbiome R&D is an emerging area of science that is starting to prove its importance. A PubMed search on the term “human microbiome” yielded 300 citations in 2003, 4,498 citations in 2013, and 24,912 citations in 2016. Basic and applied biomedical research from the Human Microbiome Project and other independent studies prove that a disruption of a stable microbiome ecosystem results in dysbiosis. This imbalance leads to chronic disease and health conditions like inflammation, metabolic disorders, gut disorders, obesity, Type 2 Diabetes, autoimmune disorders, inflammatory bowel disease, neurodevelopmental disorders and more. There is great promise in correlating the microbiome compositions with these diseases and using the microbiome as a tool for therapeutic, diagnostic and product development.

Cambridge Healthtech Institute’s second annual Microbiome-Based Precision Medicine Symposium tracks the scientific and clinical research and applications being made in microbial targeted therapies for inflammation, metabolic disorders, immune disorders and other indications. Through interactive sessions and panel discussions, leading researchers and thought leaders will discuss how their work in this field has and will continue to have tremendous impact in generating personalized diagnostics and therapeutics to improve disease treatment and health maintenance.

Thursday, February 15

7:00 am Registration Open and Morning Coffee

 

MICROBIOME MARKET, STANDARDS, AND LEGAL TRENDS

8:25 Chairperson’s Opening Remarks

Sudeep Basu, Ph.D., Practice Leader, TechVision-Innovation Services, Frost & Sullivan

8:30 Human Microbiome Market Analysis, Trends and Predictions

Sudeep Basu, Ph.D., Practice Leader, TechVision-Innovation Services, Frost & Sullivan

This presentation focuses on microbiome trends including a review of select technologies, markets and products. Additional insights will be provided on the policy and regulatory framework, in the context of the future pipeline - what companies and products are in clinical trials.

9:00 The Microbiome Coalition: Representing Microbiome Companies and Advancing Standards

Mollie Roth, J.D., Executive Director, The Microbiome Coalition (TMBC)

The Microbiome Coalition (TMBC) represents commercial entities in the microbiome space with a mission to promote greater public understanding of the role of the microbiome in human health and wellness and advance appropriate regulation, needed investment and required infrastructure. TMBC is launching a roundtable series on the need for standards around microbiome profiling with the intent to align thinking between companies in a pre-competitive setting to move the needle on standards more rapidly. The issue of the lack of standards around sequencing and how to best profile bacteria in a sample is an urgent issue for the industry.

9:30 The Changing Legal Landscape for Microbiome Research

Joe Kovarik, J.D., Patent Attorney with Bioscience Focus and Shareholder, Sheridan Ross, P.C.
Research and development within the microbiome realm will face three major legal challenges in the next several years — changes in U.S. patent law will drastically impact efforts to protect and enforce intellectual property rights domestically and abroad. This presentation will review the coming changes and challenges and offer insights on how innovators and researchers can best prepare themselves for what’s ahead. 

 

Metabolon 10:00 Precision Metabolomics - Current State and Future Plans 

Luke Miller, Vice President, Ph.D., Lab Operations, Metabolon

Precision Metabolomics™ is an advanced approach with the sensitivity and specificity to accurately measure metabolites at a level that makes an n of 1 study in an individual practicable. At Metabolon, we have put technology and processes in place that are tightly regulated through infrastructure controls, documented SOPs, internal standards and proprietary informatics allowing us to carry out Precision Metabolomics. In this presentation, we discuss our approach and show the importance of Precision Metabolomics.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

 

MICROBIOME ASSOCIATION TO DISEASE

11:15 Microbiome Research at Merck Exploratory Science Center in Cambridge

Grazia Piizzi, Ph.D., Executive Director, Head of Molecular Invention, Merck Exploratory Science Center (ESC)

11:45 Microbiome Association and Role in Gynecologic Cancers

Marina Walther-Antonio, Ph.D., Assistant Professor and Associate Consultant, Department of Surgery and Department of Obstetrics & Gynecology, Microbiome Program, Mayo Clinic
This presentation will review three sets of Our microbiome work towards early detection and predictive microbial biomarkers for endometrial and ovarian cancer will be presented. Our efforts towards the mechanistic investigation of the microbiome role in endometrial cancer will also be covered. In addition, our investigation of the role of the microbiome during ovarian cancer treatment and recurrence in conjunction with the use of Metformin will be shown. Our lab is focused on identifying actionable microbiome dynamics with direct patient translation potential. With that end in mind, we devote a significant part of our efforts to technology development for point-of-care and self-administered diagnostics that empower patient decision making, and microfluidics technologies that are intended to enhance our capacity to detect and treat disease while simultaneously reducing its cost and burden to the patient.

 

DNAnexus 12:15 pm Mosaic, a Cloud-Based Community Platform for the Acceleration of Translational Microbiome Science

Michalis Hadjithomas, Ph.D., Microbiome Lead, DNAnexus

Mosaic provides a collaborative space where researchers can implement and compare microbiome methods through community challenges. The "Strains" series of challenges encourages the improvement of strain-level performance of bioinformatic tools. "Standards" addresses experimental and computational sources of variability in metagenomic analyses to promote accurate and reproducible NGS-based microbiome profiling.

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Session Break

1:55 Chairperson’s Remarks

Bonnie Feldman, D.D.S., MBA, Digital Health Analyst and Chief Growth Officer, DrBonnie360

2:00 Metagenomics of Hospitalized Diarrheal Patients and Healthy Individuals in Kolkata, India

Rita Colwell, Ph.D., Distinguished Professor, Institute for Advanced Computer Studies, University of Maryland

A retrospective case-control study of 65 fecal samples was done that included next-gen sequencing of 45 patients (17 known and 28 unknown disease etiology) and 20 healthy individuals. Metagenomic analyses identified pathogens in samples of known and unknown etiology. This study showed the intestinal microbiome could differentiate healthy, diseased, asymptomatic carriers, and individuals in early stages of disease. Clinical metagenomics potentially will revolutionize diagnostics, prophylactics, and therapeutics of infectious disease.

2:30 A Gut Feeling: Treating Asthma through Microbiome Manipulation

Ricardo Valladares, Ph.D., Director of Research and Development, Siolta Therapeutics

A majority of microbiome-based therapies target gastrointestinal diseases, however what happens in the gut influences the entire body. At Siolta Therapeutics, we are expanding the indications for microbiome-based therapeutics to include airway diseases. Our research and development approach leverages clinical data to rationally design mixed-species bacterial therapeutics for the treatment of airway inflammation. This work is paving the way for clinical trials using our novel mixed-species bacterial therapeutic to address asthma and allergy.

3:00 MVRSION – A New, Sensitive and Economic Method for Species-Level 16S Bacterial Characterization
Seth Crosby, M.D., Director of Scientific Collaboration, Washington University School of Medicine   
16S methods currently employed are, generally, limited to analysis of a single hypervariable region which makes taxonomic classification difficult beyond the genus level without a substantial false positive rate. To address this issue, a novel method, named MVRSION, has been developed to enhance species level calls and abundance estimates through simultaneous analysis and dynamic selection of multiple hypervariable regions.

3:30 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

4:15 NGS and –omics: Towards Understanding Clinical Diseases

Andreas M. Kogelnik, M.D., Ph.D., Director, Open Medicine Institute

4:45 Personalized Nutrition by Prediction of Post-meal Blood Glucose Levels
Tali Raveh-Sadka, Ph.D., Director of Research, DayTwo 
Elevated postprandial (post-meal) blood glucose levels are associated with prediabetes and type II diabetes, but dietary methods for controlling them are lacking. A recent study (Zeevi et al., Cell 2015) showed that postprandial glycemic responses to foods differ greatly across different individuals and can be predicted with high accuracy by an algorithm that uses gut microbiota composition and other personal characteristics. DayTwo provides its clients personalized nutrition recommendations based on this research. Our results indicate that personalized dietary interventions based on this algorithm are effective in both weight loss and in reducing glycated hemoglobin (HbA1c%, a commonly used marker for glycemic control).

5:15 Mining the Human Microbiome for Novel Antimicrobials and Host-Modulators

Jessica Ferreyra, Ph.D., Scientist, NGM Biopharmaceuticals
The molecules produced by the microbiota are play key roles in microbe-host and microbe-microbe interactions and may represent novel targets for therapeutic development. Colonization resistance to microbial pathogens such as C. difficile and Enterobacteriaceae is mediated in part by the microbiota. We have identified human microbiota-derived peptides that exhibit antimicrobial activity against human pathogens. Using two bioinformatics discovery pipelines, we identified 1,204 candidate antimicrobial products from 2,161 microbial genomes of bacteria associated with human gut, mouth, skin and urogenital sites. A subset of 106 candidate antimicrobials were synthesized and tested for in vitro antimicrobial activity against a panel of Gram-negative bacterial pathogens. We identified 24 hits with Gram-negative bacterial inhibitory activity were further characterized these molecules in secondary assays. Two top hits, 5074 and 5223 which were originally identified from the same source bacterial genome, display synergistic activity in MIC assays against multidrug resistant strains of Gram-negative pathogens, including E. coli, K. pneumoniae and A. baumannii as well as in vivo activity in an A. baumannii wound model. We have additionally screened a subset of 84 non-cytotoxic microbiome-derived peptides for the ability to modulate several key host pathways and identified a peptide 5028 which induces cAMP expression in human colon cells. To identify a putative human membrane binding partner responsible for the activity, we screened 5028 in our in-house human membrane receptor deorphanization library and identified a binding partner for 5028. These microbiome-derived molecules represent a starting point for the development of novel therapeutics.

5:45 Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

Friday, February 16

8:00 am Registration Open and Morning Coffee

 

MICROBIOTA AND NEURODEGENERATION

8:25 Chairperson’s Remarks

Bahram Parvin, Ph.D., Director, Biomedical Engineering, University of Nevada, Reno

8:30 The Role of the Microbiota in Neurodegeneration and Prospects for Gene Therapy

Robert Friedland, M.D., Chief, Laboratory of Neurogeriatrics, University of Louisville

Recent research has shown that the gut microbiota have important interactions with the brain. We and others have documented that intestinal microbes may influence neurodegenerative processes through effects on protein misfolding and inflammation. Studies showing a role for the microbiota in Parkinson’s and Alzheimer’s diseases will be reviewed. This is an important new approach to these disorders, as there is currently no effective treatment for the neurodegenerations and there are many ways in which our intestinal microbial populations can be altered (gene therapy targeting the metagenome).

9:00 Microbiome & Neuroscience

Vandana Sampathkumar, PhD, Post-doctoral Scholar, University of Chicago
Despite increasing evidence that the gut microbiome influences neurological health and functioning, little is known about how microbiomes alter the cellular and synaptic organization of neurons. Part of the problem is that many studies focus on the effects of microbiomes on the large and complicated central nervous system (CNS), where finding the putative site(s) of influence remains difficult. In addition, these studies do not address neuronal connectivity changes which is important to find therapeutic targets for the increasing list of pathological neurological conditions as a result of microbiome changes. The enteric nervous system (ENS), often termed the ‘second brain’ being simpler in structure, semi-autonomous and in close proximity to the microbiome can serve as an ideal model system to study neuronal connectivity changes. To date, there is no comprehensive map of the ENS ‘connectome’ in healthy and microbiome free mice. We have developed a multi-scale imaging pipeline that maps the cellular composition of large samples of the ENS (~1 cm3, ~ 1μm resolution) using synchrotron source x-ray microscopy (μXCT) and nanometer reconstructions of neuronal connectivity in the same sample using automated large volume serial electron microscopy (EM) to create unbiased maps of the cellular and synaptic differences in the ENS of wild type (WT) and germ free (GF) mice. Preliminary data already reveals potential cellular, vascular and neuronal changes in the absence of the microbiome. This data will reveal, for the first time, the influence of intestinal microbiota on the normal development of ENS and serve as a model for similar studies of CNS.

9:30 Mind the Intestinal Microbiome in ALS

Jun Sun, PhD, AGA Fellow, Associate Professor, Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago
Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by a progressive death of motor neurons and muscle atrophy. The role of microbiome in ALS remains unclear. We found that changes of the microbiome could be detected in a SOD1 G93A mouse model of ALS before the first signs of the disease. After treated with beneficial bacteria product butyrate, G93A mice exhibited a delayed onset of ALS symptoms and a prolonged life span. This presentation will review recent studies of intestinal inflammation and microbiome in mouse and human ALS.

10:00 A Multiplexed Assay for Microbial Profiling
Bahram Parvin, Ph.D., Director, Biomedical Engineering, University of Nevada, Reno
In some cases, neurological disorders are complemented with a shift in the microbiome. For example, in Alzheimer patients, an association between decreased Firmicutes and Bifidobacterium, and increased Bacteroidetes have been observed in the gut microbiome. The next step is a low-cost and robust assay for a wider epidemiological study and clinical applications. Proposed assay aims to functionalize Buckyballs with fluorescent reporters and nucleic acid sequences to show that a diversity of live microorganisms can be identified. The nucleic acid complexes include an RNA detector, targeting a species-specific sequence in the 16S rRNA, and a complementary DNA with an attached fluorescent reporter. As a result, each bacterium is detected and visualized at a specific emission frequency. To validate the assay, diverse set of microorganisms, with various degrees of cell wall complexities, are selected as model systems. Probes are synthesized to identify several pairs of microorganisms in mixed culture, where efficiency, cross talk, and accuracy of the probe complexes are quantified. Finally, to demonstrate that mixed cultures can be separated and sorted, a microfluidic system is designed that connects a single source-well to multiple sinks. By placing a mixed culture, in the source well, microorganisms can be sorted by their preferred media in the sink wells. The technology allows profiling of bacteria composition, at a very low cost, for eventual translation.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

                                         MICROBIOTA AND DIGESTIVE DISORDERS

11:15 PANEL DISCUSSION: Microbiome and Digestive Disorders – Updates on Current Research and Treatment Options

Moderator: 

George Roche, Founder, Microbiome Meetup; Contributing Writer, Nature Research


Panelists:

Angela Marcobal, PhD, Senior Scientist, Osel, Inc.

Erica D. Sonnenburg, PhD., Senior Research Scientist, Department of Microbiology and Immunology, Stanford University School of Medicine

Neil Stollman MD, AGAF, FACG, FACP, Director, East Bay Center for Digestive Health Research Center; Chairman, Division of Gastroenterology, Alta Bates Summit Medical Center, Oakland; Associate Clinical Professor of Medicine, Division of Gastroenterology, University of California San Francisco; Elected Governor for Northern California, American College of Gastroenterology (ACG)

Additional Panelists to be Announced

12:45 pm Close of Symposium

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