2023 Conference Agenda
Monday, April 17, 2023
Mollie Roth, JD, Chairperson, The Annual Translational Microbiome Conference
Microbiota Engraftment, Deep Strain Characterization and Metabolite Profiling: Tools for LBP Design and Development
Traditional live biotherapeutic product (LBP) discovery starts by studying microorganism properties pre-clinically for key phenotypic and genotypic traits. In the clinic, candidate strains are tested for safety first followed by efficacy. This is an expensive and time-consuming process. Starting with a data driven platform, known desirable human phenotypes, like engraftment potential, disease recovery, etc, can be linked to naturally occurring microbial populations. Likewise, deep genomic characterization can be used to narrow strain selection. Insights from discovery cohorts may point to possible application areas for collected strains even before any assays are done. Using advanced bioinformatics, we propose a data-driven approach to discover strains and microbiome derived small molecules for specific application areas. Moreover, MoA, can be hypothesized through comparative genomics analysis. Finally, production potential and safety can be predicted for stain candidates.
Heidi Hau, Ph.D., VP, Scientific Affairs & Partnerships, Clinical Microbiomics
Establishing the 1st WHO International Reference Reagents for Microbiome Analysis
Effective standardisation is essential to translational research and product development. Reference reagents allow for commutability of results across clinical studies and give assurances of quality for manufactured products or diagnostic assays. The MHRA is leading multiple WHO Collaborative Studies to establish a range of reference reagents suitable for standardising microbiome methodologies. These include site-specific DNA and whole-cell reagents for standardisation of NGS, bioinformatics, and DNA extractions. Importantly, we have developed a reporting framework that can be used in conjunction with developed reagents to allow for meaningful interpretation of the results. Here, we will discuss the development of these reagents and present results from the WHO international collaborative study which run throughout 2021 with 23 participants from 11 countries across Asia, Europe, North America and Australia, testing multiple different methodologies and bioinformatics pipelines for shotgun and 16S rRNA amplicon sequencing, establishing the 1st WHO International Reference Reagents for microbiome analysis.
Chrysi Sergaki, Ph.D. , Principal Investigator, Microbiome Group Leader, Medicines & Healthcare Products Regulatory Agency, United Kingdom
The Role of the Gut Microbiome in Explaining Variability in Statin Response
The gut microbiome can impact immune function, inflammation, metabolism, and other factors that contribute to age-related diseases and chronic conditions. Moreover, the gut microbiome can affect drug efficacy, absorption, and toxicity by metabolizing certain drugs and altering their pharmacokinetic. Statins remain one of the most prescribed medications worldwide. While effective in decreasing atherosclerotic cardiovascular disease risk1, statin use is associated with several side effects for a subset of patients, including disrupted metabolic control and increased risk of type II diabetes 2–4. We investigated the potential role of the gut microbiome in modifying patient response to statin therapy. In a cohort of >1840 individuals, we find that the hydrolyzed substrate for the statin target enzyme 3-hydroxy-3-methylglutarate-CoA (HMG-CoA) reductase, HMG, may serve as a reliable marker for statin on-target effects. Through exploring gut microbiome correspondence to blood-derived measures of statin effectiveness and metabolic health parameters among statin users and non-users, we find that heterogeneity in statin response is associated with variation in gut microbiome composition. In particular, a Bacteroides rich, alpha-diversity depleted, microbiome composition corresponds to the strongest statin on-target response, but also greatest disruption to glucose homeostasis, indicating lower treatment doses and/or complementary therapies may be beneficial in these individuals. Our findings suggest a potential path towards personalizing statin treatment through gut microbiome monitoring.
Noa Rappaport, Ph.D., Senior Research Scientist, The Hood-Price Lab for Systems Biomedicine, Institute for Systems Biology
Microbiome Research Supports the Potential for Prevention
In this presentation Dr. Kimes will discuss aspects of clinical development that are moving us from potential to the possible. Additionally, she'll discuss diagnostics support for a targeted approach to microbiome-based interventions.
Nikole Kimes, Ph.D., Founder, Siolta Therapeutics
Modulating the Vaginal Microbiome for Women’s Health and Fertility
The talk will cover an update on the clinical trial of LACTIN-V for recurrent bacterial vaginosis, findings, and post hoc analysis. Also a short update on the FRESH study-South African Women at risk for HIV acquisition, and the FLIP-1 study for women at risk of Preterm birth.
Laurel Lagenaur, Ph.D., Senior Scientist, Osel
A Practical Guide to Microbiome Standards
Microbiome data is being generated at an unprecedented pace. In many cases, a lack of proper controls or comparison to microbiome reference materials means that important and high-impact conclusions cannot be reproduced or reliably compared to similar data sets. Microbiome standards are imperative for microbial community profiling and analysis. Whereas the microbial compositions of experimental samples are variable and often unknown, microbiome standards provide a common, accurate, and consistent measurement as a basis for comparison. In an effort to improve data quality and reproducibility we have developed The Microbiomics Standards and Controls Initiative (M-Sci) to provide well-defined standards and controls free of charge to researchers.
Kris Locken, M.Sc., Microbiome Specialist, Zymo Research Corporation
Presentation to be Announced
Kamlesh Oza, Ph.D., Head, Technical Formulation & Application Services, Evonik
Fundamentals of Nutrition, Diet, and the Gut Microbiome
The diet is a source of microbiota and a source of fuel for the microbiota of the gut microbiome. Gut microbes contribute to human nutrition by increasing nutrient bioavailability, producing nutrients as part of their metabolism, and other mechanisms. Diet is an important, modifiable determinant of the composition and, more importantly, the function of the gut microbiome, supporting the role of nutrition as a key modifiable risk factor for disease. This talk will summarize our current understanding and set the stage for later Nutrition Track talks.
Leigh Frame, Ph.D., Associate Director, Resiliency & Well-Being Center, Program Director, Integrative Medicine, School of Medicine & Health Sciences, George Washington University
The Impact of Diet and Antibiotics on Colorectal Cancer and Immunotherapy: A call for Intervention
From a clinical perspective, an individual’s diet has substantial impacts on the microbiome but current efforts to modify the microbiome to improve health through the use of probiotics have either failed and/or may hinder reconstitution of the microbiome after antibiotic exposure. This has significant impact given the impact of diet and antibiotics on risk for colorectal cancer, which has increased substantially worldwide, especially in the early onset timeframe. We posit that tumor genetic mutations even at very early stages impact the microbiome creating a pro-tumor feedback loop that benefits the tumor but not the host. There is potential for dietary interventions and/or fecal microbiota therapy to slow the emergence of cancer from non-cancer neoplasia in the gut with relevance to both hereditary and sporadic colorectal cancer at all ages. However, indiscriminate use of antibiotics also impact responses to immunotherapy, likely across many tumor types. In order to better understand this interaction, additional investment is needed in pragmatic translational clinical trials to manipulate the microbiome/metabolites to benefit the host to better refine potential preventatives and therapeutic approaches.
Cynthia L. Sears, MD, Bloomberg-Kimmel Professorship of Cancer Immunotherapy, Professor of Medicine, Johns Hopkins School of Medicine
Environmental conditions and lack of nutritional niches often hinder engraftment of new bacteria, whether probiotics or LBPs, into microbiomes. To address this challenge, BCD Bioscience develops novel oligosaccharides that can function as selective prebiotics to support growth of targeted microorganisms. Our proprietary technology breaks down polysaccharides into soluble oligosaccharides from any fiber-rich source material– enabling the creation of countless new prebiotics with unique carbohydrate structures. Here, we present our lead prebiotic fibers and our ongoing work mining their modulation of microbial, metabolic and immune responses. BCD Bioscience is a fiber innovation company that strives to impact health through the microbiome.
Nithya Krishnakumar , Senior Research Associate II, BCD Bioscience
Using Metatranscriptomics and ML to Decipher Host-Microbiome Interactions in Human Health & Disease
RNA is Viome's molecule of choice to decipher human-microbiome interactions for the prevention, early diagnosis, and treatment of chronic diseases. We care not just 'who is there', but also 'what they are doing' from gene expression patterns by sequencing the metatranscriptome. Our bioinformatic pipeline identifies the microbial organisms, microbial gene functions in oral and gut microbiomes, as well as the expressed host genes. Such high complexity data allows us to build ML models to learn and predict response to food nutrients, as well as to classify the disease diagnosis. In this talk, I will present Viome's latest metatranscriptome applications in human health and oral/throat cancer.
Lan Hu, Ph.D., Director, Data Science and Bioinformatics, Viome
Food has the power to heal. Our bodies transform and are transformed by the elements in food and the adage that we are what we eat is figuratively and literally true. Twentieth century nutrition science focused on decoding the building blocks of this transformation -- proteins, fats, carbohydrates, vitamins, and minerals. Twenty-first century nutrition science is aimed at understanding the bioactives that help regulate this transformation -- fibers, phytonutrients, bioactive fats, and ferments. Bioactives regulate nutrient processing in part through the microbiome-mitochondria axis which provides a novel framework for inspiring next-generation nutritional approaches to non-communicable diseases.
Chris Damman, MD, Clinical Associate Professor, University of Washington
Most traditional microbiome studies have been focusing on the relationship between taxonomy and phenotype. The recent development of meta-genomics, meta-transcriptomics, meta-proteomics, metabolomics and AI assisted digitalization tools have enabled a comprehensive digitalized link of central dogma of microbiome and how those blueprints translate into functions. In this talk, we will use examples developed at DSM to demonstrate the state-of-the-art microbiome multi-omics and digitalization development in the nutrition and health fields, especially the discovery of novel biomarkers and MoA models for microbiome modulator products. We will also address the challenges in this field and how we see these exciting collaboration opportunities toward a quantitative “bioprint” of host-microbiome relationship, which will significantly shorten discovery cycle and eventually translate scientific information into precision nutrition solutions for customers.
Frank Xu, Ph.D., Head of Analysis & Strain R&D, DSM Nutritional Products
Dietary interventions may result in individualized or personalized responses in the gut microbiome and are often evaluated through DNA analysis alone. Using longitudinal sampling and simultaneous collection of stool DNA & RNA, combined with multiomic analysis, we explored the impact of intermittent fasting on the gut microbiome. By pairing metatranscriptomics with metagenomics to assess functional and taxonomic composition, we demonstrate the rapidity of microbial gene expression changes potentially impacting host-microbiome interactions.
Brice Le Francois, Ph.D., Senior R&D Manager - Technology, DNA Genotek