MIT-OpenBiome Translational Microbiome Workshop

November 6, 2015 ~ Sponsored by the MIT Center for Microbiome Informatics and Therapeutics

 

Thank you for a terrific event! View photos of day. 

 

Part I: Welcome and Keynote

1:30 PM: Meet & Greet (snacks provided)

2:00 PM: Welcome!
Eric Alm, PhD, MIT, and Mark Smith, PhD, OpenBiome

2:10 PM: Keynote Presentation
Alan Moss, MD, Beth Israel Medical Center - Clinical trial designs for microbial therapies

 

Part II: Interactive small group discussions

3:00 PM – 4:30 PM

Interactive talks will be given by a variety of speakers working on different aspects of translational microbiome research. Each talk will consist of a ten-minute presentation and a ten-minute discussion. During each time slot, four talks will be given in parallel. Each speaker will speak twice. The talks are organized into themes vital to translation of research into effective therapies. You may choose to attend any talk during each session -- the schedule has been designed to maximize choice.

3:00 - 3:20 PM

Theme 1 (Translational Research at OpenBiome): Elaine Vo, PhD, OpenBiome - The OpenBiome Research Toolkit

Theme 2 (Law & the Microbiome): Carolyn Edelstein, MPA, OpenBiome – Regulating the Microbiome: A public health perspective

Theme 3 (Tools for Interrogating the Microbiome): Nathaniel Chu, MIT - Tools to evaluate best practices in fecal transplantation

Theme 4 (Microbiome Discoveries): Tommi Vatanen, Broad - Testing the hygiene hypothesis: microbiome development of infants with different lifestyles

3:20 - 3:40 PM

Theme 1: Zain Kassam, MD, OpenBiome - The Power of Poop & Public Health: Building the bridge between clinicians & scientists

Theme 2: Rachel Sachs, JD, MPH, Harvard Law School - Patent Law and Microbiome-Based Technologies

Theme 3: Nathaniel Chu, MIT

Theme 4: Tommi Vatanen, Broad

3:40 - 4:00 PM

Theme 1: Elaine Vo, OpenBiome

Theme 2: Rachel Sachs, Harvard Law School

Theme 3: Thomas Gurry, PhD, MIT - A personalized medicine platform for predicting IBD disease recurrence

Theme 4: Sean Kearney, MIT - Intestinal spore-forming commensals competitively outgrow C. difficile in vitro

4:00 - 4:20 PM

Theme 1: Zain Kassam, OpenBiome

Theme 2: Carolyn Edelstein, OpenBiome

Theme 3: Thomas Gurry, MIT

Theme 4: Sean Kearney, MIT

 

Part III: Collaborative problem solving

4:30 – 6:00 PM

Break into inter-disciplinary teams to discuss specific problems facing translation of research into therapeutics and diagnostics. Each team should include at least one representative from MIT, OpenBiome and the clinical research community. Teams will chose topics connected loosely to presentation topics, with discussions targeted towards generating actionable solutions. Speakers will circulate to answer questions and facilitate discussions. Teams will be encouraged to present their solutions to the larger group at the end of the workshop. Pizza and beer will be provided during this session to fuel the discussion.

View the prompts

 

Part IV: Continuing collaborations

6:00 PM into the future

Following the conclusion of the workshop, all attendees are invited to Meadhall at 4 Cambridge Center to continue the dialogue informally. All participants are encouraged to follow-up on new ideas and relationships developed at the workshop to move from discussion into action!

Join the conversation on Twitter using #mitob15

 

MIT-OpenBiome Translational Microbiome Workshop

Problem-Solving Prompts

Select one or more prompts to discuss and brainstorm around with teams of 3-6. Each team should contain at least one member from MIT, OpenBiome and a non-MIT/OpenBiome member at large.

Questions

  1. What degree of phylogenetic resolution is clinically relevant and/or desirable for microbial associations or interventions?
  2. How can we effectively deliver intact microbial strains and communities?
  3. How can we select donors to maximize clinical efficacy of FMT in new indications beyond FMT?
  4. How can OpenBiome safely and sustainably increase the quantity of stool collected to meet the growing clinical need?
  5. How should fecal microbiota for transplantation be regulated?

1. What degree of phylogenetic resolution is clinically relevant and/or desirable for microbial associations or interventions?

Background

Microbiome studies are usually conducted using one of three approaches: qPCR, 16S rRNA and Whole Genome Shotgun (WGS) sequencing. qPCR is cheap and quantitative, but limits itself to a pre-specified set of microbes for which specific primers were designed. 16S rRNA is of medium cost, and is good for identifying the presence and abundance of different taxa, but is limited to the region of the 16S gene being amplified and thus cannot detect differences at the genomic level or minor strain-differences not visible in that sequence. WGS is more expensive, but sequences everything in the sample and therefore yields more information about genomic contents and sequences outside of the 16S gene, while giving a slightly lower but similar level of community coverage to 16S. Alternate approaches can include designing primers for sequence amplicons other than the 16S gene, that allows for more precise identification and quantification of specific strains or specific gene isoforms (e.g. MLST).

Specific questions

  • Do clinical microbiome applications benefit from identification of specific strains at a higher resolution than is available with 16S sequencing?  Is there evidence for this?
  • Do clinical microbiome applications benefit from identification of specific genes and/or gene isoforms in the microbial metagenome?
  • Are there hybrid forms of these technologies or other ‘middle ground’ approaches that could enhance the ability of clinical researchers to identify associations between the microbiome and disease?
  • Are there faster or lower cost tools for achieving these objectives?

Possible resources


2. How can we effectively deliver intact microbial strains and communities?

Background

The efficacy of microbial therapeutics implicitly relies on the delivery of viable cells to their site of action. Current methods in FMT are either invasive or poorly targeted and are likely to compromise the viability of oxygen-sensitive strains. Long term storage is likely to further compromise viability. Furthermore, existing delivery techniques are either highly invasive (e.g. colonoscopy) or poorly targeted (e.g. current capsules/enema). Existing coating technologies rely on a thermo-stable active pharmaceutical ingredients (API). Beyond simply processing samples in an anaerobic chamber and using acid-resistant capsules, what can we do to facilitate the delivery of intact microbial communities?

Possible Resources

People: Elaine Vo, Gina Mendolia, Mark Smith


3. How can we select donors to maximize clinical efficacy of FMT in new indications beyond FMT?

Background

Although FMT from healthy donors is highly effective for the treatment of recurrent C difficile infections, regardless of the healthy donor used, this may not be the case for other indications. In particular, a recent study investigating FMT in UC (Moayeddi, 2015) found that a single donor achieved a 39% efficacy (7/18) while four other donors achieved an aggregate efficacy of 10% (2/20). This suggests that there could be significant heterogeneity in donor efficacy. Given this potential for heterogeneity, we are eager to define best practices in donor selection. Specific clinically desirable components could be metabolites, microbial profiles, or a desirable level of community diversity. There are many open questions regarding best practices in trial design and donor selection.

Specific questions

  • Does it make sense to combine material from multiple donors into a single FMT treatment?
  • How should we select donors for indications for which microbial associations are poorly understood?
  • What type of experimental and/or computational data should we include in this donor selection process?

Possible resources


4. How can OpenBiome safely and sustainably increase the quantity of stool collected to meet the growing clinical need?

Background

OpenBiome’s operations hinge upon receiving regular stool donations from healthy donors. As demand for fecal preparations grows, so too must the amount of stool collected. However, finding eligible donors can be challenging due to OpenBiome’s stringent screening criteria. Of those who expressed interest via the online stool donor registry, the vast majority (97%) were excluded from participation. Once recruited, donating on a regular base can also be challenging, as donors must drop off samples at OpenBiome within 45 minutes of passage.

Specific Questions

  • How can OpenBiome increase the number of donors without compromising safety?
  • How can OpenBiome encourage current donors to increase the number of donations?

Resources


5. How should fecal microbiota for transplantation be regulated?

Background

The regulation of fecal microbiota for transplantation poses a unique challenge, as stool is a complex and variable substance which does not fall neatly into traditional regulatory categories. In the United States, the FDA has chosen to define FMT as an “investigational new drug.”  This designation typically requires that physicians file an investigational new drug application if they intend to use fecal microbiota for treatment or research. However, the FDA has issued “enforcement discretion,” allowing physicians to use FMT without an IND for “C. difficile infection not responding to standard therapy,” while continuing to require that physicians file an IND for use in all other indications.

The current regulatory paradigm in the US poses several challenges. First, it creates uncertainty for practitioners, stool banks and industry, as the future of enforcement discretion remains uncertain. Second, it does not elegantly handle uses for FMT beyond recurrent C. difficile infections. Third, the drug paradigm regulates the stool preparation process, but not the highly variable stool contents.

Internationally, stool is typically regulated as a drug or not regulated at all. Alternative frameworks that have been advanced include regulating stool as a biologic product or a tissue, or creating a hybrid model unique to stool.

Specific questions

  • What regulatory paradigm should be adopted for FMT in the United States to maximize both safety and access?
  • How should the safety of stool contents be assessed?
  • How should the regulatory paradigm vary for different indications, if at all?
  • How should fecal microbiota be regulated at the international level?

Possible resources