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Microbiota Therapeutics laboratory PI Dr Varun Aggarwala, FMT, Live Bio-Therapeutics

Microbiota Therapeutics laboratory

The overarching vision of the Microbiota Therapeutics laboratory headed by Dr Varun Aggarwala is to engineer the microbiota for applications in both health and disease.

Our bodies are colonized by symbiotic microorganisms (including bacteria, viruses, fungi) and they have been implicated across several diseases (metabolic, infectious, inflammatory, and neurological), and are exploited therapeutically in both health and disease.

However, several challenges remain: -

1) we have not characterized the vast diversity of our commensal microbes,

2) answered fundamental questions pertaining to their mechanism and modes of action,

3) barely understand the stability and structure of the complex microbial ecology and how it transforms under a homeostatic state and in presence of external perturbations (FMT, dietary changes, probiotics).

This laboratory is addressing these open questions by integrating ideas from computational systems biology, ecology, genomics, & microbial culturing with the eventual aim of engineering microbiota for therapeutics and public health.

Course Facet

In November 2022, the FDA approved a specific C. difficile fecal microbiota treatment under the brand name Rebyota, administered rectally. 

Course Facet

In April 2023, the FDA approved a live spore capsule that can be taken by mouth, under the brand name Vowst.

Course Facet

In the United States, human feces has been regulated as an experimental drug since 2013.

Data Availability

We collaborate extensively with clinicians and work with the longitudinal microbiota samples (both in health and disease, with matched controls) to develop models and test our hypotheses. We live in the golden era of publicly available high-quality genomic datasets and benefit tremendously from repurposing and exploiting independent studies for our investigations.

Projects

Currently, our focus is on microbial transmission -- fecal transplants from donor to recipient, across skin, within families, during communal gatherings -- modeling of bacterial strains, and ecology, to understand the role of specific microbes in health and disease with the goal of identifying candidate strains for precision live bio-therapeutics.

Towards this, we are actively pursuing the following projects in the short term:

  1. Bacterial strain dynamics post Fecal Microbiota Transplants (FMT) for Ulcerative Colitis (UC). 
  2. Microbial Predictors for both clinical endpoint and longevity of response post-FMT for UC.
  3. Identification of super stool donors and superior interventional methodologies by integrating 1000s of FMT.
  4. Pangenomic distribution and stability of commensal microbes, and its impact on engraftment of newer strains from the environment. 
  5. Computational approaches to achieve actionable strain level resolution for commensal microbes.
  6. Core commensal microbiota in early childhood and its impact on the seeding of transient microbes.
  7. FMT registries, donor engraftment (urban vs rural), stool biobanks & hub for Indian microbiota therapeutics.
  8. Engineering of the gut resistome (anti-microbial resistance genes) and FMT. 

Laboratory philosophy and culture 

We have an open non-hierarchical lab culture and encourage critical discussions and respect independent thoughts.

The PI firmly believes that the success of his trainees will the true barometer of his own success and is committed to ensuring a productive environment that will benefit every stakeholder.

The only thing that matters in the lab is the well-being of all members and the positive impact on therapeutics (both directly and indirectly) from every project.

Programme Leadership

Dr. Varun Aggarwala

Dr. Varun Aggarwala

Assistant Professor, Jio Institute

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