Research

Characterizing the Microbiome of Dysbiosis

Disturbances of the intestinal microorganisms can compromise the health of the host. Persistent imbalanced states that lead to disease are referred to as dysbioses. Several patterns of dysbiosis have been associated with particular diseases. However, we are still a long way from being able to definitely conclude that certain patterns of bacteria are always (or often) associated with a particular condition. Our research focus is to characterize these patterns from a variety of diseases to understand which features might be mechanistically linked to a particular pathology.

Human Microbiota Associated Mouse Model

Humanized mouse modelMicrobiology has historically been linked to clinical outcomes through the germ theory of disease and Koch's postulates, where pathogenic microorganisms can be identified, cultured, and tested to confirm their roles in communicable diseases. However, the recent attention to microbiome research primarily concerns the association of gut bacteria with non-communicable diseases like obesity, inflammatory bowel diseases, and cancers. This creates a need for a new model to confirm and test the role of microbial communities, many of the members of which cannot be cultured and have uncharacterized physiology. Our group is attempting to address this need using a human microbiota associated mouse model. This model allows engraftment of human intestinal microbiota at similar levels to that in germ-free mice and provides a novel platform to test host-microbe interactions in a translational animal model.

Research Projects

We collaborate with a wide variety of highly motivated physician scientists, and our on-going research projects include:

The Microbiome and Obesity

  • Characterizing a continuum of dysbiotic states associated with obesity
  • Determining causal mechanisms of the microbiota using human microbiota-associated mouse model

The Microbiome in Cancer

  • Using human microbiota-associated mouse models to understand tumor-microbiome interactions
  • Evaluating how treatments for acute leukemia and stem cell transplantation disrupt the microbiome and compromise the intestinal barrier

Fecal Microbiota Transplantation

  • Optimizing encapsulated fecal microbiota preparations to treat:
    • Recurrent Clostridium difficile infections
    • Inflammatory bowel diseases
    • Obesity

 

Recent Publications

  • Rashidi A, Maeser D, Kaiser T, Ebadi M, Rehman TU, Holtan SG, Weisdorf DJ, Khoruts A, Staley C. 2020. British Journal of Haematology. Microbiome swings with repeated insults. doi:10.1111/bjh.16509
  • Rashidi A, Herman A, Staley C, Blazer BR, Weisdorf DJ. 2019. British Journal of Haematology. An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease. doi:10.1111/bjh.16458
  • Rashidi A, Kaiser T, Graizer C, Holtan SG, Rehman TU, Weisdorf DJ, Dunny G, Khoruts A, Staley C. 2019. Cancer. Gut dysbiosis during anti-leukemia chemotherapy versus allogeneic hematopoietic cell transplantation. in press
  • Rashidi A, Zhigang G, Kaiser T, Manias DA, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Dunny GA, Staley C. 2019. PloS One. Vancomycin-resistance gene cluster, vanC, in the gut microbiome of acute leukemia patients undergoing intensive chemotherapy. 14(10), e0223890 doi:10.1371/journal.pone.0223890
  • Staley C, Kaiser T, Vaughn BP, Graizig C, Hamilton MJ, Kabage AJ, Khoruts A, Sadowsky MJ. 2019. mBIO. Durable long-term bacterial engraftment following encapsulated fecal microbiota transplantation to treat Clostridium difficile. 10(4), e01586-19 doi:10.1128/mBio.01586-19
  • Rashidi A, Kaiser T, Graizer C, Holtan SG, Rehman TU, Weisdorf DJ, Khoruts A, Staley C. 2019. Leukemia. Specific gut microbiota changes heralding bloodstream infection and neutropenic fever during intensive chemotherapy. doi:10.1038/s41375-019-0547-0