Taconic Biosciences Microbiome Symposium

On September 29, 2015, Taconic Biosciences hosted the inaugural Advancing Microbiome Research Symposium: Microbiome & Mice at Le Meridien hotel in Cambridge, MA.

This complimentary, full-day symposium featured an agenda with academic and life science industry scientists discussing one of the most exciting topics in life science today, the impact of the microbiome on translational research. The program concluded with a networking and cocktail reception.

Highlights from the Symposium

Scientists presented and discussed how their research has impacted the field of microbiome study and the future direction of their research. Speakers included practical tips for challenging experimental setups, including working with germ-free mice. Topics covered included:

  • How composition of the microbiota affects immune responses
  • How to control for microbiota effects
  • The role of microbiome in disease states, including autoimmune disease and sepsis
  • Differences in microbiota between commercial and academic facilities
  • Impact of Segmented Filamentous Bacteria
  • Specific considerations for working with germ-free animals

Symposium Presentation Topics

  • Impact of microbiota on immune responseDr. Ivaylo Ivanov, Columbia University
    Studying germ-free animals colonized with defined bacterial species helped prove that different components of the intestinal microbiota regulate the balance between pro-inflammatory Th17 cells and regulatory T cells (Treg) in the small intestinal lamina propria. Th17 cells are important mediators of pathogenicity in multiple models of autoimmune inflammation and were induced by certain components of the gut microbiota.
  • The gut immune response in germ-free C57BL/6 mice colonized with a human microbiota Dr. Randi Lundberg, Taconic Biosciences
    Human microbiota-colonized mice are widely used as models for exploring the role of the microbiome in human health and disease. Though the approach has been very effective in identifying causality between certain enterotypes or specific organisms and a disrupted health state, e.g. obesity, the human microbiota-colonized mice are reported to have important limitations. Compared to the human donor material, it has been reported that only around 70% of the taxa on a species level was able to colonize the germ-free murine host, whereas this was 93% for mice colonized with a murine microbiota. In the work presented here, we investigated if altering a common rodent diet to resemble a healthy human diet could enhance the colonization in germ-free mice colonized with human gut microbiota, and in the gnotobiotic offspring. Furthermore, we examined the effect on the immune response.
  • CD4 T cell reconstitution and function after sepsis is modulated by the microbiomeDr. Thomas Griffith, University of Minnesota
    The development of immune suppression after a septic event is well-characterized clinically and is a major reason for increased secondary nosocomial infection and death after sepsis. The composition and functional potential of the naïve CD4 T cell repertoire is asymmetrically affected during sepsis, but the mechanism(s) controlling such changes are unknown. We posited the constituents of the gut flora play an important role in defining the responsiveness of CD4 T cell populations specific for Ag present in the commensal bacterial species that establish polymicrobial sepsis after cecal ligation and puncture (CLP). To test this hypothesis, we tracked the number and function of CD4 T cells specific for an Ag present in the segmented filamentous bacterium (SFB) Candidatus arthromitus in sham- and CLP-treated mice containing or devoid of SFB in their gut.
  • Intestinal microbiota in immune mediated liver injury (IMLI)Dr. James Gorham, University of Virginia
    Using a mouse model of IMLI, the severity of acute hepatic damage varies greatly among mice that are genetically identical, but harbor distinct intestinal microbiota. Probing deeper into mechanism, his lab demonstrated that liver injury following triggering of the death receptor Fas varies greatly as a function of the microbiota. Thus, the status and composition of the intestinal microbiota determine the susceptibility to IMLI, suggesting a model wherein the microbiota acts as a rheostat, actively modulating the extent of liver damage in response to Fas triggering.
  • Mice with a defined flora (three strict obligate anerobes gram positive bacterium): effect of platelet activating factor (PAF)Dr. Edward Carter, Massachusetts General Hospital
    Pure cultures of three obligate anaerobes Gram positive (Clostridium clostridiaformis, Clostridium inoccum, Clostridium sp. ASF 356) were used to colonize the gastrointestinal tracts of germfree Swiss Webster mice. These mice were maintained for 14 months without changes in the defined microbota. Histological examination revealed that the intestines appeared normal. Treatment of these mice with platelet activating factor (PAF) damaged the intestines, increased translocation of the three bacteria to the lymph nodes, but did not cause mortality as it did (100%) in wild type mice. The present data using this new model suggest that intestinal damage per se, sufficient to cause increased bacterial translocation, is not sufficient to cause septic shock and death.
  • Exploiting the immune response to illuminate host-microbiota interactionsDr. Noah W. Palm, Yale University School of Medicine
    The composition of the gut microbiota is thought to have dramatic effects on the development and progression of a variety of diseases, including Inflammatory Bowel Disease (IBD), autoimmunity, and metabolic syndrome. However, identifying the specific bacteria that preferentially affect disease susceptibility and severity in humans remains a major challenge. In response to this problem, we developed a novel technology that uses the host’s own immune response to the microbiota as a guide to identify specific members of the gut microbiota that preferentially modulate disease development. This approach specifically identified known disease-causing intestinal bacteria in a mouse model of microbiota-driven colitis. Furthermore, we were able to use this approach to identify specific bacterial strains from IBD patients that selectively conferred susceptibility to severe colitis when transplanted into germ-free mice.
  • Germ-free mice not only require special care and handling, but also vary from conventional mice across a range of anatomical and physiological parameters. Learn about these unique characteristics as well as some best practices for experiments involving germ-free mice.

View the recordings from this symposium:

   
© 2019 Taconic Biosciences, Inc. All rights reserved.

© 2019 Taconic Biosciences, Inc. All rights reserved.