Understanding the Role of Gut Microbiome in Pathogenesis of Clostridioides Difficile Infection

Clostridioides difficile is a leading cause of hospital-acquired infections. The incidence of C. diff is steadily increasing and is associated with significant mortality.

The Gut Microbiome Lab at Mayo Clinic is studying how natural variation in individual gut microbiomes relates to clinical risk factors and susceptibility to C. diff infection. The lab's research goal is to develop specific microbial and metabolic biomarkers that can identify people who are at increased risk of infection and would benefit from prophylactic interventions directed toward the gut microbiome.

Dr. Kashyap's lab previously used clinical metadata and patient-derived samples to identify factors associated with susceptibility to C. diff infection. Now the lab is leveraging these patient-derived samples to investigate microbial and host factors that promote an environment conducive for expansion of C. diff and understand the effect of strain level differences in C. diff on the infection's pathogenicity and response to treatment.

The lab is particularly interested in the role of biofilm formation in the persistence and recurrence of C. diff.

Microscopy image of C. diff biofilm from Dr. Kashyap's Gut Microbiome Lab at Mayo Clinic Ex vivo visualization of C. diff biofilm formation

This image shows C. diff (stained in red) overlaid with an image of the polysaccharide matrix (stained in green). The co-localization suggests the presence of a biofilm in this sample.

Dr. Kashyap's research team uses a wide range of techniques and approaches, including scanning-electron microscopy, live cell imaging and metabolomics, as well as novel in vitro and ex vivo assays, including microfluidic devices and organoids. Also, germ-free mice colonized with patient-derived microbiota continue to allow for sensitive in vivo modeling.

The lab's diverse approaches in this project will help develop precision microbiota-based therapies as preventive strategies targeting people who are at risk of C. diff infection.