Infectious Diseases

Jessica Allegretti

Jessica Allegretti, M.D., M.P.H.

Medical Need

The incidence of C. difficile infection (CDI) has risen markedly over the last decade, with recurrence rates as high as 20-30%. Undefined elements of the healthy intestinal microbiome protect against the development of CDI. Bile salts may function as a critical regulatory pathway that either stimulates (primary bile salts) or inhibits (secondary bile salts) the growth of C. difficile. We have demonstrated that secondary bile acids were significantly elevated in the stool of controls compared to both first time CDI (fCDI) patients and recurrent CDI (rCDI) patients and primary bile acids were significantly elevated in the stool of rCDI patients compared to controls. These may serve as novel biomarkers.

Current Research
  1. We are validating the use of bile salt profiles as a predictive tool to identify CDI recurrence in patients experiencing their first episode of CDI.
  2. We aim to understand the crucial interplay between organisms that contain bile salt hydrolase genes and bile salt profiles in the pathophysiology of recurrent CDI, and utilize this information to develop biomarkers of recurrence in order both to identify patients at risk earlier in their course and ultimately treat these patients more effectively.
Publications
Lynn Bry

Lynn Bry, M.D., Ph.D.

Medical Need

The microbiota represents the diverse microbial ecosystems that live on and in us. Microbes colonize our skin, gut ,and other exposed surfaces. They provide critical functions in our development and maturation through their production of essential vitamins, maturation of our immune system, and life-long interactions with our bodies. The microbiota can also contribute to a variety of diseases including inflammatory bowel disease, susceptibility to infections and development of allergic and auto-immune diseases.

Current Research
  1. Clostridium difficile infection is the most common cause of hospital-associated infections in the US. We are defining precision biomarkers to rapidly identify patients at risk for recurrent infection of C. difficile, and therapeutic microbiota to provide a toolkit of defined organisms to treat based on microbial activities needed by the individual patient. Our efforts are developing (1) diagnostic markers for C. difficile recurrence, (2) robust computational algorithms to predict which patients are likely to recur, based on clinical, microbiome and microbial metabolite data, and (3) efficacy of consortia of human commensal bacteria in the treatment of different patient strains of C. difficile.
  2. Immunomodulation: My group also studies and has developed defined microbiota to promote immunomodulation of the mucosal immune system. In particular, we are taking defined consortia of human commensals into clinical trials to test their efficacy in food allergy by using gut lumenal microbes to alter allergic T cell responses against ingested foods. We believe the use of therapeutic microbiota in this manner has potential broad applicability to other diseases including IBD, cancer and other forms of auto-immune diseases.
  3. Prospective Genomic Surveillance Program: My group oversees a multi-institutional program that genome sequences highly drug resistant strains of bacteria cultured from our patients to identify the underlying causes of resistance, their carriage by specific bacterial strains, and capacity for transmission by vectors including plasmids and transposons. We work with local infection control teams and clinical microbiology labs to leverage this information in directing surveillance activities and clinical actions to further prevent spread.
Publications
Georg Gerber

Georg K. Gerber, M.D., Ph.D., M.P.H.

Medical Need

Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes inflammatory arthritis. Patients with RA have excess cardiovascular and respiratory morbidities and have excess mortality compared to the general population. Our group is using precision medicine to understand the etiology, optimize treatment, and decrease the morbidity burden for patients with RA using clinical trials, observational cohort research studies, and harnessing the wealth of data in electronic medical records.

Current Research
  1. New computational approaches for analyzing dynamics of complex host microbial ecosystem.
  2. New synthetic biology systems and computational approaches for studying microbiome functions in vivo.
  3. Elucidating the role of the microbiome in infectious and autoimmune diseases:
  4. Colonization resistance to pathogens conferred by the gut microbiota.

    1. Role of the gut microbiota in food allergy in pediatric populations.
    2. Role of the microbiota in multiple sclerosis.
Publications