Microbiome Program
The invention of the microscope long ago allowed scientists to understand how microscopic organisms can cause and transmit infections in humans. Now, using genomic sequencing, researchers are discovering that communities of archaea, bacteria, fungi and viruses inside and on every person's body, known collectively as the human microbiome, do much more for people than we ever imagined.
Human microbiome communities and their genetic material far outnumber human cells and genes, and this population plays an important role in maintaining health. When it is disrupted, it can lead to serious health problems.
For example, consider what can happen when people are exposed to antibiotics. In some people, antibiotics can cause an imbalance of the normal bacterial communities and lead to overgrowth of Clostridium difficile and severe inflammation in the bowel. Reestablishing the normal microbiome through direct microbiome transplant can restore health.
In the Microbiome Program, researchers are studying many more questions about the relationship between the microbiome and health and disease, including:
- What can the microbiome reveal about health?
- Can microbial communities in the colon be the cause for irritable bowel symptoms?
- How do gut microbes affect other parts of the body, such as the joints, liver and immune system?
- Can gut microbial metabolites be the reason that diet influences colon cancer development?
- Can genomic sequencing techniques help researchers identify organisms that cause vaginosis and reproductive health problems?
- Can an imbalance in the microbiome lead to autoimmune diseases?
- How do scientists and clinicians translate their insights about the microbiome into new diagnostic and prognostic approaches?
Projects
C. albicans is a type of fungus that is commonly found within the human microbiome. It is known for causing infections such as thrush, diaper rash and potentially even systemic disease.
C. albicans also can interact with other microbes within the microbiome, either positively or negatively. For example, interactions with beneficial bacteria can help inhibit the growth of C. albicans, while interactions with other pathogenic bacteria can promote its growth and increase the risk of infection. In addition, C. albicans can produce substances — such as metabolites or toxins — that can alter the microbiome's environment, which can further influence the interactions between the fungus and the microbiome that may affect immune response and development.
This project seeks to understand the role of C. albicans in diseases and conditions such as asthma, atopic dermatitis, food allergies, intestinal dysbiosis and immune response.
Altered composition of the intestinal microflora has been linked to disorders of the gastrointestinal tract, including gluten sensitivity and the risk of irritable bowel syndrome-like (IBS) symptoms.
This study is characterizing the intestinal microflora of patients with celiac disease and a subset of patients with IBS to identify and develop novel therapies, as well as preventive interventions for individuals with a high risk of developing gluten sensitivity and IBS-like symptoms.
C. difficile infection is the leading cause of nosocomial diarrhea in the U.S. Despite advances in treatment, C. difficile infection continues to be associated with poor outcomes, with some patients requiring urgent surgery for life-threatening infections and others experiencing relapses and chronic disabling symptoms.
This project is characterizing the fecal microbial composition in the colon to develop tools that can predict response to treatment and the risk of relapse.
Sustained alterations of a normal gut microbiome, coupled with a compromised intestinal mucosal barrier, can have an extended effect on systemic immune response. This can be a precursor to chronic inflammatory and autoimmune disorders, such as rheumatoid arthritis.
Characterizing the composition of the intestinal microflora of patients with rheumatoid arthritis and their healthy family members could define specific microbial species or ecological properties, such as biodiversity, that may be responsible for microbial imbalances (dysbiosis) in patients.
This will help in improving predictive and diagnostic protocols for individuals at high risk of developing rheumatoid arthritis and may lead to novel treatment strategies.
Dietary factors are known to influence the risk of colon cancer development, but the exact way dietary factors cause cellular and DNA damage has not been determined. Without information on these underlying mechanisms, only empiric approaches to correcting dietary affects are available, and unfortunately such preventive strategies have been unsuccessful.
This project assumes that people's diets and resulting intestinal microbiome communities create metabolites that can harm bowel cells and produce DNA damage, leading to cancer development. Researchers are testing two metabolic pathways with toxic potential, including sulfate-reducing bacteria and methanogens.
Bacterial vaginosis is a condition that can have important implications for reproductive health at many levels. Mounting evidence suggests it may be a result of critical changes in the local microbiome.
In this study, researchers are using modern genomic sequencing techniques to assess the role of microbial communities and individual microbial contributions to the disease, with plans to develop both novel diagnostic and therapeutic approaches from this new information.
Early disease diagnosis and time-longitudinal therapeutic monitoring can lead to timely adjustment of interventional strategies for each patient. This project focuses on the development of a point-of-care device for the rapid detection of bacterial infectious diseases to prompt timely treatment, as well as a portable microfluidic platform to monitor immune-mediated response from therapies.
The goal is to deploy these platforms in intensive care units, operating rooms and homes to assist medical professionals with decision-making in individualized medicine.
This project focuses on the development and validation of a suite of causal inference, artificial intelligence and machine learning tools for enhanced risk prediction using multiomic data. Risk prediction tools for targeted identification of the specific genotypes and phenotypes of future malignancies will augment individualized clinical management in the prevention and treatment of cancer.
These multiomic risk prediction algorithms will provide personalized cancer risk estimates for guiding clinical decision-making based on genetic, epigenetic, microbiome, proteomic, metabolomic and transcriptomic data risk factors.
Program leaders
Individualized Medicine — Dianne's Story
Microbiome transplant clears a patient's antibiotic-resistant intestinal infection.
Microbiome Animation
Microbiome research explores the genetic code of the body's microorganisms, using the latest techniques to profile an individual's microbiome to detect, prevent and diagnose infections and other diseases.