Out-of-focus person in background touching overlay with diagram of digestive system in foreground

Microbiomics 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 Microbiomics 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.

Changes in the makeup of the intestinal microflora have been linked to disorders of the gastrointestinal tract, including gluten sensitivity and the risk of symptoms like those of irritable bowel syndrome (IBS).

This study observes and describes the intestinal microflora of patients with celiac disease and a subset of patients with IBS. The goal is to identify and develop new and unique therapies and preventive interventions for individuals with a high risk of developing gluten sensitivity and IBS-like symptoms.

C. difficile infection is the leading cause of hospital-acquired diarrhea in the U.S. Despite advances in treatment, C. difficile infection continues to be associated with poor outcomes. Some patients require urgent surgery for life-threatening infections. Others experience relapses and chronic disabling symptoms.

This project is describing the makeup of the microflora in feces in the colon. The goal is to develop tools that can predict response to treatment and the risk of relapse.

Changes to a normal gut microbiome that go on for an extended period of time, along with a weakened 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.

Researchers are describing the makeup of the intestinal microflora of patients with rheumatoid arthritis and their healthy family members. The research team aims to identify specific microbial species or ecological properties — such as biodiversity — that may be responsible for microbial imbalances in patients.

This research will improve how healthcare professionals predict and diagnose people who are at high risk of developing rheumatoid arthritis. It also may lead to new and unique treatment strategies.

Scientists know that dietary factors influence people's risk of developing colon cancer. But they have not figured out the exact ways that dietary factors damage cells and DNA. Without this underlying information, healthcare professionals can only observe and experiment to correct patients' dietary effects. So far, such preventive strategies have mostly 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. This damage can lead to cancer. 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. Growing evidence suggests it may be a result of changes in the microbiome of the vagina.

In this study, researchers are using genomic sequencing to evaluate the roles of microbial communities and individual microbes in this disease. The research team plans to use this information to develop new and unique ways to diagnose and treat bacterial vaginosis.

Diagnosing diseases early and monitoring treatments across time can help healthcare professionals adjust interventional strategies for each patient at the right time. This project focuses on developing a device that healthcare professionals can use at the time and place they see patients — the point of care. The device will be used to quickly detect bacterial infectious diseases to help patients get timely treatment. Researchers also are developing a portable microfluidic platform to monitor how patients' immune systems respond to treatments.

The goal is to deploy these platforms in intensive care units, operating rooms and homes to help medical professionals make decisions about individualized care.

Researchers are developing and testing a group of causal inference, artificial intelligence and machine learning tools that will use multi-omic data to better predict patients' risk of getting cancer. These tools will identify the specific genotypes and phenotypes of future cancers. They will help healthcare professionals use individualized medicine to prevent and treat cancer.

These risk prediction algorithms will provide personalized cancer risk estimates for guiding clinical decision-making based on multi-omic risk factors.

 

Individualized Medicine — Dianne's Story

Microbiome transplant clears a patient's antibiotic-resistant intestinal infection.

Microbiomics Animation

Microbiomics 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.