The invention of the microscope long ago allowed us to understand how bacteria can cause and transmit infections in people. Now, using genomic sequencing, we are discovering that communities of bacteria, known as the human microbiome, do much more for us than we ever imagined.
The number of human bacteria and their genetic material far outnumber human cells and genes, and we know that bacteria play an important role in maintaining health. When this population of bacteria 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. Re-establishing the normal microbiome through direct microbiome transplant can restore health.
In the Microbiome Program, many more questions about the relationship between the microbiome and health and disease are being investigated:
- Can microbial communities in the colon be the cause for gluten sensitivity and irritable bowel symptoms?
- How do the colon organisms affect other parts of the body, such as the joints?
- Can colon microbial metabolites be the reason that diet influences colon cancer development?
- Can genomic sequencing techniques help us identify organisms that cause vaginosis and reproductive health problems?
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.
Clostridium Difficile Infection
Clostridium difficile infection is the leading cause of nosocomial diarrhea in the U.S. Despite advances in treatment, Clostridium 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.
Alterations of a normal gut microbiome can affect mucosal immunity by modulating the integrity of the intestinal mucosal barrier and have an extended effect on systemic immune response.
Characterizing the composition of the intestinal microflora of rheumatoid arthritis patients and their healthy family members could potentially 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 manner in which dietary factors cause cellular and DNA damage has not been determined. Without information on these underlying mechanisms, we only have empiric approaches to correcting dietary affects, and unfortunately such preventive strategies have been unsuccessful.
This project makes the assumption that the diet and resulting intestinal microbiome communities create metabolites that can harm bowel cells and produce DNA damage, leading to cancer development. Two metabolic pathways with toxic potential are being tested, 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.
This study is 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.
Heidi Nelson, M.D.