Breakthrough technologies such as gene sequencing have revealed the vast complexity of microbial life in and on the human body. A growing number of researchers at Fred Hutch are investigating how the microbiome may be tied not only to cancer but also to obesity, heart disease, mental health, vaccine efficacy and responses to cancer treatments such as chemotherapy. This work has important implications for prevention and for developing new therapies that harness immune defenses to fight cancer and disease.
Diet, Microbes and the Immune System
Among the longest-running microbiome research projects at Fred Hutch are dietary studies that look at chemicals that are released when different communities of microbes break down foods in the gut. Some of these reactions can turn foods into carcinogens. Others metabolize byproducts that are thought to have anti-cancer and anti-inflammatory properties.
Dr. Johanna Lampe leads the Flax FX study, which looks at the role of the microbiome in developing and maintaining a healthy immune system — specifically, by studying whether consumption of flaxseed could help prevent colon cancer. Flaxseed contains compounds called lignans that can be converted by gut bacteria into biologically active compounds that have been shown to be protective against colon cancer in mouse studies. Dr. Meredith Hullar is another researcher who studies the gut microbiome and its complex interplay with diet and cancer risk. She and Lampe are involved in the Multi-Ethnic Cohort study, which compares the microbiome profiles of 6,000 men and women from five different ethnic groups in Hawaii and California. The study aims to identify possible links between the makeup and function of the gut microbiome and risks of obesity and cancer, as well as to explore the connection between gut bugs, the brain and behavior.
Gut Microbes and Gastrointestinal Disease
Disruptions to the balance of microbial species in the gut have been associated with several gastrointestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, nonalcoholic fatty liver disease and bowel cancers.
Dr. Nina Salama has been exploring the human microbiome for more than 15 years, focusing on Helicobacter pylori, or H. pylori, a bug that thrives in the acidic environment of the stomach and is implicated in stomach cancer. Although half of the world’s population is infected with H. pylori, only a small fraction of those people develop stomach cancer. Salama and her colleagues are investigating whether the cancer-causing mechanics of H. pylori are tied up in complex interactions with other microbes and the enzymes and tissues of their human hosts.
Dr. Neelendu Dey is investigating the role of the gut microbiome in the development of colorectal cancer through its effects on intestinal nerves, whose activity is influenced by bile acids, which are in turn modified by gut bacteria in various ways. Dr. Megan Koch studies the microbes that colonize the gut in babies immediately following birth. Her discoveries include showing that maternal antibodies transmitted to offspring via breast milk are critical for newborn health.
Microbiome Research Initiative
The Microbiome Research Initiative links investigators across all Fred Hutch divisions who share a common interest in microbiome research, capitalizing on recent advances in the field and the deep expertise of our scientists in all aspects of human biology, cancer and infectious diseases. It is led by Dr. David Fredricks, whose groundbreaking work in this area includes some of the first comprehensive studies of microbial populations in the vagina that cause bacterial vaginosis, which is associated with preterm birth, pelvic inflammatory disease and elevated risk of sexually transmitted infections, including HIV.
Effects of the Microbiome on Disease Treatment
Microbial species in the body can have a significant effect on patients’ responses to medical treatments. For example, in stem cell transplant patients, the population of microbial communities in the gut can change dramatically in response to infection or antibiotic treatments. Dr. David Fredricks and his team tracked and characterized these disruptions and showed that when certain bacterial species dominate the microbiome, creating a less diverse community, it significantly increases the risk of a patient developing severe graft-vs.-host disease, a debilitating and potentially deadly complication in which transplanted immune cells attack the patient’s healthy tissues.
Microbes and Vaccine Efficacy
When a once-promising HIV vaccine failed completely in a global trial, that result may have been due to interference from common bacteria in the human gut. Instead of producing new antibodies against HIV, the experimental vaccine awakened old antibodies formed against gut bacteria acquired during early childhood. Dr. James Kublin helped oversee the HIV vaccine trial and is now studying how gut microbes can alter immune responses. This work could lead to a better HIV vaccine as well as show how the immune response to gut bacteria might be tapped to develop more effective vaccines of all kinds.
