Microbiomes: Tiny Organisms with a Big Impact

Donald L. Trump, MD, is board certified in internal medicine and medical oncology. Dr. Trump is the CEO and executive director of the Inova Dwight and Martha Schar Cancer Institute. He is the former CEO and president of an NCI-designated comprehensive cancer center, Roswell Park Cancer Institute. Dr. Trump maintains an active clinical and translational research program in vitamin D therapy, primarily focused on patients with cancers of the genitourinary system (prostate, bladder, kidney and testis). He has led numerous investigator-initiated and cooperative group trials evaluating new treatment approaches to genitourinary cancers. Read Dr. Trump’s profile.

I thought it was complicated when I tried to learn what it meant to sequence a person’s whole genome!

I have been following the continuing development of the study of microbial populations living in and on the human body and the diseases to which we are prone. This field of microbiome research is fascinating.

What is a Microbe?

A microbe is a microscopic organism, a germ, a living thing too small to be seen with the naked eye. Microbes include many diverse life forms, including bacteria, viruses and fungi. We are full of microbes: They live on our skin, in our digestive tract, in our airways … almost everywhere in and on the human body.

A microbiome is the full collection of all the microbes in a region of the body. Microbiomes are incredibly important to our everyday health—they act as our body’s “bouncer.” Substances that want to enter our body (food, drugs, chemicals) must first past through a layer of microbiomes. The microbes may even prevent certain chemicals from ever entering our cells. Changes to our microbiome mean changes to our health.

When Viruses and DNA Meet

Research has shown that viruses, such as the human papillomavirus (HPV), integrate with the DNA, becoming part of the genome. There are breaks in the DNA, and the HPV virus is able to integrate itself into the DNA strand. This integration increases the likelihood that cancer will develop. We have seen this genome integration with hepatitis B and Epstein-Barr virus (EBV) as well.

Therefore, perhaps it should not surprise us that other “infestations” may wreak havoc on our health. Helicobacter pylori is a type of bacteria that may live in our digestive tract. Occurrence of H. pylori in the stomach is one of the first bacterial infections shown to contribute to the development of stomach cancer.

Cancer-Causing Bacteria?

But how does that happen? Perhaps we can understand that when viruses such as HPV, HBV or EBV integrate into a person’s genome at just the wrong place, it can result in a cancer-causing event. But how does a bacterial infection cause cancer? Two theories are:

• Through chronic inflammation and cytokine effects on connective tissue and inflammatory cells
• Through free radical production as a byproduct of chronic infection with DNA damage

Our bodies are full of microbes—they reside in our gastrointestinal tract, oral cavity, vagina and bronchial airways. We are now beginning to see that this microbial content can lead to disease.

Gene-Environment Interaction

One report suggests that sulfate-reducing bacteria in the colon can lead to the production of arsenic thiol compounds. These arsenics can be much more genotoxic, meaning they damage DNA within the cell, leading to mutations that can cause cancer.

Now there is a gene-environment interaction of interest! We are also learning that organs and areas of the body we once thought were completely free of germs (sterile) may harbor organisms. We are just beginning to learn how these previously unknown microbiomes may contribute to disease—or to health. The study of these microbiomes may help us gain insight into many cancers whose cause we do not yet understand.

And maybe microbiomes/organisms help explain why some of the drugs we have come to rely on do not work in some patients?

Pharmacogenomics: Part of the Answer

Pharmacogenomics is the study of variations in how individuals metabolize drugs. But new research suggests that the bacterium Eggerthella, an intestinal inhabitant, can inactivate digoxin, a drug to treat congestive heart failure and modify digoxin pharmacokinetics.

So it isn’t just my liver function, enzyme content and kidneys that determine how I handle a drug. In at least some instances, the germs in my body change how my body handles a drug. And it is becoming more and more complicated.

When Microbiomes Change

Changes in the microbiome of humans appear to change the risk of asthma, hypertension, inflammatory bowel disease, type 1 diabetes and even obesity. And many things we do or take can change our microbiomes.

One study showed that short courses of different antibiotics can change the microbiome of mouse pups. These changes are associated with measureable differences in weight and bone growth later in life. These and other studies of the increasingly exciting science of the study of the bugs that live in and on us are summarized in this article.

Microbiomes are an exciting, and certainly complex, field of medicine. Studies of our microbial content will give us a deeper understanding of many of the diseases which have puzzled us for decades, and in some cases, have become more prevalent in recent years.