We’re mostly microbes, so let’s treat them with a little respect. Our lives depend upon it. A Q&A with Cornell immunotoxicologist Rodney Dietert.
When we think about what makes each of us unique, we naturally think about genes. And why not. Genes determine single traits, like hair color, and predispose us to conditions, both good and bad.
But our human chromosomal DNA, which encodes for around 22,000 genes, is really only a small part of who we are. Among humans we also carry around 10 million microbial genes—mostly bacterial, but also viral, fungal and parasitical—that comprise what is known collectively as the microbiome and which drive the behavior of those trillions of microbes that live on or in us.
It is this microbial community that Rodney Dietert, a professor of immunotoxicology at Cornell University, suggests could be the real nerve center driving human health, as important to our human evolution as the genes that we inherit from our parents.
Dietert is not alone in his fascination with the microbiome. In the mere 15 years since Nobel Laureate Joshua Lederberg coined the term, the microbiome has sparked an incredible amount of research. Along with the obvious connection to gastro-intestinal disorders, where most of our bacteria reside, our microbiomes are also thought to influence conditions as varied as depression and anxiety, autism, diabetes and obesity, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, fibromyalgia, and perhaps some cancers. The pharmaceutical industry has also taken a keen interest in the microbiome. And the US government recently launched a US$121 million National Microbiome Initiative to compare microbiomes across different ecosystems.
But Dietert takes the microbiome to a much broader level in his fascinating new book, “The Human Superorganism: How the Microbiome is Revolutionizing the Pursuit of a Healthy Life.” Dietert, who has a PhD in immunogenetics and has spent much of his career studying the impact of immunotoxicity on chronic diseases, says a “full set of microbial partners” is required from birth to stay in balance. Not surprisingly, given our life styles, society hasn’t done a good job nurturing the relationship. Put another way, by inadvertently depleting, translocating, overproducing or killing off many of the species populating our microbiota, we have triggered immune-based dysfunction that is in a constant state of inflammation. These unfavorable conditions have ultimately paved the way to an epidemic of chronic diseases.
As alarming as this sounds, Dietert is not in the business of spreading dystopian visions of the future. He’s also not intent on playing the blame game. Many of the modern-day inventions that have been altering our microbiome—antibiotics, Cesarean sections, frozen and processed foods, rapid urbanization, misdirected efforts at human safety testing,—began with the best of intentions, he notes. Rather than rail against past practices, Dietert wants to educate the public about the options we have to rebuild our individual microbiomes collective microbiome.
Dietert, part of the award-winning documentary film, “Microbirth” and an occasional guest blogger for Eureka spoke with Senior Scientific Writer Regina McEnery about the state of our microbiome. Here are his edited responses.
Is microbiome science still an emerging one?
RD: If you were to talk to bacteriologists from the 1960s, I think they would say it’s always been there, but it never registered that it was doing the kinds of things we now know it does. It also never registered that it really is an integral part of us and which I contend we need to stay healthy.
When did you first become interested in the microbiome?
RD: Most of my work has been spent looking at ways of protecting and optimizing the immune system. My interest in the microbiome came about when I was trying to prepare a challenging scientific paper about the most important measurement in a baby that would predict a life filled with health. I thought that it had to be an immune answer, but I was road-blocked, I couldn’t come up with a satisfying response. So I went to bed, and woke up from a dream with the idea that we’re not supposed to be a pure species, that in order to be healthy we have to be thousands of species, and that the sooner we self-complete as a superorganism the better our chances are for a healthy life.
So it seems that one of the central messages of your book is that the microbiome is really a bigger player than the genome in determining human health.
RD: I’m not saying human chromosomal genes are unimportant. They are involved in hair color and a whole variety of things that we can see. Unfortunately, it is what we don’t see where the microbiome is really the dominant force. Our microbiome consists of just under 10 million genes, which make a variety of enzymes and signaling molecules. Our microbial cells are sitting in all the portals of entry—on the skin, in the airways, in the gut, in the urogenital tract. Everywhere we engage our external environment it’s operating first, before our mammalian cells. One place to look to see this impact is the lab of Curtis Klaassen, an internationally-known liver toxicologist from the University of Washington. He wrote a series of reviews over the last 12 months that focused not only on the microbiome’s capacity to engage in metabolism of food, environmental chemicals and drugs, but its control of liver metabolism, which it did so rather heavy-handedly.
Cesarean sections adversely affect the microbiome, but breast milk enhances? How so?
RD: Studies have found that babies born vaginally have a microbiome that looks like the mother’s. Children born by cesarean section acquire bacteria from other sources besides the mother—health care workers, surfaces. Since the bacteria aren’t diverse enough adequate colonization of the lower gut is delayed. Antibiotics given to mothers to prevent postsurgical infections can also harm the maternal microbiome that needs to be passed on to the infant, and impairs bacterial signals the baby is receiving from maternal microbes just prior to delivery. Breast milk helps by feeding the baby’s microbiome. In fact, it is one of the primary functions of breast milk.
You actually refer to a damaged microbiome as a birth defect.
RD: If we are missing a significant percentage of the microbial population and diversity that would make us healthy, this increases the risk of NCDs and some infectious diseases. I am arguing it is a birth defect because it is the equivalent of missing something major that is an integral part of your body, and has predictable health outcome as a result. The good news is that it’s treatable.
What other approaches can be adopted to re-boot the microbiome?
RD: One way would be to combine a dietary strategy with rebiosis—probiotics, or if warranted fecal microbiotic transplantation or other methods of installing bacteria not just in the gut, but in the skin and other portals open to rebiosis. Physicians often tell their patients that they should just change their diet, lose weight and they’ll get out of the metabolic syndrome of diabetes and obesity. But the reality is that only a low percentage of individuals are able to do that. And we now realize it’s not the patient’s fault. They are trying. But if you never change the microbes and then suddenly use a blunt instrument of dietary change to try to force a different microbiome within a patient, it’s extremely difficult because those microbes have grown up on pasta and pizza and are calling typically for those energy forces. So if you want a Mediterranean diet, for example, or more leafy vegetables, then put the bacteria in there that calls for it because that is half of the battle.
How is our understanding of the microbiome reshaping drug development?
RD: As toxicologists, we evaluate environmental chemicals and drugs for safety, but in hindsight we should also be screening the microbiome and ensuring its safety because commonly used drugs do impact it. Many of the side effects from drugs are related to damage of the microbiome. You should also be able to make the drugs more effective by assessing an individual’s microbiome and tailoring drug therapy with microbiome adjustments.
What will the areas of microbiome research and application look like in 10 years?
RD: More fully-vetted, microbiome-based products and rebioisis strategies will be available not just for the gut but also for other body sites (e.g., skin, airways, urogenital tract). An emphasis is likely to shift from microbial species counting to gene composition both among our microbes and new probiotics products. It is a gene’s presence and the signaling and metabolic ramifications of that microbial gene’s product that affects our physiology and development. More will be known about how microbial species network both among themselves and with us over the next decade. I think that physicians will have new microbiome profiling and therapeutic tools at their disposal. Microbiome profiling will become a routine part of our medical records. This will be an important part of future precision medicine and the war against ongoing the noncommunicable disease epidemic. More knowledge will be available about the “normal aging” of a healthy microbiome so that we better understand how to manage a healthy microbiome at each decade of a person’s life. Finally, the next generation of drugs will be designed to work with and through the microbiome.
How to Cite:
Dietert, Rodney. The Microbial Shuffle. Eureka blog. Jul. 27, 2016. Available: http://eureka.criver.com/the-microbial-shuffle/