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Published On Nov 17, 2014

Basic Research

Where Have All the Microbes Gone?

Internist and researcher Martin Blaser believes that disturbances in the gut may underlie several modern maladies.

Martin Blaser is the director of the Human Microbiome Program at New York University’s Langone Medical Center and a long-time researcher on the effects of microbes on health. His recent book, Missing Microbes, considers why the vast ecosystem of bacteria and other microscopic life is rapidly becoming less diverse—and the dangers that this situation poses.  

 

Q: In Missing Microbes, you present evidence that we are losing many species of bacteria that were once common in our gastrointestinal tracts. Why are they disappearing?

A: The microbes that live in and on the human body aren’t there by accident. They have co-evolved with us. Natural selection has given us certain populations of microbes with specific functions that all humans share—that all mammals share. We have them because they are beneficial to us. They help us with digestion and with making vitamins, and they protect us against invaders and train our immune systems, among many other benefits.

My hypothesis is that we now do things, including using antibiotics, that are inadvertently upsetting our balance of microbes and even leading to the extinction of some organisms. That in turn changes physiology, and alters health. Consider all of the diseases that have been rising in prevalence since World War II, when antibiotics were first used. Either each of these diseases—obesity, allergies, inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, among others—has its own cause, or there’s some common cause fueling all of them. I believe that cause could be a change in our ancient microbiota. 

 

Q: Fecal microbiota transplant (FMT) reintroduces bacteria from a healthy person into the gut of someone who’s sick, and it has proven very successful in treating C. difficile infections. What can we learn from that? 

A: FMT is an attempt to restore a microbial ecology that in C. diff infections is very disturbed. That the treatment is so effective shows that ecological restoration can work dramatically well. Now we can move to the next logical step. Within five to 10 years, science will come up with a mixture of microbes that is much narrower and more clearly defined that can be used instead of actual FMT. That will make it much easier to understand what’s going on with the treatment as well as making it easier to adapt and regulate. 

 

Q: Will FMT’s effectiveness against C. diff translate to other diseases?

A: C. diff has a single cause and is very acute. Other gastrointestinal disorders have much more complex causes, and we’ll just have to see how today’s clinical trials pan out. Inflammatory bowel disease is so clinically variable that it may be hard to find a one-size-fits-all treatment. 

 

Q: You suggest that cesarean sections and early antibiotic use contribute to the depletion of the microbiome. Why is that a problem?

A: Our most recent research supports the idea that there is a developmental window that the microbiome participates in. If you perturb the microbiota during that window—for example, with C-sections, which deprive infants of the bacteria they would normally get from the mother’s vagina, or through early antibiotic use, or both—you can end up with long-term consequences. In a study we published in August in Cell, we treated newborn mice with antibiotics for four weeks. That disturbed their microbiota, and although after we stopped the treatment the mice returned to normal, they later became obese—one problem that may be caused when the microbiota is out of balance. We also saw changes in immunity—specifically, in gene expression in the intestinal wall, affecting inflammation and immunity. 

 

Q: Can you give a specific example of how a missing microbe affects health?

A: Helicobacter pylori, a bacterial species that resides in the stomach, is clearly disappearing. In the stomachs of people who have H. pylori, there are a lot of immune system cells, particularly a specific type of T-cell that helps modulate immunity and may help protect against asthma. Without H. pylori, and without those regulatory T-cells, you may get an immune response that’s hard for the body to shut off. And when we did epidemiologic studies, we found that kids without H. pylori were more likely to have asthma.  Experimental studies in mice by a Swiss group provide direct support for a protective role of H. pylori.

 

Q: Does the evidence of a depleted microbiome mean we shouldn’t use antibiotics at all? 

A: Whether or not someone takes an antibiotic is largely based on what a health practitioner feels is best in a particular situation. But most of the time, when people think they need an antibiotic they’re looking at its benefit, not its cost—and we are learning that there are more and more costs. In Sweden, they use only 40% of the antibiotics we use in the United States. And the people there are just as healthy as we are, even with that much more judicious use. I’m hoping we can get to that point. 

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