Inside You

CLAIRE FRASER, U. MARYLAND SCHOOL OF MEDICINE: I have absolutely come to believe that we cannot understand human health and disease by only looking at the genes in the human genome. We have to take a much more holistic view.

JACK GILBERT, U. Chicago: So we are understanding a new world of microbiology, whereby the bacteria in our environment are living in ecological harmony with us, and we need to embrace that.

ROB KNIGHT, U. CALIFORNIA, SAN DIEGO: It's almost like the Copernican revolution, where instead of seeing ourselves as a center of the universe we start to see ourselves as just one part of the larger picture.

[TITLE: FROM GERM THEORY TO THE MICROBIOME: A NEW VIEW OF OUR HEALTH]

MARTIN BLASER, NYU SCHOOL OF MEDICINE: We've known for centuries now that the human bodies are full of microbes. It began with van Leeuwenhoek in the 17th century, who was looking through the microscope at the little "animalcules" in his mouth.

JUSTIN SONNENBURG, STANFORD UNIVERSITY SCHOOL OF MEDICINE: Fast-forward 200 years and scientists started to realize that microbes actually caused disease.

GILBERT: And when we figured out that these invisible microorganisms were causing disease, it shaped our entire perspective.

GILBERT: We started to sterilize every surface we could. There's only now that we live in such a safe and healthy environment that we realized that actually we may have gone too far. As a species human beings have grown up in a sea of microorganisms constantly interacting with the environment and now that sea of microbes has been cut off from us our immune system is responding in strange ways.

KNIGHT: there's a whole suite of Western diseases that are prevalent in developed countries. These include things like colon cancer, diabetes, obesity inflammatory bowel disease.

SONNENBURG: All of these diseases are explained by a overactive immune system by inflammation, and there's a lot of evidence suggesting that our deteriorated microbiota is actually connected to this misregulation of the immune system.

FRASER: There is a consistent change in the microbiome and that is represented by an overall loss of diversity in the number of species.

LITA PROCTOR, NATIONAL INSTITUTES OF HEALTH: And so it raises germ theory from a single microbe to now an entire community of microbes potentially being the pathogenic agent for causing these disorders and diseases.

GLORIA DOMINGUEZ-BELLO, NYU SCHOOL OF MEDICINE: Not everybody lives the same way. What we have found is that traditional peoples have substantially higher diversity in their microbes compared to us. Our ancestors, and traditional societies still, chew the food for the baby when the baby starts on solids because they cannot blend the food. We have kitchens with blenders, we don't even share the spoons with our kids, we don't sleep with our kids anymore.

BLASER: The early days weeks and months of life are actually important. That's when the microbiome forms, and that's when the microbiome interacts with ourselves. And our hypothesis is that that's been interrupted in recent years, because of such things as cesarean sections, and antibiotics, and excessive washing, and other antibacterial activity.

FRASER: When antibiotics are needed, and that is when someone has developed a bacterial infection, they are absolutely essential. They also kill a lot of the good commensal members of our microbiome.

SONNENBURG: And when you take antibiotics, the microbiota will gradually recover but it never quite recovers to its initial state. And when you use antibiotics more and more the damage becomes more and more severe.

DOMINGUEZ-BELLOW: We will have to optimize and use antibiotics, c-sections with caution

SONNENBURG: Helicobacter pylori is a perfect example of how complex our relationship is with different microbes. H. pylori is traditionally viewed as a pathogen and the causative agent of ulcers can cause gastric cancer in some people.

BLASER: But we began to do studies looking at other diseases, and we found something the opposite. Now a big body of literature has come up that Helicobacter actually has been beneficial effects. Certain organisms are not just pathogenic but the same organism could also be protective--but it depends on context.

W. IAN LIPKIN, COLUMBIA UNIVERSITY: One of the things that physicians and scientists are trying to emphasize now is that we need to back off on the use of antibiotics. We've seen an enormous growth in antibiotic resistance in hospitals and clinics that are life-threatening.

KNIGHT: C.diff is short for Clostridium difficile which is really a kind of bacteria that's like a weed that grows in your gut and what makes it so problematic is that it's resistant to most antibiotics, and it comes with a very nasty kind of diarrhea where you might be going to the bathroom several dozen times a day, and that's coupled with a complete change in the microbial ecosystem of the gut.

SONNENBERG: But what turns out to work well for getting rid of C. diff is actually treating somebody that's suffering with C. diff with healthy stool, actually giving them a fecal microbiota transplant.

KNIGHT: Where essentially what you're doing is you're taking a diverse community from someone who's healthy and then trying to transplant that into the gut.

PROCTOR: But it's such an unusual set of circumstances that it's... that that treatment does not translate for other conditions.

LIPKIN: It's still early days in microbiome research but there's the hope that we may be able to have an impact on a wide range of diseases.

KNIGHT: The potential to improve human health in ways that we couldn't have imagined even a decade ago is tremendous, especially figuring out how microbes change how we metabolize food, how we metabolize drugs, even perhaps how we think, is just amazing.

SONNENBURG: We actually have control over this microbiota through the decisions we make. The most important piece of advice in this regard is just to eat real food. Avoid packaged food, eat a lot of vegetables, a lot of plants legumes, nuts, whole grains, all of these things are great for feeding the microbiota.

FRASER: In a way we've come full-circle, and we're back looking at some of the same microbial communities that van Leeuwenhoek looked at with his microscope 350 years ago.

BLASER: The microbes in my body by and large are good they're good for me, and that's the paradigm switch, and we have to learn how to work with our good microbes to help us fight the bad ones.