Change your microbiome, Change yourself

June 7, 2017


Single-celled bacteria living in and on our bodies outnumber human cells by at least 3 to 1 — and perhaps as much as 10 to 1. The latest estimates from the American Academy of Microbiology put our bodies at 37 trillion human cells and our microbiomes — as those bugs are collectively called — at 100 trillion. Yes, that’s right, our skin and guts, mouths and noses, along with every other body surface, are home to 100,000,000,000,000 microscopic bugs. The typical human microbiome is said to represent about 1,000 different species, with wide variation from one person to the next in exactly which species. If it’s still hard to fathom just how big a single microbiome is, consider this: That same report says those microbes, each vanishingly small and seemingly weightless on its own, add up to something like 2.5 pounds.from Genome Magazine see article here


If these statistics have you reaching for the hand sanitizer, slow down. The vast majority of these bugs are no threat at all. Quite the opposite, in fact. Many of them are our best friends and allies in myriad surprising ways that scientists are only now beginning to sort out. And to think that with all of those antibiotics and disinfectants we’ve been waging an all-out war. We really haven’t known microbes (or ourselves, for that matter) at all.


“We’ve had this perception of microbes as germs, as pathogens, as disease-bearing organisms,” says Lita Proctor, a scientist at the National Human Genome Research Institute and program director of the Human Microbiome Project. “Much of the scientific literature for decades and decades has been completely focused on pathogens, and that has also framed our point of view about microbes. But it has become clear that the vast majority of microbes we come in contact with on a daily basis are not pathogenic. They are either benign and couldn’t care less that there is a human nearby or they actually provide a benefit.”


Bacteria play essential roles in the development of our immune systems as newborn babies are colonized at birth and subsequently by microbes from mom and the environment. Once established, those microbes, and particularly those that fit our cells like a lock and key, provide us with energy sources and vitamins humans can’t make on their own. They produce ingredients that act as anti-inflammatories and send signals to our brain. “Good” microbes help us fend off the “bad” ones. We really can’t live without them.


The Other Human Genome


“Instead of declaring war, we need to think in the context of ecosystems that make up our bodies. Figuring out how to encourage good microbes while eliminating the bad will be of increasing importance.”


Despite their importance and value, all of these microbes had gone mostly unrecognized, especially in the biomedical field. That began to change substantially in 2007 when the National Institutes of Health launched the Human Microbiome Project, an effort to catalog the microorganisms living in and on healthy human bodies. It was in some ways a follow-up to the Human Genome Project. Scientists would apply rapidly improving DNA sequencing technologies to define what some like to consider the “other human genome” — the human microbiome — via samples taken from hundreds of healthy people and many parts of their bodies: behind the ear, the inner elbow, the lower intestine, and the mouth. The object of study was literally right under our noses, but it was still so foreign that NIH Director Francis Collins has likened the researchers who carried out the work to “15th-century explorers describing the outline of a new continent.”


The result is the first comprehensive picture of what a normal human microbiome looks like, at least in these modern times. “We have defined the boundaries of normal microbial variation in humans,” said James Anderson, director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives, in the release issued by the NIH as the first big batch of Human Microbiome Project studies were published last year. “Now we have a very good idea of what is normal for a healthy Western population and are beginning to learn how changes in the microbiome correlate with physiology and disease.”


A Veritable Explosion


Since then, there has been an avalanche of new studies connecting the microbiome to health on the one hand and disease on the other. A disrupted microbiome, driven perhaps by the overuse of antibiotics combined with an overprocessed food supply, is now a suspected contributor to the obesity epidemic. Those disruptions often arise from the very first days of life as babies delivered by C-section miss their first inoculation with healthy bacteria found in their mothers’ vaginas. Formula-fed babies also show significant differences in their microbiomes compared to those who are breastfed.

Changes in the microbiome have been linked to obesity, inflammatory bowel diseases, allergies, and asthma, which means the key to treating such disorders could be right under our noses.


A study reported in Science found that differences in the microbiome might help to explain instances in which one individual in a pair of twins is obese while the other is not. Microbiome samples taken from obese twins and delivered to mice led the animals to gain weight in a way that the microbiomes of their leaner siblings simply did not. And a comparable study of mice and twins from Malawi showed that differences in the microbial composition of the gut could explain how two children in the same family sometimes differ so markedly when it comes to malnutrition, too.


If changes to our microbiomes might be a cause of obesity, perhaps they can be a cure for it, too. The gut microbiome apparently undergoes drastic change after gastric bypass surgery, and it gets better: Overweight mice given a “post-surgery” microbiome (but no surgery) lose weight, too.


There are other observations that may seem even less obvious. Changes in the intestinal bacteria may explain why HIV patients — even those who do well with treatment — sometimes still suffer from chronic and ultimately life-threatening diseases. Less diverse gut microbiomes have been linked to the risk of some cancers. Signals produced by the gut microbiome influence blood pressure. The microbiome plays a role in the way our bodies metabolize and respond to some prescription drugs.

In December, a study in mice added to evidence that the microbiome can influence the brain. Animals susceptible to autism-like symptoms as a result of infections suffered by their mothers during pregnancy also showed changes in their microbiomes. When researchers at the California Institute of Technology treated the mice with healthy gut bacteria, some of the animals’ abnormal behaviors and anxiety went away.


Even our family dogs are in on it. Another study just found that the dust in dog-friendly homes protects against allergies and asthma through changes (you guessed it) in the gut microbiome. Young mice fed on doggy dust didn’t react much to cockroach allergen compared with animals fed pet-free dust or none at all. While much of the attention is on the gut, similar things are happening on our skin.


The Modern Age


There is reason to think that the Western microbiome has changed in the last century and not necessarily for the better. A study led by researchers at the University of Oklahoma of microbiome samples taken from ancient people — including Otzi the Iceman and a soldier frozen for decades on a glacier — show that our guts used to look more like those of other primates and rural people in less developed countries. These relatively recent microbiome changes might help to explain the rise in certain kinds of diseases even as modern medicine has enabled us to overcome so many others.


“If you look at a lot of the disease issues of the 20th and 21st century, a lot of them have to do with nutrition and autoimmune processes,” says David Suskind, a pediatrician and gastroenterologist at Seattle Children’s Hospital. “We don’t have a definitive cause yet, but as we look at the new science being done, we see a lot of connections to the microbiome and dysbiosis,” meaning microbial imbalances.


Suskind rattles off a list including arthritis, gum disease, obesity, and cardiovascular disease. His primary interest, though, is inflammatory bowel diseases (IBD) — Crohn’s disease and ulcerative colitis — and their symptoms, including persistent and painful diarrhea. IBD has been considered an autoimmune disease and treated as such with immunosuppressant drugs. But there are reasons to suspect there’s more to it than that.


“IBD is considered an autoimmune process attacking the gastrointestinal tract and other organs,” Suskind says. “But humans have been around for millennia, and IBD is a relatively new disorder.”

Doctors started to notice IBD symptoms about 40 to 50 years ago, he says. Since then, the incidence has only risen. There is evidence to connect IBD to immunity-related genes, but what’s the trigger? Suskind says the evidence is pointing to the microbiome. What would happen if, instead of crippling their immune systems, you gave patients with IBD a new and improved set of bugs?


Powerful Poop


It turns out there is a relatively simple if slightly unappetizing way to do that. The method is called a fecal transplant, and it’s exactly what it sounds like. Doctors infuse patients with slurries of fecal matter taken from healthy people, delivered either to the intestine by enema or the stomach t