The human genome is made up of about 23,000 genes. That’s a fairly impressive figure. Until you consider this: the number of non-human genes each of us carries around — from the bacteria, viruses and other pathogens living in and on us — totals 8 million.
Most of the cells in the human body aren’t even human. Indeed, bacterial cells outnumber human cells 10 to 1. Which is why the exploration of the human microbiome — the collective population of all the non-human cells and genes that inhabit us — is currently one of the fastest rising fields of medical research.
What scientists are discovering is that these microbes are not just freeloaders or invaders. Rather, they’re crucial facilitators of many of our basic bodily functions: from digesting food and producing vitamins to fending off harmful infection and recovering from illness. They not only keep people healthy, but they may also explain differences in individual health — why people respond differently to the same drug or why some people develop chronic diseases and others don’t.
Now, for the first time, researchers are offering an unprecedented peek into the hidden world of the human microbiome. In a massive effort, a consortium of scientists, both publicly and privately funded, have published 16 papers in the journals Nature and PLoS One. The new research includes full genetic sequences of certain familiar species of microbes that reside in various parts of the body, including the nose, mouth, intestines and vagina, as well as descriptions of bacteria that have never before been seen.
“This is a great vast unknown territory we have never studied before,” says George Weinstock, associate director of the genome institute at Washington University at St. Louis and co-author of five of the papers being published on Wednesday. “There are so many different organisms in so many different places in our body, that they have to have a huge impact on our health. But for all intents and purposes [this world] is unknown. We’ve only scratched the surface of understanding the extent to which these microbes can impact our health and who we are.”
Several papers draw the first links between microbes and common human ailments such as irritable bowel syndrome, unexplained fever in children and even acne. The papers also explore the idea of establishing a “reference” human microbiome — much like the reference human genome — as the standard for what’s “normal” in the body’s microbial population. Comparing the reference microbiome against variations in individuals can help researchers understand how such differences in bacterial makeup may contribute to diseases and chronic conditions, from obesity to asthma, cancer and perhaps even autism.
That is the goal of the Human Microbiome Project, a multiyear, $153 million effort launched in 2007 by the National Institutes of Health to sequence the genes of all the microbes living in and on the human body. Two of the newly published papers came out of the project’s early work, which involves 4,788 microbial specimens from 242 people — including Charles Rathmann of the Institute of Clinical and Translational Sciences at Washington University School of Medicine. “The more we learn about the bugs that naturally occur in our bodies, the sooner we can learn about how to manipulate them and think about creating new treatments to prevent or even cure disease,” Rathmann says.
Volunteers like Rathmann provided bacterial samples from their mouths and noses, from skin scrapings behind the ears and in the crook of the elbow, from the vagina and from stool samples. Researchers found up to a thousand different bacterial strains living on each person — and the makeup of these communities differed from one person to the next. Particularly astounding is the fact that the 8 million unique genes making up the microbiome — including, surprisingly, those from bacteria that are normally associated with disease — could coexist in a complex equilibrium not only with our 23,000 human genes, but also with one another. “When we talk about genetics, we need to factor in the microbial genome as well,” says Lita Proctor, coordinator of the Human Microbiome Project. “The two systems — the human genome and the microbial genome — co-evolved together.”
In fact, it’s hard to imagine how humans would have evolved without the help of our microbial inhabitants. When it comes to the everyday task of keeping the body running, microbes play a critical role: most humans wouldn’t be able to digest the fiber in vegetables without the help of gut bacteria that break it down. Bacteria in the vagina, which sterile newborns encounter during birth, are humans’ first exposure to the outside microbial world, which will eventually train the immune system to distinguish good bacteria from bad. (Babies born by cesarean section acquire different microbiomes.) “This is not just exploratory science, but it’s meant to understand what is this dark matter of microbes in our bodies that we didn’t know anything about, and to shine a light on this world,” says Proctor. “We need to know what is their role, what are they doing for us, and how can we support that role if it helps our health.”
Already, promising research among animals and some human patients has shown that manipulating these bacterial communities can have dramatic effects on individual health. In animal studies, for example, obese mice that received microbial transplants from normal weight mice were able to slim down without changing their diet, suggesting that bacteria may also play a powerful role in helping obese human patients lose weight.
In another study, published in Nature, scientists detailed how the typical Western diet containing high amounts of dairy and processed and sweet foods can change the mix of bacteria in the intestines of mice, setting the stage for colitis or irritable bowel syndrome. In gut environments with a large amount of milk-based fats, it turns out, certain bacterial strains that can cause inflammation tend to proliferate.
(MORE: Gut Bugs: They Are What You Eat)
In studies of human patients with particularly debilitating infections, including those involving Clostridium difficile — a hospital-acquired bug that causes diarrhea, cramping and potentially colitis (inflammation of the colon) — those who were given fecal transplants of bacteria into their colon from healthy individuals showed remarkable improvement. More than 90% of patients recovered from their infections and stabilized.
Based on the promising advances, researchers at many cancer hospitals are even banking the microbiomes of their cancer patients, who end up losing their helpful bugs during chemotherapy. Patients who receive their microbes back following the treatment tend to recover more quickly than those who don’t, suggesting that the right bacteria are critical for rebuilding and supporting a healthy immune system.
The real power of the microbes lies in their ability to mix and match. What the authors of the current papers learned was that although there is a staggering diversity of microbes that live within us, many perform similar functions. So while it’s difficult to identify any one group of bacteria that all people share in common, it’s not as hard to find various species that perform the same function.
It’s that commonality that scientists hope to exploit in developing future treatments or therapies for disease, by focusing on specific metabolic processes, rather than on trying to tease apart which of the 10,000 different species of bacteria does what. “The chemistry that these microbes can perform is mind boggling,” says Weinstock. “And not only does each microbe perform amazing chemistry, but they collaborate and create hybrid metabolic pathways, so the chemistry they can perform is more than just the sum of them.”
All of which argues for the fact that we should stop stereotyping all bacteria as bad. Some may be troublesome and potentially cause disease, but there are good guys among them, researchers say, and we should learn to become their allies. “The vast majority of microbes we encounter on a daily basis — far, far less than 1% — are pathogens,” says Proctor. “The vast majority are good bugs, and we want to support and feed our microbiome well.”