New technologies have revolutionized the way we see and understand the human microbiome: the approximately 100 trillion bacteria and other microbes that live in and on the human body. Most of these microbes do not cause disease—indeed, humans rely on these organisms to perform vital functions. In the coming decades, clarifying the many roles of the microbiome will dramatically reshape medicine and public health. Curtis Huttenhower, associate professor of computational biology and bioinformatics, describes the changes ahead.
The biggest advance in studying the microbiome is that genetic sequencing has become cheap. And there are now other molecular technologies that complement DNA sequencing, like looking at microbial small molecules or having easy, high-throughput ways to get a variety of different microbial community samples, to grow or isolate microbes. Everybody’s strain of every bug is a little different.
These discoveries suggest possibilities at both the large population-scale end and the precision- or personalized-medicine end. At the population scale, one of the goals is to learn which exposures create the huge diversity in the microbiome that we observe. If you think about human genetic studies, we share 99.9-plus percent of our DNA, so the last few variants are really important. But we share at most 10 percent of our microbial species. And much of that diversity is probably health-related. I could have a bug that makes me more or less prone to a particular disease than other people. But right now, we don’t know where that population-scale diversity comes from: early life exposures, physical environment early in life, whether we’re exposed to livestock or pets, what our first foods are, how our immune system develops, what medications we’re exposed to.
At the population scale, there’s the opportunity to understand this variation and then put in place best practices for public health to support the right kind of microbiome development. There’s a lot of dialogue now around things like understanding how or when best to use antibiotics in early life. All of the things that I just said about early life also apply to healthy aging and maintenance of the immune system late in life. The timing or the specific types of antibiotics early in life may influence the developmental trajectories of the microbiome. In a 30-to-50-year time window, we will have a much better handle on which large-scale public health practices support the development and maintenance of a healthy microbiome.
On the individual scale, we’re starting to find the right combination of organisms to support or fix gut health. Extend that 30 to 50 years, and we’re talking about reading out an individual’s microbiome, figuring out the right bugs or the right nutrients to maintain health, or making the right perturbations to the system—either adding bugs or removing bugs, or adding a pharmaceutical or an antibiotic.
Imagine being able to ensure that an infant’s microbial development prevented him or her from developing allergies or autoimmune disease, type 1 diabetes, rheumatoid arthritis: long-term, chronic conditions that are immune-linked but not infectious or pathogenic. These conditions interact with microbes, but right now they’re not something we can treat by destroying a particular bug at a particular time. The same approach applies at the other end of life for healthy aging. Parkinson’s disease, multiple sclerosis, and other neurocognitive or neuromuscular conditions have strong microbiome associations—but all we have is associations. In 30 or 50 years, I believe we will have enough evidence to act.
Photo: Kent Dayton