To pore through a list of Rob Knight’s publications is overwhelming. The topics jump from lake sediments to pulmonary hypertension, and they span the globe from the Tibetan Plateau to the Midwestern United States. A professor in the Department of Chemistry and Biochemistry, and a BioFrontiers faculty member, Knight walks, talks and lives at a rapid-fire pace because he is a busy researcher, and because he will never have enough time to tell you all he knows about the microbiome.
The microbiome is made up of microbes that live on us and among us. Scientists are becoming increasingly acquainted with the 100 trillion or so microbes that live on and in our bodies. In fact, these bacterial cells outnumber our human cells by 10 to 1, which means you can say you are more bacteria than you are human. Knight was part of the Human Microbiome Project Consortium that genetically sequenced the microbial mosaic of 300 healthy humans. What Knight is finding is that the microorganisms in our bodies make us more unique than our genes do.
For those just getting up to speed on the small universe taking up residence in our bodies, here are five things Knight wants you to know about the microbiome:
The microbiome is more important than you think.
Becoming friendly with the microorganisms living in and on your body should be fairly easy. They live in your gut, ears, mouth, nostrils and even your inner elbows. There are more than 400 known bacterial species in the human microbiome, which also includes viruses and fungi. The microbiome has been linked to a broad spectrum of diseases, from diabetes to depression. Influencing bacterial communities to support your health goals is a challenge, but might be easier than somehow modifying your genes to get the disease-free life you are after. Knight knows it is time to build some alliances with about 100 trillion new bacterial friends.
Each of us is as diverse as our microbiome.
Our own personal collection of bacteria is unique, with the similarities between any two people being only about a shared 10 percent. A similar genetic background might give you more common ground, but diet, environment, genetics and early microbial exposure can add variety to your personal universe.
Variety being the spice of life, the more diverse the community of bacteria, the better your health. Having little diversity in the microbial population in your gut, for example, could indicate problems with obesity or inflammatory bowel disease. In the gut, microbes break down vitamins and tough plant cells and extract valuable nutrients to deliver to your body. The more diverse your digestive team is the better.
“This is the Holy Grail of personalized medicine, “ says Knight, describing how drugs can be tailored to respond to specific bacterial communities to increase their effectiveness. “We’re finding that optimizing the microbes you have may be even more important than optimizing your lifestyle.”
The microbial communities living within our bodies undergo rapid and dramatic changes in early childhood.
The easy answer to harnessing the power of the microbiome for better health is to cultivate a healthy one in the first place—in childhood. Part of the process of being born installs some of the healthy bacteria babies need, as they travel through the birth canal and into the world. Babies delivered via C-section may miss out on some of this. Breastfeeding will also supply youngsters with healthy microbes. Exposures to new foods, new environments and new illnesses all help babies grow their own unique microbiome.
In the first few years of life, babies go through a rapid overhaul of their gut microbial communities. Some of these changes can impact human health 60 or 70 years down the road. It seems the message new parents get about disinfecting everything in their baby’s world may not be entirely correct. Some of the best opportunities for creating a healthy microbiome could seem counterintuitive.
Tasked with parenting his own young human at home, Knight pauses for a minute when asked how he is helping his daughter develop a healthy microbiome. “Letting her play outside is important . . . fresh air and grass and dirt. And we have a dog.”
The long-term effects of antibiotics on gut microbial communities needs to be addressed.
Antibiotic medications are designed to kill dangerous bacterial colonies, but they are indiscriminate about it. These drugs are life-saving for people with very serious infections, but they also significantly impact the nature of the body’s microbiome.
Today, more antibiotics sold in the U.S. are used in animals. Most are administered through their food and water, versus through an injection, indicating that they are not being used to treat a specific illness in a single animal. Antibiotics were used originally to keep animals in close quarters healthy, but farmers quickly noticed additional benefits: rapid animal growth and increases in fat mass.
Knight’s lab is working to understand how antibiotics are impacting human microbial communities and our propensity for obesity. In addition, widespread use of antibiotics has contributed to the rise in antibiotic-resistant bacteria like MRSA and drug-resistant tuberculosis. An estimated 99,000 people die each year from hospital-acquired infections, most of which come from antibiotic-resistant bacteria.
“We are only now understanding the impact of antibiotics,” Knight says. “We now need to figure out how to balance the necessity of antibiotics with the harm those drugs do to beneficial microorganisms.”
Studying these small organisms requires big computing power
Knight’s genre of study is often called “Big Data” for good reason. Genetic data requires massive computing power, big storage and tons of computer coding.
“Big science is hard. Metagenomic science is hard. And metagenomic, big science is the square of hard," said Doyle Ward, a scientist at the Broad Institute, in the institute’s online newsletter.
Knight is constantly on the hunt for bigger and faster computing power and the expertise it takes to look across huge datasets for patterns. At the BioFrontiers Institute, Knight shares a lab with biologist, Robin Dowell and computer scientist, Aaron Clauset. All are working on big data projects and understand the need for effective analysis of huge sets of data. For example, a single flow cell used in genetic sequencing, about the size of a microscope slide, can generate in the neighborhood of 300 gigabytes of data. Never before, has computer science been such a good job prospect for college graduates, especially bioinformatics: a hybrid of computing and biology.
“As an undergraduate, I was told there was no career future in combining biochemistry with computer science, and that I should take ‘more useful’ courses like organic chemistry and genetics,” says Knight. “It was in grad school that I realized computer science was necessary and I picked up those skills on my own.”
Undaunted by the challenges of big data science, Knight is seemingly everywhere, sequencing the world around him. A Google image search shows him gingerly approaching a komodo dragon at the Denver Zoo, armed with a testing swab. Another shows the Knight family Labrador, Wash, unsure about having his tongue sampled. At the moment, Knight is participating in microbial-related research in Malawi on malnutrition http://blogs.discovermagazine.com/notrocketscience/2012/05/09/three-nations-divided-by-common-gut-bacteria/#.UUot3HDmpN0, and in the crowdfunded “American Gut” http://www.indiegogo.com/projects/american-gut program to study our gut microbial communities stateside.
His sense of scientific urgency aside, Knight reflects on the impact of his research. “It is such an exciting time,” he says. “We are uncovering how valuable this microbial world is and figuring out creative ways to use new tools to solve problems. Part of our job now is to inspire the next generation of scientists to take the tools and make new discoveries. There is far too much here for one lab to take on.”