Bacteria and microorganisms living in the human body -; Microbiota -; It can affect people’s health, disease risk, and even how the body absorbs drugs, but the details of these processes are unclear. To help understand how complex communities of microbes affect human health, the National Institute of General Medical Sciences at the National Institutes of Health has awarded a 5-year, $1.9 million Maximizing Investigators Research Award to Jordan Bisanz, assistant professor of biochemistry and molecular biology at Penn. State Eberly College of Science.
It is clear that microbial diversity is important in the human body, but why that diversity is important becomes more unclear. “We plan to use a combination of computational and experimental biology to better understand the different species that make up a healthy human microbiome, as well as how they work together to influence human health.”
Jordan Bisanz, Assistant Professor of Biochemistry and Molecular Biology, Penn State Eberly College of Science
A single person’s microbiome may contain hundreds or thousands of different species, for example living in the digestive tract or on the skin. Many microbiome studies focus on counting the number of different species present -; Diversity -; as well as identification of individual species and their abundance. Bisonz plans to use machine learning and other computational methods to analyze this type of publicly available data to better understand what defines a healthy microbial community.
“We plan to look at data from hundreds of people to identify the most common strains or combinations of strains in a healthy microbiome,” he said. “Then, we can basically design a healthy microbiome and use it as a model system to understand how the community works. It’s a completely different approach than how microbiology is done.”
After identifying key species in a typical healthy microbiome, Bisanz and his lab will experimentally create a laboratory model of a healthy microbiome, drawing from the hundreds of microbial strains they maintain in the lab. Then, they can assess how that microbiome might respond in the context of a particular disease. They can identify and create laboratory models of microbiomes that mirror those of individuals with specific diseases.
“It’s kind of like a microbial community cookbook, and we can decide what would be practical for us to explore different questions,” he said. “Ultimately, we hope to better identify specific microbes and metabolic processes that are important for host-microbe interactions and how they influence disease risk.”
This work could help develop targeted therapies, Bisanz said, that use specific microbes to treat bacterial infections or improve gut health rather than a more general set of microbes, such as probiotics and fecal transplant therapy.
Bisanz will also explore how the microbiome can influence a person’s response to drugs. Most drugs taken orally pass through the gut before being absorbed into the body, he says, so the gut -; Like host genetics -; Can affect how effectively and efficiently drugs are absorbed.
“One of the questions from a personalized medicine perspective is how to select the right dose of a drug,” he said. “You can imagine in a future world, you go to the doctor for a treatment and they do a quick test. And maybe they’ll identify a genetic marker that indicates that you absorb the drug more quickly than others and detect that too. can make sure they’ve taken the drug. A microbe that’s known to metabolize the drug, and that helps them set the dose.”
Bisanz and colleagues will specifically investigate the role of the microbiome in taking orally administered antimalarial drugs, which are notorious for their side effects that range from dizziness and vomiting to vivid dreams.
“There is a great deal of unexplained variation in the amount and severity of these side effects, and many people stop taking the drug because of those side effects,” Bisanz says. “Antimalarials are also a concern because resistance to the most common drugs among the parasites that cause malaria is increasing. If microbes can affect how much of the drug enters the bloodstream, they can also affect side effects, and it’s reasonable that they play a role in the development of resistance.”
Together, this grant will allow Bissanz to advance understanding of how microbial communities shape human health and physiology.
“The microbiome is very responsive, and it can be modified quickly and easily using dietary manipulations such as probiotics,” he said. “This is a relatively young field, but it has promising and immediate translational applications.”