NIH awards new research grant to unlock the gut microbiome’s impact on human health

06 Feb 2024 --- The US National Institute of General Medical Science, part of the National Institutes of Health (NIH), has awarded a US$1.9 million five-year research grant to help understand how complex communities of microbes impact human health. The Maximizing Investigator’s Research Award has been granted to Jordan Bisanz, assistant biochemistry and molecular biology professor at the Penn State Eberly College of Science.

A person’s microbiome may contain several hundred or thousand different species. While research on microbiome diversity is expansive, more research is needed to detail the processes where the microbiota impacts human health. 

The grant will enable the researcher to understand better how microbial communities shape human health and physiology. By building a model of a healthy microbiome, Bisanz will examine how the gut responds to disease and infection and explore how to improve the absorption of medications. 

“The microbiome is very responsive, and it can be modified quickly and easily using dietary manipulations, like probiotics,” he details. “It is a relatively young field but has promising and immediate translational applications.”

Healthy microbiome 
Bisanz aims to use computational methods to analyze publicly available data on the human microbiome from a wide range of available studies focusing on identifying microbiome diversity — number of species present — individual species and their abundance. 

“It is clear that the diversity of microbes in the human body is important, but why that diversity is important gets much murkier,” explains the researcher. 

“We plan to use a combination of computational and experimental biology to understand better the different species that make up a healthy human microbiome as well as how they work together to impact human health.” 

He details that the team will look at information from hundreds of people to identify the most common strains or combinations of strains in a healthy microbiome. 

“Then, we can design a healthy microbiome and use that as a model system to understand how the community functions. This is a very different approach from how microbiology tends to be done.”

Laboratory model  
The project’s next phase will be to experimentally build a laboratory model of a healthy microbiome, selecting strains from the several hundred microbial strains maintained in the lab. 

With this model, the research team can assess how the microbiome might respond to a specific disease or identify and build models of microbiomes that reflect those of people with a particular illness. 

With a healthy microbiome model, the research team can assess how the microbiome might respond to a specific disease.“It’s kind of like a cookbook of microbial communities, and we can decide what is practical for us to use to explore different questions,” illustrates Bisanz. “Ultimately, we hope to better identify the specific microbes and metabolic processes important for host-microbe interactions and how they impact disease risk.”

He adds that such specific microbiome models may also help develop targeted therapies that use particular microbes to improve gut health or treat bacterial infections. 

Personalized medication 
In addition, Bisanz aims to determine how the microbiome impacts a person’s medication response. He highlights that the microbiome can impact absorption efficacy as oral drugs typically pass through microbes before they are absorbed. 

“One of the questions from a personalized medicine standpoint is how to select the right drug dosage,” he highlights. “You can imagine in a futuristic world, you might go to the doctor for a treatment, and they could do a quick test. And maybe they would identify a genetic marker that indicates you absorb the drug more quickly than others and identify that they have a microbe known to metabolize the drug, and that helps them set the dosage.”

One medication area that the team will focus on is the uptake of orally administered antimalarial drugs, which are associated with side effects ranging from dizziness and vomiting to lucid dreams. 

“There is a huge amount of unexplained variation in the amount and severity of these side effects, and a lot of people stop taking the drugs because of those side effects,” Bisanz underscores. 

“Antimalarials are also a subject of concern because there is increasing resistance to the most common drugs in the parasites that cause malaria. If microbes can impact how much of a drug gets into the bloodstream, they may also influence the side effects, and it’s reasonable that they may also be playing a role in developing resistance.”

Gut microbiome research 
Studies on the gut’s diversity and its impact on human health proliferate. For example, researchers found that people living with Social Anxiety Disorders have a different microbiota composition than healthy individuals. Inserting microbiota from affected patients into the guts of mice increased the animals’ sensitivity to social fear, changes to stress and immune functions. 

Moreover, Austrian scientists revealed that eating fruit and vegetables contributes to gut bacterial diversity, noting that this diversity is essential to human health. 

Also, US-based researchers suggest that microbiome-directed complementary food could benefit malnourished kids, explaining that these foods help repair the gut microbiome better than traditionally used therapeutic foods. 

Meanwhile, Nutrition Insight talked to probiotics pioneer Yakult about the modern research perspective on the gut microbiome, microorganisms and their role in overall health. The company has joined four substantial microbiome R&D projects, aiming to make dietary microbes an official food category. 

By Jolanda van Hal