The human gut contains a small army of bacterial workers that can benefit human health. These workers are part of the gut’s microbiome—all of the microbes that live inside that part of the human body. It’s up to us whether we starve them or feed them, based on the foods we eat.

“There are trillions of microbes – bacteria, viruses, fungi and more – living in the gut, and they aren’t just along for the ride,” said Andy Benson, a microbiologist and director of the Food for Health center. “The gut microbiome acts in concert with the body to regulate organs, develop our immune systems, fight disease and metabolize foods.”

“There are trillions of microbes—bacteria, viruses, fungi and more—living in the gut, and they aren’t just along for the ride.”

Establishing what constitutes a healthy microbiome is important because high or low microbial diversity can have different implications for health or disease, depending on the body site. For example, low microbial diversity in the gut is associated with obesity, inflammatory bowel disease and Crohn's disease. The goal: to increase the diversity of the right kinds of microbes.

Feeding Your Body, Feeding Your Microbiome

Abnormalities in the gut microbiome are being discovered as factors in many diseases, and diet is a known factor that can cause or exacerbate abnormalities in the gut microbiome. Because microbiomes are fed by the same foods that we eat, researchers like Benson can develop foods with enhanced levels of health-promoting ingredients. These ingredients work by selectively feeding beneficial microbes or prohibiting growth of more harmful species.

“This new interface between agriculture and medicine holds tremendous potential to transform how we think about preventing and treating disease,” said Benson. “If a gut’s first resident microbes really do influence which microbes come, stay or go, then early-life factors that contribute those microbes—like c-sections, antibiotic use, infant formula, and early life diets—could have prominent health consequences years later.”

“The question now becomes, how do we use diet, early or later in life, to prevent or mitigate damage to the microbiome?”

The Nebraska Food for Health Center, a multidisciplinary research center based at the University of Nebraska-Lincoln, connects strengths in agriculture and medicine from across the four-institution University of Nebraska system. The center links gastrointestinal and biomedical research to agriculture, plant and animal breeding and genetics. In addition to faculty at the University of Nebraska–Lincoln, the team includes faculty from the University of Nebraska at Omaha and the University of Nebraska Medical Center.

They conduct research to develop foods with proven health benefits, particularly those that affect the human gut microbiome — the collection of all the beneficial and potentially harmful microorganisms in the digestive system that can affect health and well-being.

“Our focus is on developing hybrid crops and foods that improve the quality of life of those affected by critical diseases—including heart disease, diabetes, obesity, cancers, inflammatory bowel disease and mental disorders,” explained Benson.

Improving Human Health

To launch the center, the Raikes Foundation of Seattle, co-founded by Nebraska native Jeff Raikes and his wife, Tricia, committed a $3 million gift to the University of Nebraska Foundation. In recognition of Jeff Raikes’ service as chief executive officer of the Bill & Melinda Gates Foundation, the Gates Foundation also made a $2 million gift in support of the center.

“This critical effort will further define Nebraska as an agricultural leader,” Raikes said. “For the first time, It brings together agricultural production, food processing and medical research to improve the health of people in this country and around the world.”

The Raikes gift helped fund two of the robotic systems that Benson uses in his genetic analysis of crops for microbiome activity. The machines allow them to screen hundreds to thousands of genetic lines of crops for their ability to affect the human gut microbiome. Hundreds of vials each contain grain from different genetic lines of a crop and a robotic arm feeds each vial into a mill, which grinds it into a very fine powder that represents chewing.

After the grain is ground up, researchers use a second machine to dispense small amounts into individual test tubes. Finally, each individual test tube is treated with acid and enzymes to mimic digestion, followed by introduction of all of the tubes into an anaerobic chamber, where another machine automates feeding of human gut microbiomes to the grain. The combination of machines is unique to Benson’s lab.

The Food for Health Center looks to identify what traits matter in food crops; then demonstrates clinically how those traits can prevent or minimize disease. Their researchers begin by looking at hundreds of thousands of genetic lines of grains and beans to define the microbiome-active traits they display. The changes that occur in the microbiome are measured by DNA sequencing of the entire microbial community.

When specific genetic lines of a grain have positive traits for beneficial microbes, a Food for Health plant breeder next grows large quantities of these lines to use in pre-clinical trials and human clinical trials. When the food lines identified are taken to clinical trials and finally to market, the potential impact on human health could be transformative.

A Background in Microbiology

Benson has spent a lifetime studying tiny organisms. It began his senior year in high school, when he took physiology and became transfixed by bacteria. His freshman year at Iowa State University, Benson took a 300-level microbiology class and knew it was his calling. He switched from a med tech major to majoring in microbiology—and hasn’t looked back since.

His sophomore year, he began work in a microbiology lab at ISU to put himself through school. His time in this unique environment, surrounded by graduate students who served as mentors, made a deep impression on him. “I’m getting a Ph.D. and becoming a professor,” he told his college girlfriend, who he later married. Benson entered into a Ph.D. program immediately after graduation, studying with a prominent bacterial geneticist at the University of Texas.

When the Food Science department at UNL started looking for a microbiologist and geneticist to look at food safety and food-borne pathogens, Benson found a home that would eventually turn into his role leading the Food for Health center.

For the first ten years at UNL, he focused on genetics of food-borne pathogens. But in 2007, new DNA sequencing technology became available that transformed scientists’ abilities to study entire microbial ecosystems. Before that, the gut biome had been a black box, with no real methodology to study the complex community of microbes.

Benson used this new technology to study how individual genetics impacted the microbiome in the gut, but realized that diet could overwhelm genetics. Rather than studying genetics in the host, Benson started studying genetics of the food crops that are ingested by the host—and how plant genetics can affect the gut microbiome. This decision positioned him as an expert at the crossroads of agriculture and medicine.

Creating Better Crops—And Bringing them to Market

“Why start a center like Food for Health in Nebraska? Because we're an agricultural state; we’re major food producers,” said Benson. “That's why our researchers are looking at food through the lens of health. We should be the ones to do this. The state should be known for food innovation.”

“Nebraskans can buy into being innovative and transformative using food. We're good at growing grains. And the right grain can make not just Nebraskans, but Americans and the world healthier. That's what I'd like the center to be known for—making humans healthier by creating better crops.”

Benson believes there's a benefit in terms of providing new avenues for revenue for farmers. If they grow a crop that has unique microbiome active traits—traits that are proven to benefit human health—markets can be created that will deliver an enhanced return on that crop. It gives farmers another option—and one that will impact health across the world.

Along with potentially creating an economic impact for farmers, Benson and his team have the opportunity to commercialize their research. Nebraska Innovation Campus—where the Food for Health Center is located—is the ideal ecosystem where big companies can be matched with faculty research partners and startups. “What will incentivize big partners to come are spinoffs who’ve taken some of the risk and raised commercialization to a level where the big companies are willing to buy,” said Benson.

Benson has already created a startup, Synbiotic Health, that is developing and commercializing proprietary combinations of probiotics and prebiotics with proven effects on the microbiome—and accompanying health benefits. They’ve hired two Ph.D.s, one of whom is a recent graduate. And the company has the potential to grow into a much larger one.

“There's a lot of big fish that want to buy us already,” said Benson. “But not yet. Just let us grow. Let us grow.”