Researcher evaluates traits in sorghum that affect the human gut

A professor at the University of Nebraska Department of Food Science and Technology is standing at the intersection of crop improvement and human health. Andrew Benson addressed the topic during the recent Center for Sorghum Improvement Seminar.

Benson, whose degrees are in microbiology, helped establish the Nebraska Food for Health Center and was named director in 2017. Its mission is to link agriculture and biomedicine through gut microbiome research. His current research program focuses on quantitative genomic analysis of traits in food crops, such as grains, pulses, and legumes, that have significant affects on the human gut microbiome.

He’s not a typical fit for a land-grant university, but he found his niche focusing on human health and disease prevention by working with those in agricultural production.

“The role of the Nebraska Food for Health Center was really to connect plant breeding, plant genetics and all the agricultural research capacity with biomedical research,” he said.

The question then became how is that done?

“Well, the human gut microbiome has a tremendous impact on health and wellness as well as disease predisposition,” he said. “The microbiome is involved in especially early-stage development of your immune system.”

The microbiome is involved in metabolizing dietary fibers, energy production for colonocytes, etc.

“A number of other beneficial metabolites are produced by the microbiome,” he said. “And essentially, abnormalities in species composition are associated with a wide variety of diseases.”

In some cases, dysfunction in the microbiome is known to be causal to the disease process. Benson said if a microbiome is taken from a diseased person and put into a germ-free animal, that germ-free animal will start taking on characteristics of that disease.

“It’s very clear that the microbiome was playing a very important role in our health and wellness and our susceptibility to diseases,” he said. “Preserving your microbiome and or restoring damaged microbiomes—that’s the link between agriculture and biomedicine.”

Biomedical research usually has nothing to do with agricultural research and vice versa and the two are normally “siloed.”

So how does genetic diversity within a crop species affect microbiome active components? Benson and his staff have done experiments with sorghum, maize and dry beans to try to figure this out. Sorghum was the first one “out of the gate.”

“It’s well known for diversity, fiber and polyphenols. A number of bioactives have been identified,” he said. “It’s consumed on a daily basis by certain global populations. (And a) crop that we can cultivate readily in Nebraska.”

They ran into their first challenge of the study—they can’t do human feeding studies. It’s way too impractical “for many, many reasons.”

In the sorghum study Benson and his colleagues started with a set of recombinant inbred lines. They took seed from each of those lines and put it through the AiMS system—milling the seed powder and through the in vitro digestion process.

“When we’re doing these pre-screening studies we chose one of the subjects that was sort of the average, that will kind of look like the average of what everybody looked like,” he said. “And that became the subject’s microbiome that we use for the genetic study.”

The plants were similar too—each grown in the green house and the team collected RGB data as well as other data from the limited tech system. After they had their replications and data collection complete, they measured a few things.

During the mapping experiment they noticed on the regions of chromosome two and chromosome four there was a fatale bacterium and several other organisms on there.

“We also had seed color that was segregating in this population,” he said. “And lo and behold, the seed color was also mapping to the same look at what those same loci on chromosome two and chromosome four, and we measure tannin content, and sure enough tannin content also mapped to those same peaks.”

What was interesting to Benson about this population was neither parent was producing tannin. Each parent carries a mutation in one of the tannin regulators.

“Oftentimes speaking to a microbiologist—we’re not used to segregation and multiple chromosomes,” he said. “With the Malian genetics, we do indeed generate tannin producing progeny out of that population. And sure enough, a quarter of the progeny are producing tannin from the real population.”

Researchers did a few more experiments and compared some other lines, but the one last step that really drove the nail in the coffin for them with the sorghum project was when they conducted molecular complementation. They put the microbiomes in minimal media so that there was very little for the organisms to grow on in the media.

“We added the pure tannins to that media and we monitored,” he said. “But across these four microbiomes that organism increase pretty significantly for a microbiome.”

They monitored for a specific organism and if put in a pure culture or just that organism, they got the same level of stimulation.

In the last experiment of the study, Benson had to convince his grad students to do it because “it’s a good old fashioned microbiology.” They took certain tannins and incorporated them into the solid media to get an organism to grow on solid media anaerobically.

“(We asked) can it actually degrade the tannins? Do we see zones of clearing and sure enough, you can get it to work,” he said. “You can see zones of clearing—those halos where it’s digesting and getting away. Getting rid of that brown color tannins.”

It was pretty compelling evidence all the way down to the mechanistic level that the organism is at least degrading the tannins and appears it’s able to grow in them.

“That explains what we’re seeing in vitro all the way back to the causal genetics and the causal variants that were driving,” he said. “So we got lucky in this paper. Lucky to hit the tannin loci because it was easy to go after. And it provides very compelling evidence that this approach really works. So we’re really excited about that.”

Human consumption

How does this all relate to the real world? There’s not a lot of sorghum consumed in the United States, and Americans could stand to eat a lot more, Benson said. Sorghum, however, is a major staple of the diet in sub-Saharan Africa. There’s a paper that looks at bird pressure and tannins. Authors noted that in a mapping population birds would feed in certain areas.

“But they were fairly selective on what lines they were feeding on,” he said.

In the wild, the birds were actually feeding on a certain phenotype, and the damage was pretty clear. Research and genetic analysis found there was a genetic association with the height of the panicle and tannin production.

“So the birds tended to favor chewing on things that had high panicle height, and low tannin production,” he said.

There’s a specific species of bird in Africa that likes sorghum particularly. Benson said they swarm in like locusts and can destroy a crop in a very short period of time depending on where it’s located. Location also dictates whether the grower is producing low tannin or high tannin sorghum—high tannin where there’s a high population of these birds and low tannin where there’s a lower threat.

“It really starts to make me question if the birds are driving the breeding programs and driving which lines are being produced where we go,” he said. “Believe it or not, there’s also a phenomenon associated with that in the segregation or at least it appears that the stratification of the human population because the human populations that are growing in areas where they’re producing high tannin sorghum also have a higher frequency of the non-bitter tasting allele for the taste receptors.”

People in these areas are unable to taste bitter tastes as easily, which makes them more likely to be able to consume the high tannin sorghum.

“Now we know that tannins also have a whopping effect on the microbiome and it makes you ask the question, are there potential microbiome differences in the individuals in these regions, essentially driven by the bird populations that drives the breeding and growing. Drives what they’re eating on a daily basis?” Benson said.

Beneficial microbes that tend to preclude or reduce susceptibility to a number of diseases are important in these instances, and he’s fascinated to look at these things. His first study is not yet published and the data is “rolling out the door,” he said.

At the center, researchers have looked at several other major traits—waxy in sorghum, quality protein trait in maize (popcorn). Both of those have a whopping effect on the microbiome, according to Benson.

“So I think this is going to be a new direction. And the idea is how do we as an entire community, think about actually incorporating these into breeding programs? When does it make sense? What are the best traits to go after? How can we create value from the streets so that we can commoditize it or commercialize it and get it into the commercial stream?”

For more about Benson’s research visit https://foodforhealth.unl.edu/.

Kylene Scott can be reached at 620-227-1804 or [email protected].