In Good Company

A balanced diet that is rich in fiber is known to be a precondition for this equilibrium. When fiber is broken down by bacteria inside the large intestine, one of the substances that are generated is butyrate, a short-chain fatty acid that plays a special role. tom Dieck and her team took the following insight as their starting point: “Butyrate provides most of the energy that is needed by some intestinal cells. Scientific studies have shown that this substance is essential for a healthy intestinal mucosa and an effective local immune system.” If there is a lack of butyrate in the intestines, it is difficult for the intestinal mucosa to fulfill its function as a protective barrier.

Using this approach, the research team found a way to increase the formation of butyrate by the intestinal bacteria by bringing together a live probiotic bacterial strain and a protein component. Tests have shown that each ingredient used by itself already boosts the formation of butyrate by the bacteria, says tom Dieck. “However, when the ingredients are used in combination they have an even bigger effect,” she says. Experts call this kind of synergetic interplay “synbiotic.”

This research-based development has now led to an innovative system solution for business customers who want to market applications for maintaining gut equilibrium. “In addition to the research, we provide all the ingredients as well as target group-specific positioning,” says tom Dieck, who is the head of research and business development for synbiotics at Evonik. “The  advantage provided by our formulations is that they enable companies to make not only innovative combinations but also reliable assertions about a specific health benefit—in other words, health claims—in their communication with consumers.”

The colleagues researching the microbiome and gut health in the district of Halle-Künsebeck in Westphalia, Germany, are playing an important role in the development of synbiotics. The microbiologist Prof. Stefan Pelzer has been researching microorganisms in the digestive tract since 2013. His focus was initially on the question of how livestock can be kept healthy and productive without antibiotics. Today his team is also researching the human microbiome—inside the gut and on the skin.

“Today scientists are discovering that about 90 percent of all illnesses have a connection with the gut microbiome,” he says. The number of bacterial cells in the human body exceeds the number of the body’s own cells by a factor of 1.3—and most of these bacterial cells are located in the large intestine. This might make some people feel uncomfortable. But according to Pelzer, it would be disconcerting if the opposite were the case. “The composition of the microbiota—in other words, the assemblage of microorganisms—is altered by many illnesses as well as by the aging process,” he says. “Specifically, the diversity of the gut bacteria decreases.” This occurs alongside a loss of the products of bacterial metabolism, such as butyrate, that are necessary for human health. “Researchers are increasingly documenting the fact that a decrease in the diversity of the microbiome has a negative effect on the body’s fitness and its resistance to infection,” Pelzer explains.

Consequently, those who aim to enhance high performance and resilience in human beings and animals often do so by adapting the microbiome—for example, by means of probiotic products, which contain live bacteria. These products generate multifaceted momentum, either directly by forming substances such as lactic acid or indirectly by influencing the composition of the microbiome.

All of these questions can be answered by means of genome sequencing. In this process, all the genes in a bacterial sample taken from the gut model are analyzed. “Twenty years ago, this kind of analysis would have cost tens of thousands of US dollars and required many months of work,” says Pelzer. “Today we can get this analysis done for a few hundred dollars in a few weeks. For very specific inquiries, we can even get it done on site in real time.”

Computational biologists can use these data to create a rough picture of the distribution of the existing groups of bacteria and to identify possible changes. They can even use the gene sequences to find out what capabilities a microbiota has—for example, whether it is producing certain metabolites, which are  the intermediate products of a biochemical metabolic pathway.

The expertise gained in Halle-Künsebeck can flow into the development of new probiotics for human beings and animals. “By now our models are so good that they enable us to make very reliable predictions about our products’ behavior in a living organism,” says Pelzer. That speeds up the development process and reduces the need for tests in live animals.

This is also true of the synbiotic product concepts that Heike tom Dieck and her team are pursuing. The initial findings came from stool samples that had been cultivated together with bacterial strains and selected substances. Next, they investigated how the microbiota composition had changed and what metabolic products were present. “Even in this simple model we already saw clear effects on some substances and some bacteria,” says tom Dieck. “The composition of the microbiome changed, and we found more butyrate.” For some combinations of a bacterium and a substance, the effect was even more intense.

The synbiotics researchers used a model similar to the chicken gut model in Halle-Künsebeck to precisely understand the behavior of the capsules containing the bacterium and the dipeptide in the human digestive tract. They showed that the bacterium and the dipeptide reach the target destination in the large intestine, and that their arrival correlates with an increase of the local butyrate-forming bacteria. This has now been confirmed by a small pilot study in human beings.

However, for the research teams at Evonik this topic is still far from being exhausted. They are continuing their work on further probiotic and synbiotic developments. The individualized nature of the gut and its equilibrium leads to many further questions. For example, are there ways to determine the current status of an individual’s gut—and to make a targeted and individualized intervention with the help of microbiota? If this approach succeeds, it will open up many new opportunities for research and practical applications.