Digestion in a jar – Time to SHIME®

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In 2008, UGent spin-off ProDigest opened its doors. The company was built around a machine called the SHIME®, an in vitro model for the entire human gastrointestinal tract, complete with stomach and small and large intestines. The immediate interest from the food industry quickly made ProDigest a household name in its niche market. Since its establishment, ProDigest has significantly expanded its technology and activities and has taken on the pharmaceutical and veterinarian industries as additional partners.

Dr. Sam Possemiers is the proud managing director at ProDigest and has been involved since its conception. He witnessed the evolution of the technology and mediated its leap from the lab into the industry.

“I did my PhD at the University of Ghent, in the lab of Professor Willy Verstraete. During that time, we used a prototype of an apparatus that simulated the entire human digestive system in the lab. This allowed us to observe what happens inside the gastrointestinal (GI) tract without the use of animal models or invasive techniques. We could look at how different food ingredients are metabolized and what effect this has on the intestinal microbiota. It provided us with the means to closely study the relationship between food and health.

We knew that this technology had potential beyond scientific research, and there was great interest from the food industry to use our model of the human GI tract. We saw the possibility to build a company around this technology and created ProDigest. We fully automated our model and offered it as a research platform to the food industry and, later on, to pharmaceutical companies.”

(Re)creating digestion in a flask

The revolutionary machine was named SHIME® (Simulator of the Human Intestinal Microbial Ecosystem). To date, the SHIME® is the only in vitro model that simulates the stomach and small and large intestines in a single machine, incorporating its microbial populations. The creation of such a model is a feat that’s not to be underestimated.

“Establishing a technology such as the SHIME® demands a multidisciplinary approach. Knowledge of engineering is needed to design a mechanism with flasks, tubes, and pumps, and to incorporate features that regulate pH and also add various fluids, and so on. On the other hand, the complex microbiology of the human intestine needs to be understood, as does its physiochemical properties. Chemistry, biology, and engineering need to be combined to create a successful model. There are multiple universities conducting research into comparable models, but ours is the only one available for commercial applications.”

How are these digestive environments mimicked?

“If you want to simulate the entire digestive system, you need to take into account each aspect of it. A very important one is food and nourishment. A healthy individual eats three meals daily, so if we wish to reproduce digestion, our system also needs to eat three times a day.

Just like a regular human being, our SHIME® gets its breakfast, lunch, and dinner.

Next to this, we look at which parameters are important in each of the digestive organs. In the stomach, for example, gastric acids and secreted enzymes determine the physiological conditions. Also, time is an important factor, since these parameters don’t operate with an on/off mechanism but undergo gradual changes over time. The small intestine is where most of the actual digestion takes place. In this compartment, we add many digestive enzymes and fluids such as bile and pancreatic juice. Also, absorption of nutrients is simulated here. Finally, the large intestine is where the microbial presence plays a huge role. With the SHIME®, we can maintain these populations for extended periods of time, allowing long-term studies.”

The large intestine is where microbiota, host, and food all interact with one another. Most health effects for the host can be traced down to the large intestine, and this can be for better or worse. Colon cancer and improved immunity are just two examples of how these three elements can influence health.

Change as the only constant

ProDigest is growing and developing at an astonishing pace. While initially focusing on providing services for the food industry, different market branches, such as pharmaceutical industry and animal care, have opened up. While the activities and services of ProDigest continue to diversify, the technology behind the company continually expands and improves.

“When we stepped into the industry, it was important for us to remain independent of external financers. We were able to do this because, by providing services, we were profitable from day one. We started with the food industry, because it was quite accessible, certainly compared to pharma. In pharma, regulations are very strict and standards of quality and reproducibility are very high, so we included those companies later. We gradually expanded the company, not only in terms of capacity, but also in terms of activity. Today, we also have our own line of research, where we study various potentially beneficial food ingredients.
The SHIME® has evolved with the company. While our original SHIME® modeled the healthy, adult human being, we have expanded it to include babies, the elderly, and various disease models.  It really illustrates the versatility of our technology and how the SHIME® intrinsically has huge market potential.

We have even designed SHIMEs that mimic pigs, cats, and dogs.

We also added a mucus layer to the SHIME®, so we can study bacterial adherence to this layer. The next logical development was incorporating a cellular component. With this in mind, we designed the HMI (Host-Microbiota Interaction) module, a co-culture of human epithelial and/or immune cells with the bacterial populations present in the large intestine.”

Europe watches over you

The general public mostly remains skeptical on the subject of enhanced foods or food additives such as pro- or prebiotics. When asked what his stance is on this issue, Possemiers smiles:
“It’s a question I get a lot. I certainly believe that there are functional foods and specific ingredients that are beneficial for human health. On the other hand, we need to acknowledge that there are food products, mainly outside of Europe, for which there is no scientific evidence that they actually do the things that are claimed. Nowadays, the EFSA (European Food Safety Authority) is very strict with those things. Any food producer that wants to put health claims on their packaging or use health claims in marketing needs to provide fitting scientific proof for those claims. The EU implemented these measures to filter out charlatans and make room for products with proven beneficial effect. Many food producers come to ProDigest to collect scientific data to get the approval of the EFSA. These regulations assure the consumer that they aren’t being swindled.”

Thanks to ProDigest, food and pharmaceutical companies can make sure that their products are functional and safe, without troublesome in vivo testing. With its versatile technology suitable for many fascinating applications, it will definitely be interesting to see ProDigest evolve in the coming years.