WUR investigates what best to feed your microbiome

Everything we eat travels through the stomach to our intestines. Whatever the body does not absorb passes through to the microbiome. It is therefore no surprise that diet influences our gut microbes. Yet we still know little about how most ingredients affect individual bacteria or the composition of the microbiome as a whole. WUR researchers are working to unravel these interactions and discover how diet can promote a healthy microbiome. Here, we highlight seven pressing questions on this topic.

A healthy microbiome is hard to define. Researchers estimate that a person’s gut contains around 350 different microorganisms, but everyone has a unique composition. If you compare the microbiome of five hundred people, you will not find a single microorganism that occurs in all of them. What matters most are ‘anomalies’. Research has linked certain microorganisms to health and disease. Enterococcus faecalis, for example, regularly occurs in people with liver disease, while Akkermansia muciniphila is associated with good gut health. Moreover, specific bacteria are conspicuously absent in certain diseases. 

Diversity matters, too. Broadly speaking, the greater the variety of microorganisms, the more stable the system. Together, they protect the gut from pathogenic intruders. Each microbe has its own way of doing this. Some consume nutrients that pathogens would need to survive, while others produce compounds that kill harmful microorganisms.

That is the current hypothesis and precisely what our researchers are studying: how can diet influence the composition of the microbiome? Probiotic yoghurt drinks, for example, deliver live microorganisms to the gut. However, WUR’s research also focuses on how nutrients stimulate the growth of beneficial microorganisms that are already present in the gut. We call these prebiotics. At WUR, we investigate how food ingredients affect the microbiome at various levels. For example, we study which dietary patterns increase the diversity of microorganisms in the gut, as well as how bacteria in the colon break down dietary fibre and how that affects their growth.

WUR uses various methods to study changes in the microbiome, ranging from simple laboratory tests to sophisticated studies involving human participants. One of the simplest screening methods involves placing a small amount of stool in a plastic plate with tiny wells. The stool provides an imprint of the gut microbiome. Researchers add a food ingredient and investigate what happens to it. At the same time, they examine how the microorganisms respond, which substances they produce and whether these are beneficial for our health or potentially toxic.  

Researchers also work with an in vitro model: an artificial gut system. Although it may sound graphic, the system does not look much like the human digestive tract at first glance. It consists of a cabinet with tubes, vials, syringes, and pumps. Microorganisms that naturally live in the human colon grow inside the system. The system also mimics our intestines in other areas: from the peristaltic movements to mix and propel the digested food pulp, to our body temperature and the acidity of the colon. Several versions of artificial intestines already exist. At WUR, researchers are developing a new, improved version by combining existing technologies. They call it TIMOTHI, short for The Incredible Mimic Of The Human Intestine. The system is fed a range of ingredients that would also reach the colon in humans.   

The colon is one of the last stops in the digestive system. The stomach kneads the food into a thick mixture and the small intestine breaks down most proteins, fats and some carbohydrates and absorbs vitamins and minerals. What remains includes indigestible dietary fibres (carbohydrates from plant products), sweeteners and non-degraded proteins. We feed the artificial gut a similar mixture. We then study the composition of the microbiome before and after feeding the test ingredients to the artificial intestine. This helps us understand how these substances affect the microorganisms and the composition of the gut microbiome. For example, we have learned that plant proteins that the small intestine does not fully break down can be turned into toxic substances by gut microbes.

Two important developments are DNA sequencing and the miniaturisation of chemical analysis. In the past, researchers had to culture microorganisms in the laboratory to identify them. Today, they can read their DNA directly. Advances in technology have made this process much faster and cheaper, allowing researchers to identify which microorganisms live in the gut. And thanks to modern analysis, we can tell with just a few micrograms of nutrient which substances are released during digestion.

There is still a great deal we do not know. That is partly because it is really difficult to culture gut microorganisms in the lab. Some are highly sensitive to oxygen, since they naturally live in the largely oxygen-free human colon. But we need to culture microbes to really understand what they do. DNA analysis can help researchers identify around seventy per cent of microbial functions. DNA contains the instructions for producing proteins and these proteins determine exactly what a microorganism does in its environment. Unfortunately, DNA does not tell us everything, even though there are developments there too. Artificial intelligence helps scientists to predict the three-dimensional structure of proteins based on the DNA sequences, potentially helping researchers infer protein functions. This opens new doors for our understanding of microbial systems.

WUR offers companies various ways to test how their food products affect the microbiome. These range from simple laboratory screenings and experiments using the artificial gut TIMOTHI to clinical studies. Computer tools and visualisations help researchers interpret the results and understand what is happening. Companies do not necessarily have to start at the beginning of this research pipeline. They may already have conducted their own research and choose to join at a later stage. In a clinical study, for example, researchers can investigate the effect of a dietary fibre on healthy people or people with irritable bowel syndrome. 
WUR recruits the participants and conducts the study. One group receives a placebo, while the other receives the product being tested. Ideally, the study uses a crossover design, in which each participant receives both treatments and serves as their own control.