In and on the human body, there are approximately one hundred billion microorganisms, i.e. hundreds of various types of bacteria, fungi and viruses located on the skin, in the mouth, in the vagina and, particularly, in the intestine. The collection of all these microorganisms constitutes the microbiome. ‘A human body contains as many bacteria as human cells.’
The microbiome has several important tasks. It digests our food, builds up amino acids, vitamins and short-chain fatty acids important to the intestinal mucosa and trains our immune system. ‘The microbiome is vital in terms of offering protection against microorganisms from outside the body’, Weersma says. However, if the system gets out of balance, a pathogen may attack more easily. ‘Microorganisms are located on various parts of the human body. As a result, pathogens are less able to intrude. However, should a pathogen be able to do so, the immune system offers adequate protection. In this way, the microbiome and immune system jointly offer us protection against infectious diseases’, Weersma says.
The microbiome composition varies between people and over time. Research conducted at the UMCG demonstrated that this may be due to medicine use, for instance. ‘This not only goes for antibiotics, but also for a specific type of antacids called proton pump inhibitors.’ This is among the most widely prescribed medication in the world. ‘People using these antacids have low stomach acid levels, which allows bacteria usually living in the mouth or consumed to enter the intestine. As a result, the microbiome composition changes and appears to become less favourable. Therefore, people using these antacids may suffer from intestinal bacterial inflammation, for instance.’
Weersma suspects that in the Netherlands, approximately two million people are using these antacids, some of which have been prescribed. ‘These medicines are highly effective and are used to treat various conditions such as gastric ulcers and heartburn. However, doctors should be less eager to prescribe such medicines for people with abdominal complaints for which they are not specifically intended. In addition, it is even more important to taper people off these medicines in time. Even when they are not indicated anymore, their use is frequently continued.’
Effects on immunotherapy
Much research is being done on the microbiome, both here and internationally. A research project conducted at the UMCG has shown that the microbiome has a direct impact on glucose metabolism and the risk of developing diabetes mellitus. ‘An international study recently published in a scientific journal has shown a connection between intestinal flora and immunotherapy in cancer patients. Apparently, the effects of immunotherapy on a tumour, such as skin cancer, depend on the intestinal flora’, Weersma says.
Technical developments enable us to determine the function of all different types of bacteria. Weersma explains: ‘Previously, a Petri dish was used to culture one bacterium. Nowadays, DNA sequencing allows us to analyse all faecal DNA and to determine the hundreds of various bacteria in faeces and, therefore, the intestine.’
‘As a result, the microbiome can be studied in its capacity as an ecosystem as well as for its role in certain diseases. For the last five to ten years, we have paid more attention to this subject and have gained a great deal of knowledge. For instance, we now know that the intestinal flora of healthy people varies considerably from that of people with a chronic bowel disease such as Crohn’s disease or ulcerative colitis. The latter group has far fewer bacteria considered to support proper functioning of the digestive system, for instance by producing short-chain fatty acids, and more pathogenic bacteria.’
Nowadays, it is also possible to change intestinal flora composition, for instance by the transfer of stool from a healthy donor. Weersma says: ‘Leiden University has a Dutch Donor Faeces Bank. Dutch research has shown that faecal transplantation in patients with an intestinal infection caused by Clostridium difficile is highly effective. This infection causes diarrhoea and poses problems particularly in care institutions, because the people living there have low immunity. This infection is difficult to cure with antibiotics, but a single infusion of stool from a healthy donor proves to be a good remedy. In the Netherlands, a study has begun into the effects of faecal transplantation in people with ulcerative colitis, a chronic bowel disease. The UMCG is among the participating research teams of the study.’
‘We are also conducting studies on how microbiome composition in people with Crohn’s disease changes over time and on the role of, for instance, nutrition and other factors. People with this disease collect a faecal sample on a weekly basis for one year. As Crohn’s disease is a chronic illness with flare-ups, we intend to examine whether the microbiome shows changes during such flare-ups.’
More research focusing on the intestine
In 2018, together with researchers from other Dutch university medical centers, researchers at the UMCG received a Gravitation grant of almost 19 million euros. This funding allows them to study organs on chips for the next 10 years. The researchers at the UMCG are focusing on an intestine-on-chip, i.e. a miniature version of an intestine.