How is our gut flora affected when our immune system is compromised during illness? This is the question a team of researchers at Rigshospitalet, University of Copenhagen, would now like to answer by analysing 1,200 faecal samples.
The biological samples lie, side by side, in small plastic tubes with airtight lids in the freezer at the Persimune research centre at Rigshospitalet in Copenhagen.
This is where researchers are working to help groups of patients whose immune systems are compromised due to a variety of diseases and who are therefore at particularly high risk of catching life-threatening infections.
In some cases, patients’ immune systems are suppressed because they have undergone an organ transplant. They may, for instance, have received a donor kidney which means that they will have to take immunosuppressive drugs for the rest of their lives to prevent rejection of the foreign organ. In other cases, the patient’s immune system may have taken a beating during cancer therapies such as chemotherapy or a bone marrow transplant.
One of the ways in which researchers can study the effects of a compromised immune system is to map the patient’s gut flora, using faecal samples. It is biological samples of this kind that Persimune has in its freezer – around 1,200 in total. Emma Elizabeth Ilett, doctor and Lundbeck Foundation-funded PhD student at Persimune, explains that these samples, taken from around 750 immunocompromised patients with a variety of different illnesses, will now be used in a high-calibre study:
‘Our overriding research question is “what happens to the gut bacteria – that is, how is the gut flora affected – when a person’s immune system comes under pressure”? We want to examine this across a range of the diseases we deal with here at Persimune; for instance, to find out whether the changes to gut flora we see when the immune system is compromised are common to all of the diseases and therefore can be considered to be more general in nature.’
A gigantic factory
Human gut flora, the human microbiome, is currently one of medical science’s high-profile research fields. This is, in particular, due to the development of new tools for DNA analysis.
These tools have given us a glimpse of the incredible complexity of the human microbiome, which in reality is a kind of gigantic factory: a biological system found in each and every human being, made up of billions of bacteria, weighing around a kilo in total and typically representing many hundreds of species. In addition to metabolising our food, it looks as though these gut bacteria could be involved in numerous pathogenic processes, from depression and dementia to obesity. And, on the positive side, it is thought that the bacteria could provide protection against a number of diseases.
One of the issues the researchers at Persimune would like to investigate by analysing and comparing the numerous faecal samples concerns bone marrow transplants. Emma Elizabeth Ilett explains:
‘When we perform a bone marrow transplant, for instance to treat certain types of leukaemia, we have to suppress the patient’s own immune system before he or she can receive the donor cells. This is a fairly simple procedure for some patients, and these patients may benefit from a bone marrow transplant. However, other patients experience serious complications when undergoing both immunosuppression and the treatment itself. We don’t actually know why this is, but we have a suspicion that the gut flora may play some role here. This is one of the questions we’ll be looking at in more detail.’
Emma Elizabeth Ilett also believes that the data collected by the researchers at Persimune could have an impact on faecal transplants in the long term. This therapy involves transferring gut bacteria from a healthy donor to a patient – to optimise the recipient’s gut flora.
The method is being considered – and is to some extent being tested – for chronic intestinal diseases. However, doctors are still reluctant to use faecal transplants because there is a lack of clarity about the scope and type of characteristics that are transferred.
Faecal samples should preferably be appropriately packaged and put into a freezer without delay, as soon as the biological material has been collected. This is the best way to store the sample until it is analysed. A technique known as ‘fresh-frozen’ (FF) is used for this on-the-spot collection.
In some cases, collecting samples this way can pose practical difficulties, for instance if the person giving the sample is physically impaired.
The question is whether a method other than FF could be used in such situations, of course without resulting in decomposition of the material and loss of informational value.
A study recently published in the scientific journal Scientific Reports indicates that this is actually possible. In collaboration with Spanish and German colleagues, the researchers at Persimune are the people behind this study, which is funded by the Danish National Research Foundation and the Lundbeck Foundation, among others.
‘We demonstrate that the material can be preserved in a special fluid instead of being stored in a freezer. This makes it easier to take faecal samples from very sick patients. And patients who live at home and are receiving therapy as an outpatient would also be able to help doctors collect samples,’ says Emma Elizabeth Ilett, first author of the scientific article.