Patients with Inflammatory Bowel Disease Show IgG Immune Responses Towards Specific Intestinal Bacterial Genera

The value of research increases when it is shared. That is why at the UMCG we try to make our publications as open as possible by adhering to the principles of open science. This month we focus on open availability of access to biobanks as an important aspect of open science. Our Open Science Publication of June is "Patients With Inflammatory Bowel Disease Show IgG Immune Responses Towards Specific Intestinal Bacterial Genera", by Arno R. Bourgonje, Geesje Roo-Brand, Paola Lisotto, Mehdi Sadaghian Sadabad, Rosanne D. Reitsema, Marcus C. de Goffau (University of Amsterdam and Wellcome Sanger Institute, Cambridge, UK), Klaas Nico Faber, Gerard Dijkstra, and Hermie J. M. Harmsen. This study made use of the String of Pearls and Lifelines biobanks.

Living in harmony with a complex gut bacterial ecosystem

Another reason why this output was selected is because it connects closely to one of the research focal points in the UMCG; studies into the gut microbiome, the collection of microorganisms that live inside us, especially in our digestive system. Arno Bourgonje explains this connection in more detail: “The aim of our study was to gain an understanding of the reactivity of our immune system against the gut microbiome. We did this by comparing samples from patients suffering from Inflammatory Bowel Disease (IBD) with those of healthy volunteers. Often we observe a compromised integrity of the intestinal barrier in patients with IBD. This barrier, however, plays an important role when it comes to digestion, nutrient absorption, and protection against harmful microorganisms. The immune system in the intestinal mucosa plays an important role because it protects us from potentially pathogenic (causing diseae) bacteria, while it also communicates with the remaining parts of our immune system to ascertain that a bunch of  microorganisms beneficial to our health are not recognized as potentially pathogenic since these are important for a healthy gut bacterial ecosystem. Whether certain bacteria are beneficial or detrimental to our health is, however, difficult to determine, since this is usually context-dependent. Determining immune reactivity to this complex gut bacterial ecosystem may give more insight into which of the bacteria cross the intestinal barrier and are being recognized by the immune system as potential intruders. ”

In patients with IBD, the immune system has difficulties separating beneficial and pathogenic  microorganisms, Arno explains. “The intestinal barrier plays an important part in this. The story up to this point is what we already knew. But what we did not know was which type of bacteria are specifically recognized by our immune system. In this study we focused on creating an overall picture of which genera of bacteria are  being recognized in patients versus healthy individuals. This could help us in our search for potential biomarkers of the disease, which could be used to identify patients with IBD in a very early stage. The study could also help us to develop microbiome-targeted therapy for patients, for example by changing nutritional patterns to give the good microorganisms a boost while providing pathogenic bacteria more unfavorable circumstances. So the question which bacteria we need to keep an eye on and may become relevant as therapeutic targets becomes important to answer. What we found was that in this respect the Streptococcus, Lactococcus, and Lactobacillus groups of bacteria were more frequently recognized by the immune system of patients with IBD.

There is an incredible amount of attention for the microbiome in recent days. Geesje Roo-Brand explains why: “Because of technological developments, the gut microbiome is much easier to investigate. With the current technology we can, in a very short amount of time, get the whole microbiome on our display. Fifteen years ago this was very hard to do, regardless of the amount of time it would take you. Handling big data is now also much easier. So there are loads of developments that make studies into the microbiome very interesting. We are learning more and more but it is very complicated and we have a long way to go still. For example, is the microbiome unbalanced as a result of a disease, or was the disease caused by the unbalance? It is akin the chicken or egg story.”

The importance of biobanks

The study performed by Geesje and Arno and their co-authors relied on the availability of stool samples from both patients with IBD and healthy individuals. The biomaterials from the patients with IBD was collected locally, in the UMCG, within the String of Pearls Biobank initiative. For the biomaterials from healthy patients, the study relied on the Lifelines biobank, in which data and samples of 167,000 has been collected and stored. These biobanks enable researchers like Geesje and Arno to compare samples collected from patients with those collected from individuals without any known health issues. But how does that work? Does the researcher just walk out of the biobank with a bag full of jars?

Arno: “Before you are granted access to the samples, the biobank will have to approve your research proposal. Once your proposal is approved, which could take a long time, you get access to the material. Of course the biobank is very restrictive in how much material they hand out, they won’t give you a microliter (one millionth of a liter) more than you need. In this way the biobank does not quickly run out of materials.”

So what is next? In order to apply this new knowledge in a clinical setting, the results will need to be validated. That means a duplication of the study, but with an increased sample size and more integration of clinical and environmental factors. This is necessary to iron out differences in microbiome between the healthy control individuals. Geesje: “These differences can be quite big. If one of the individuals was using medication against heartburn at the time the samples were taken, then this could have serious consequences for the balance of the microbiome.” Arno concludes: “In this way, as a researcher, you’ll run from one study into the next one. But that is inherent to what we do. Repetition and validation are key aspects in this regard.”