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Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
Studies by the Cluster of Excellence PMI and the DFG Research Unit “miTarget” are investigating the function of the intestinal microbiome during pregnancy and breastfeeding and its potential significance for patients with chronic inflammatory bowel disease.
Pregnancy is accompanied by profound changes in the body. Among other things, these affect the energy metabolism and the immune system. But the gut microbiome, i.e. the composition of the microbial community in the gut, also changes considerably, especially towards the end of pregnancy. “We are interested in how these microbiome changes influence the course of disease in patients with chronic inflammatory bowel disease (IBD),” explained Professor Philip Rosenstiel, member of the Board of Directors of the Cluster of Excellence ‘Precision Medicine in Chronic Inflammation’ (PMI) and Director of the Institute of Clinical Molecular Biology (IKMB) at the Faculty of Medicine at Kiel University (CAU) and the University Medical Center Schleswig-Holstein (UKSH). Although it is known that the intestinal flora is linked to the development of IBD, it is unclear whether individual changes during pregnancy are related to the course of the disease before and after delivery. A research team from the Cluster of Excellence PMI investigated this question in an animal model for the chronic inflammatory bowel disease Crohn's disease. The results were recently published in the journal Gut Microbes.
More inflammation in the gut, smaller offspring
“We looked at what effect a single genetic risk factor for Crohn's disease had on the microbiome of pregnant animals,” explains study leader Rosenstiel. By switching off the Crohn's risk gene Atg16l1 in cells of the intestinal mucosa, the condition of Crohn's disease was simulated in the mice. The composition and metabolic activity of the intestinal microbiome was examined at various times during pregnancy and lactation and the results were compared with thoase of mice without gene modification. “At the beginning of pregnancy, the microbiome of animals with and without genetic defects was very similar. Over time, however, the composition of the microbiome drifted apart between the groups. This shows us that a genetic risk factor in a very specific cell type is sufficient to influence these changes, which develop over time. Interestingly, the animals that had the Crohn's risk factor showed more signs of inflammation and the offspring had a lower weight.”
Chemical analyses of the metabolic products showed that the altered composition of the microbial community also results in different metabolic activity. “The observed changes are linked to pro-inflammatory processes. This means that the altered microbiome could play a part in the observed tendency towards inflammation,” says Rosenstiel. These results are not directly transferable to the situation in humans. “But it is important to understand how genetic IBD risk factors can affect pregnancy. Then you know what to look out for in the microbiome, for example.” The long-term goal is to use the microbiome changes for diagnostic purposes, for example to predict or possibly even treat a flare-up of the disease after pregnancy.
Analysis of the course of the disease and pregnancy in women with and without IBD
How pregnant women with and without chronic inflammatory bowel disease are doing, what symptoms they have and how they cope with everyday life is also the subject of the observational study “MamaIBD” at the Center of Excellence for Inflammation Medicine at the UKSH, Kiel Campus. For this purpose, clinical data as well as blood and stool samples are collected in each trimester of pregnancy, and symptoms and everyday activities are recorded using questionnaires. In women with IBD, disease activity is also recorded. “We want to find out how chronic inflammatory bowel disease affects the everyday activity and symptoms of pregnant women,” explains assistant doctor Martina Guggeis, who is supervising the project as a clinician scientist. The biosamples collected will be used for further scientific analysis, for example to determine how genetic risk factors and environmental influences in women with and without IBD lead to the inflammatory activity of the intestinal microbiome occurring or not. Rosenstiel: “We analyze the gut microbiome and look at what the gut microbiome of a woman who has an IBD flare-up after pregnancy looks like compared to a woman without a flare-up. It may be possible to use these differences as microbial biomarkers to predict a flare-up and adapt the therapy to the individual.”
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The composition of the intestinal microbiome changes during pregnancy. The influence of genetic risk factors for chronic inflammatory bowel diseases is being investigated by studies of the PMI Cluster of Excellence.
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Professor Philip Rosenstiel, Director at the Institute of Clinical Molecular Biology, CAU and UKSH, and board member of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI).
© Tebke Böschen/University of Kiel
About the Cluster of Excellence PMI
The Cluster of Excellence "Precision Medicine in Chronic Inflammation" (PMI) is being funded from 2019 to 2025 through the German Excellence Strategy (ExStra). It succeeds the "Inflammation at Interfaces” Cluster, which was already funded in two periods of the Excellence Initiative (2007-2018). Around 300 members from eight institutions at four locations are involved: Kiel (Kiel University, University Medical Center Schleswig-Holstein (UKSH), Muthesius University of Fine Arts and Design, Kiel Institute for the World Economy (IfW), Leibniz Institute for Science and Mathematics Education (IPN)), Lübeck (University of Lübeck, University Medical Center Schleswig-Holstein (UKSH)), Plön (Max Planck Institute for Evolutionary Biology) and Borstel (Research Center Borstel - Leibniz Lung Center).
The goal is to translate interdisciplinary research findings on chronic inflammatory diseases of barrier organs to healthcare more intensively, as well as to fulfil previously unsatisfied needs of the patients. Three points are important in the context of successful treatment, and are therefore at the heart of PMI research: the early detection of chronic inflammatory diseases, the prediction of disease progression and complications, and the prediction of individual responses to treatment.
Cluster of Excellence "Precision Medicine in Chronic Inflammation"
Scientific Office
Christian-Albrechts-Platz 4, 24118 Kiel, Germany
Contact: Sonja Petermann
+49 (0)431 880-4850
spetermann@uv.uni-kiel.de
Press contact:
Frederike Buhse
Public Relations, Excellence Cluster PMI
+49 (0)431/880 4682
fbuhse@uv.uni-kiel.de
https://www.precisionmedicine.de/en/
Link:
https://www.precisionmedicine.de/en/genetic-risk-factor-for-crohns-disease-influ...
Prof. Dr. Philip Rosenstiel
Faculty of Medicine, CAU
Institute for Clinical Molecular Biology, CAU Kiel, UKSH
Phone: 0431/500-15105
p.rosenstiel@mucosa.de
López-Agudelo VA, Falk-Paulsen M, Bharti R, et al. Defective Atg16l1 in intestinal epithelial cells links to altered fecal microbiota and metabolic shifts during pregnancy in mice. Gut Microbes. 2024 Jan-Dec;16(1):2429267. https://doi.org/10.1080/19490976.2024.2429267
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