An international study with the participation of the Cluster of Excellence "Inflammation at Interfaces" has for the first time demonstrated a factor which is only active for a brief period after birth, yet has life-long consequences.
You can't teach an old dog new tricks. This saying seems to not only apply to learning in general, but also to essential biological processes. After birth, there is a particularly important time window, in which the bacterial community in the gut, the so-called microbiome, is formed. In the study published in the journal Nature, a molecular factor was identified, which is only active in mice until 21 days after birth, and during this time influences which bacteria colonise the intestines. "One can't relate this 100% to the situation in humans, but for the mouse this is about the time when the transition occurs from mother's milk to solid food. In humans this would equate to approximately 6 months," said second author Dr Felix Sommer, from the working group of cluster Board Member Professor Philipp Rosenstiel at the Institute of Clinical Molecular Biology at Kiel University and the Collaborative Research Centre 1182 “Origin and Functions of Metaorganisms”.
Previous experiments already indicated that there is a time window for determining the composition of the microbiome. The results now published in Nature demonstrate the existence of a specific mechanism innate to the immune system, which is only active for a short time after birth, and regulates the colonisation with microorganisms. This phase is formative for the life-long composition of the microbiome.
The research team under the leadership of the microbiologist Professor Mathias Hornef from the RWTH Aachen investigated the epithelial cells of the intestine of young and older animals for the presence of receptors of the innate immune system, which recognise bacterial structures. Especially with the receptor TLR5 (Toll-like receptor 5), there was a significant age dependency. Three-day-old animals had a significantly higher expression of the receptor than older animals. This observation was the starting point for experiments on the colonisation of germ-free young and old mice with the microbiome of other animals. "TLR5 recognises flagellin, the main component of bacterial flagella. Mice in which TLR5 has been genetically removed, have an altered microbiome due to the spread of flagellated bacteria. We colonised germ-free wild-type mice with the intestinal flora of other animals, some with the bacterial mix from other wild-type mice and some with bacteria from genetically-modified mice without TLR5," explained Sommer, who was responsible for the detailed analysis of the microbiome for the project. "With the young wild-type colonised animals, the microbiome changed over time and in both cases was similar to that of the wild-type animals. They have an active TLR5 receptor and can therefore shape the bacterial composition. Unlike the adult animals, which no longer have the receptor. And that is exactly what was also reflected in the experiment." Conversely, it was shown that with germ-free mice which have been genetically modified to produce no TLR5, neither young nor adult animals could influence the TLR5 microbiome towards that of the wild-type microbiome.
The composition and the balance of intestinal bacteria are essential for health. Various studies have shown that, for example, chronic inflammatory diseases or metabolic diseases are linked to altered intestinal flora. However, it has so far not been possible to significantly influence the microbiome in the long term in adulthood by external factors, such as diet or special treatments. "The microbiome is much more stable than one might expect, given everything it interacts with on a daily basis. Even after a gastrointestinal infection or antibiotic treatment, after some time the individual microbiome reverts to its original composition", emphasised Rosenstiel. "The study shows that there is a critical phase very early in life, in which we need to see certain bacteria, so that thereafter a diverse and well-functioning intestinal microbiome is present."
Marcus Fulde, Felix Sommer, Benoit Chassaing, Kira van Vorst, Aline Dupont, Michael Hensel, Marijana Basic, Robert Klopfleisch, Philip Rosenstiel, André Bleich, Fredrik Bäckhed, Andrew T. Gewirtz, Mathias W. Hornef: Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition. Nature. Published 08 August 2018. doi: 10.1038/s41586-018-0395-5
Dr Felix Sommer
Institute of Clinical Molecular Biology, Kiel University
Tel.: 0431/500- 15146
Prof. Dr Philip Rosenstiel
Institute of Clinical Molecular Biology, Kiel University
Tel.: 0431/500 15111
The Cluster of Excellence "Inflammation at Interfaces" has been funded since 2007 by the Excellence Initiative of the German Government and the federal states with a total budget of 68 million Euros. It is currently in its second phase of funding. Around 300 cluster members are spread across the four locations: Kiel (Kiel University, University Medical Center Schleswig-Holstein (UKSH), Muthesius University), Lübeck (University of Lübeck, UKSH), Plön (Max Planck Institute for Evolutionary Biology) and Borstel (Research Center Borstel (FZB) – Center for Medicine and Biosciences) and are researching an innovative, systematic approach to the phenomenon of inflammation, which can affect all barrier organs such as the intestines, lungs and skin.
Cluster of Excellence "Inflammation at Interfaces"
Head: Dr habil. Susanne Holstein
Christian-Albrechts-Platz 4, 24118 Kiel, Germany
phone: +49 (0)431 880-4850, Fax: +49 (0)431 880-4894
Twitter: I@I @medinflame