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Paper of the Month

Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition

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

Nature. 2018 Aug 8. doi: 10.1038/s41586-018-0395-5. [Epub ahead of print], Druck am 23.8. 2018

Vollständiger Artikel: https://www.nature.com/articles/s41586-018-0395-5externer Link

Foto: Marcus Fulde, Prof. Dr. vet. med., Institut für Mikrobiologie und Tierseuchen, Fachbereich Veterinärmedizin, FU Berlin

Marcus Fulde (Erstautor)

Kommentar: In dieser Arbeit wurde ein Mechanismus identifiziert, der die Kolonisierung von kommensalen Bakterien im Darm bei neugeborenen Mäusen steuert. Die Anwesenheit flagellierter Bakterien führt dabei über die Erkennung durch den Toll-like Rezeptor 5 (TLR5) zur Stimulation einer lokalen antimikrobiellen Antwort, die diese Kolonisierung unterdrückt und damit die Zusammensetzung der neonatalen Darmflora steuert. Interessanterweise bleibt die Zusammensetzung der einmal etablierten Darmflora erhalten, obwohl die epitheliale  Expression on TLR5 auf die Zeit kurz nach Geburt beschränkt ist.

Abstract:

The neonate is born sterile. After birth. exposure to bacteria during passage of the birth canal  and contact to the mother’s skin and environmental sources rapidly leads to colonization of the neonate’s body surfaces. Bacterial numbers rise rapidly but a diverse and stable microbiota only develops over time. Notably, this early enteric microbiota was thought to be mainly determined by exogenous exposure since the neonate’s intestine provides plenty nutrients and space for bacteria to grow. Marcus Fulde in this article was able to show that the host actively shapes the composition of enteric microbiota during the postnatal period. Using a neonatal mouse model, he demonstrates that the postnatal enteric epithelium (but not the epithelium of adult mice) expresses high levels of the flagellin receptor Toll like receptor (TLR)5, which able to induce a local antimicrobial response. Administration of a 1:1 mixture of flagellated and non-flagellated bacteria led to a selection and predominant colonization by non-flagellated bacteria in neonate but not adult or Tlr5 deficient mice. Likewise, germ-free neonate mice but not adult or Tlr5 deficient neonate mice when given the “dysbiotic” microbiota of a Tlr5 deficient mice  were able to partially “correct” for the “dysbiosis”. In these animals, the transferred TLR5 microbiota became more similar to a wild-type microbiota over time. Surprisingly, this change in the microbiota persisted although intestinal epithelial Tlr5 expression was restricted to the immediate postnatal period. Together, these results demonstrate that the neonate host actively selects the bacteria that form the enteric microbiota. They also explain why the postnatal period represents a particularly important time window for the formation of a healthy enteric microbiota.

Letztauthor/Corresponding author:

Mathias Hornef, Prof. Dr. med., Institut für Medizinische Mikrobiologie, RWTH Universitätsklinikum, Pauwelsstr. 30, 52074 Aachen. E-Mail: mhornef@ukaachen.de