The microbiome of dental pockets plays a central role in periodontitis

HZI researchers elucidate new mechanisms related to periodontitis

28.09.2015

The sample was obtained from the dental pocket and then subjected to Illumina Sequencing (top, middle). Below this you see a treponema, one of the most dangerous pathogens in the dental pocket. The…

@HZI/Wagner-Döbler

Periodontitis is one of the most common infectious diseases in the world. Approximately ten percent of all humans are affected by the disease and this number rises to fifty percent in the elderly. Periodontitis is triggered by a Biofilm in the dental pockets that consists of several hundred different types of bacteria. The ways, in which these bacteria cooperate, have recently been researched by scientists from the Helmholtz Centre for Infection Research (HZI) in Braunschweig who analysed approximately ten million active genes from dental pockets. Their results are published in the new open-access Nature Online journal, "Biofilms and Microbiomes".

In its final stage, periodontitis leads to tooth loss and also increases the risk of heart attack, rheumatism, miscarriage, autoimmune diseases and other systemic diseases. To understand exactly how periodontitis arises, is necessary to exactly analyse the activity of the biofilm causing the disease. "These microorganisms include both well-studied Pathogens and others that have thus far been considered to be just ancillary and harmless flora," says Prof Irene Wagner-Döbler, who is the director of the "Microbial Communication" research group at the HZI. She and her colleagues performed what is called a metatranscription analysis.

Rather than sequencing the genome itself, i.e. the DNA, the messenger RNA, i.e. working copies of the genes, and this means all active genes of all types of bacteria of the periodontal pocket, are sequenced in this method. These approximately ten million active teens are subsequently analysed by method of bioinformatics. "It was essential that we compared the gene expression in bacterial populations from humans with periodontitis to those of healthy subjects," says Wagner-Döbler.

This allowed the scientists to demonstrates that a typical dweller of dental pockets, the Prevotella nigrescens bacterium changes its role depending on whether or not periodontitis is manifest. "As soon as periodontitis is manifest, the usually harmless P. nigrescens turns into a so-called "accessory pathogen" and attacks the Host much in the same way as already known pathogens," says Wagner-Döbler. This exacerbates the disease and makes it more difficult to control. "While it was previously presumed that one only needs to eliminate the main pathogens of the Infection to prevail over the disease, our results indicate that this will not be sufficient," says Wagner-Döbler.

Another new insight concerns the role of the oral bacterium, Fusobacterium nucleatum, which is common in dental pockets. It was presumed that F. nucleatum produces toxic butyric acid in an inflamed dental pocket and thus contribute to the periodontitis. However, the analysis of the gene expression showed that F. nucleatum always produces butyric acid, in healthy and ill individuals. However, in ill people a number of other types of bacteria also contribute to the production of butyrate and this type of bacterium also uses other biochemical pathways for this purpose. "Our results indicate that this important process also involves a whole range of bacteria not previously known to be related to this process," says Wagner-Döbler.

In addition, the scientists succeeded to identify biomarkers for periodontitis. Biomarkers are characteristic biological features that can be measured objectively and are indicative of a normal or disease process in the body. "We found three genes that regularly showed particularly high gene expression in patients afflicted with periodontitis," says Wagner-Döbler. These three biomarkers could now be validated in a large patient cohort and might in the end allow periodontitis to be diagnosed at an early stage such that therapy can become much more successful. As a result, the researchers contributed to a basic new understanding of a polymicrobial biofilm disease and made a significant step towards early diagnosis.

 

Original publication:

Szymon P Szafrański , Zhi-Luo Deng, Jürgen Tomasch, Michael Jarek, Sabin Bhuju, Christa Meisinger, Jan Kühnisch , Helena Sztajer, Irene Wagner-Döbler. Functional biomarkers for chronic periodontitis and insights into the roles of Prevotella nigrescens and Fusobacterium nucleatum; a metatranscriptome Analysis.  and Microbiomes. 2015 Sep 23. 1:15017. DOI:10.1038/npjbiofilms.2015.17