Cookie Settings

We use cookies to optimize our website. These include cookies that are necessary for the operation of the site, as well as those that are only used for anonymous statistic. You can decide for yourself which categories you want to allow. Further information can be found in our data privacy protection .

Essential

These cookies are necessary to run the core functionalities of this website and cannot be disabled.

Name Webedition CMS
Purpose This cookie is required by the CMS (Content Management System) Webedition for the system to function correctly. Typically, this cookie is deleted when the browser is closed.
Name econda
Purpose Session cookie emos_jcsid for the web analysis software econda. This runs in the “anonymized measurement” mode. There is no personal reference. As soon as the user leaves the site, tracking is ended and all data in the browser are automatically deleted.
Statistics

These cookies help us understand how visitors interact with our website by collecting and analyzing information anonymously. Depending on the tool, one or more cookies are set by the provider.

Name econda
Purpose Statistics
External media

Content from external media platforms is blocked by default. If cookies from external media are accepted, access to this content no longer requires manual consent.

Name YouTube
Purpose Show YouTube content
Name Twitter
Purpose activate Twitter Feeds

Intestinal microbes reprogram genetic activity, thus controlling intestinal development and inflammation

No. 13 | 05/03/2020 | by Koh

Scientists from the German Cancer Research Center and the Hebrew University in Jerusalem demonstrated in mice that intestinal bacteria reprogram DNA activity in cells of the gut mucosa and thus have a considerable impact on the development of the healthy gut. Acute intestinal inflammation induced under experimental conditions led to a huge increase in the activity of inflammation-related and cancer-promoting genes in the mucous membrane cells of microbe-colonized animals.

© Adobe Stock

A large body of research work indicates that the intestinal microbiota – in other words, all the microorganisms that colonize the human gut – and its composition are linked to a whole series of diseases. The illnesses range from inflammatory diseases of the intestine and metabolic disorders such as obesity and diabetes to cancer, autism, and depression.

These studies usually only show links and do not clarify the mechanisms by which the intestinal microbes affect the human body. Frank Lyko from the German Cancer Research Center (DKFZ) and Yehudit Bergman from the Hebrew University in Jerusalem teamed up to address this issue.

To do so, the researchers compared the DNA of the gut mucosal cells in mice with a normal microbiome with those of mice who had grown up in sterile conditions. They focused on analyzing DNA methylation, known as epigenetic marking, which prevents DNA-binding proteins from attaching to the DNA at these sites, hence restricting the activity of the genes there.

The researchers noticed considerable differences in the methylation patterns between sterile and microbe-colonized animals. In the latter, they found a group of "sentinel genes" activated by demethylation, which are responsible for the normal regeneration of the intestinal mucosa in the healthy gut.

Both the microbe-colonized mice and the sterile animals were treated using a chemical that attacks the intestinal mucosa, thus inducing acute inflammation. In the microbe-colonized animals, this treatment led to a reduction in DNA methylation in the gut mucosal cells, particularly affecting a number of regulatory elements. As a result, many genes that play a role in inflammation and in cancer were activated.

In contrast, the chemical hardly caused any changes in genetic activity in the microbe-free mice. "That shows that the differences in methylation are due to the bacteria and not to the chemical," Frank Lyko explained. However, if the microbiome of the microbe-colonized mice was transferred to the microbe-free animals, methylation of the intestinal mucosal cells was reduced in these mice too.

The team of German and Israeli researchers realized that this effect apparently depends on the demethylating enzymes TET2 and TET3: If they were turned off genetically, treatment with the chemical hardly caused any changes in the genome methylation.

"The microbiome seems to have a considerable influence on the animals' health: It ensures normal intestinal development by using epigenetic programming to activate genes that steer regeneration of the gut mucosa. In the microbe-free mice, however, this activation does not take place," Frank Lyko explained. "During acute inflammation, the gut microbes also cause a change in genetic activity, and genes are dysregulated that are also dysregulated in patients with intestinal inflammation and cancer of the colon. This once again underlines the key role that microbes play in epigenetic regulation," he added.

The work was funded by the Helmholtz-Israel Cooperation in Personalized Medicine.

Ihab Ansari, Günter Raddatz, Julian Gutekunst, Meshi Ridnik, Daphne Cohen, Monther Abu-Remaileh, Timur Tuganbaev, Hagit Shapiro, Eli Pikarsky, Eran Elinav, Frank Lyko and Yehudit Bergman: The microbiota programs DNA methylation to control intestinal homeostasis and inflammation.
Nature Microbiology 2020, DOI: https://doi.org/10.1038/s41564-019-0659-3

 

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

RSS-Feed

Subscribe to our RSS-Feed.

to top
powered by webEdition CMS