Immunology

The microbiome in our intestine plays a vital role in people’s health and the immune system Any lack of balance there has not only been linked to chronic inflammatory intestinal inflammation, but also type 2 diabetes and other diseases. A group of researchers at the University Hospital Tübingen has now reported for the first time that they have discovered a mechanism on how the body’s own endogenous antimicrobial defense shield regulates the microbiome and its bacterial composition; the article is publish in a recent edition of the Proceedings of the National Academy of Sciences.

New treatments

This mechanism provides a fundamental understanding of the structure of the intestinal barrier and host microbial interaction. “It throws open the door for future approaches to new treatments, but also for developing antibiotics and beneficial microbiome modulation;” says the head of the working group; Professor Dr. med. Jan Wehkamp from University Hospital Tübingen.

The researchers discover a new “cluster bomb” like effect create by the body’s own antibiotics, the so-called defensins (peptides), which are form and secret in the Paneth granule cells, in the small intestine. “The HD-5 defensin, which the body produces naturally and releases in the intestine, splinters into fragments if it is expos to bacteria in the gastrointestinal wall in certain circumstances.

Different fragments

These fragments do not, however; consist of ineffective waste; as was thought in the past, but they have an antimicrobial effect against commensal; harmless bacteria and bacteria that are pathogenic;” says Prof. Wehkamp; describing the discovery. The researchers have found 250 new antibiotic combinations in all in the different fragments, when examining them in a laboratory. “This mechanism dramatically increases the antimicrobial spectrum against possible intruders,” Wehkamp adds.

The working group in Tübingen, which has been conducting research into the microbiome for many years; was already able to publish an article in in 2011 indicating that defensins play an important role in maintaining the balance between bacteria and the body surfaces in all organisms; particularly in the intestine.

Controlling microbes

The scientists use the latest publication in PNAS to demonstrate how the prevailing conditions inside our intestines affect the activity and structure of the peptides: In reduced conditions with only limited oxygen a situation that often occurs in the intestine  the HD-5 peptide; which is originally secreted in a folded  form; is open and activat.
It becomes more prone to degrading through its new linear structure: As a result; the proteases occurring in the intestinal mucus layer can break up the HD-5 defensin; into many fragments  so activating this antimicrobial weapon. Out of one peptide the body creates endless combinations of attacking and controlling microbes which is a very smart and efficient way of defense.