Microbiome research in Graz

In the last decades, the human microbiome has gained momentum in the scientific community and developed into an exciting new research field. The microbiome is the genetic material of all microbes – bacteria, fungi, viruses, archea, and also protozoa– that live in and on the human body. The microbiome is essential for human development, immunity and nutrition, therefore it comes as no surprise that it is the focus of international research efforts. Graz, the capital of the Austrian province Styria, has engaged in the microbiome research early on and today it is recognized as an established microbiome research location. Modern microbiome research in Graz started around 15 years ago, when next generation sequencing technologies became available at a reasonable cost. The Medical University of Graz (Medizinische Universität Graz), the Graz University of Technology (TU Graz) and the Karl Franzens University (KF Graz) quickly invested in state of the art equipment and fostered a swift increase in essential expertise and know-how. In excellent collaborations between microbiome and clinical research facilities, flawlessly characterized samples and profound knowledge on bioinformatics and advanced biostatistics built the foundation for innovative research.

Colonies of typical gut bacteria on blood agar, incubated in anaerobic (i.e. oxygenfree) conditions. Although not all gut bacteria can be cultivated in laboratory set-ups, isolated cultures are essential for research on the gut-liver axis.

Microbiome and the gut-liver axis

A particular research focus has been placed on the gut–liver axis. Because of its anatomical and physiological proximity, the gut (including the microbiome) and the liver are in constant communication with each other. One essential aspect of this relationship is to protect the body from bacteria and bacterial products translocating through the gut barrier. The liver acts as a firewall in this scenario, simultaneously filtering harmful substances/bacteria from the blood while keeping inflammatory immune responses and resulting tissue damage in check. If the gut-liver axis is disturbed, chronic diseases such as liver cirrhosis can develop. When scientists in Graz began to study the microbiome, cirrhosis was one of the initial starting points – however, the gut-liver axis also plays an important role in other diseases such as dementia, diabetes and metabolic syndrome. Current studies also explore the interference of certain drugs with the gut-liver axis. The effect of long-term proton pump inhibitor (PPI) use on the gut-liver axis is a prominent research focus in Graz. PPI can cause oralization of the intestinal microbiome, which means that oral bacteria colonize the intestine. These oral bacteria are associated with intestinal inflammation and gut barrier dysfunction, which is especially troublesome for patients with liver cirrhosis or other chronical diseases. In fact, the presence of particular oral bacteria can be used to predict liver-related deaths in cirrhotic PPI users. The most probable pathophysiological link between PPI use and oralization is the reduction of acid production in the stomach and the resulting increase in survival of oral and food-borne microorganisms. In a proof-of-concept study, this link could very recently be confirmed: patients after distal gastrectomy who have a reduced gastric acid production after the surgery also showed remarkably similar alteration in the gut microbiome and comparable levels of intestinal inflammation as patients with long-term PPI use.

Measurement of transepithelial electrical resistance can be used to study gut permeability in-vitro. Either tissue samples or cell-line monolayers can serve as a gut barrier model and deliver mechanistic insights in microbiome/gut and liver research.

Impact of Covid-19 on microbiome research

While Covid-19 certainly had consequences for ongoing studies, the pandemic and the resulting public health measures also encouraged out-of-the-box thinking. While, on the one hand, scientists raced towards therapeutic and immunization strategies, on the other hand, new ways to conduct clinical studies – and protect participants and investigators in the process – were in dire need. In cooperation with CBmed, researches from the Medical University of Graz will launch a tele-medical pilot study to test the effects of a probiotic intervention on COVID19-associated diarrhoea. This study is designed as a randomized, double-blind, placebo-controlled trial where the investigators and the participants communicate exclusively online or over the phone. After an initial video call, the patients receive a package in the mail that contains all the necessary information, sample tubes and their study medication, which is either a probiotic or a placebo. The participants will collect stool in special virus-deactivating sampling tubes and send them back to the research facility for in-depth analysis. This enables the patients to participate in clinical studies while in home quarantine, and the researcher can collect otherwise unapproachable information about the disease. If successful, the study will serve as an example how clinical studies can be conducted in infectious settings, and possibly set the corner stone to more inclusive research for patients from remote areas, with reduced mobility or immune deficiencies in the future.

The Authors