Gut microbiota and intestinal mucosal barrier function
In the Schröder lab we are interested to better understand the close relationship between host and microbes in the intestine. Specifically, we focus on antimicrobial peptides, which are host-produced peptide antibiotics, and intestinal mucus, the gel-like layer that is covering the intestinal epithelium. We use a combination of gut microbiota analyses, microbiota transplantations (FMT), state-of-the-art ex vivo mucus measurements, antimicrobial assays, as well as confocal and fluorescence microscopy. In addition, we use dietary interventions in mice and humans and will closely work with Norrlands University Hospital Umeå (NUS) to analyze relevant patient samples.
The mammalian intestine is one of the most densely populated habitats on our planet. Trillions of microorganisms, including bacteria, live in our gut in a relationship from which both sides benefit: The host provides continuous supply of nutrients and a constantly warm temperature, while the bacteria produce vitamins and other factors that are beneficial for the host. However, the high density of the gut bacteria is a permanent threat to the body and efficient defence mechanisms are required to protect the host against infection by his own intestinal bacterial community.
Over the course of evolution, the body has developed various mechanisms of border protection. First, a dense and sticky layer of mucus covers the intestinal surface and thereby physically hinders bacteria from invading into the body. In addition, mucus is filled with so called antimicrobial peptides, which are antibiotics produced by the body to kill bacteria that manage to penetrate into the mucus barrier.
During previous studies in the labs of Fredrik Bäckhed and Gunnar Hansson in Gothenburg, Sweden, we found that mice that were fed a “Western-style diet” – a diet similar to fast food that contains high amounts of simple sugars and fat but lacks dietary fibre – had a different composition of gut bacteria, which caused damages in the mucus shield. Consequently, bacteria could come closer to the epithelium, which increases the risk for infections and inflammation in the gut. Of note, we found that application of a probiotic Bifidobacterium strain or the prebiotic dietary fibre inulin, which is, for example, present in chicory and Jerusalem artichokes, was protective for intestinal barrier function. Thus, bacteria and diet can both affect mucus function, but the details are yet to be determined – one major aim of our research!
Antimicrobial peptides are the second research focus in the lab. These host-produced peptide antibiotics keep bacteria at a distance from the epithelium, but also shape the composition of the gut microbiota. In the laboratory we will study how specific dietary interventions alter antimicrobial peptide expression and function and how this is related to the gut microbiota. Similar to the mucus project, we will use a combination of animal and in vitro studies.
With our research we want to contribute to a better understanding of how modern dietary habits affect intestinal defence mechanisms. In the industrialized world, diseases such as inflammatory bowel disease and metabolic disease are on the rise and have been linked to the gut microbial community and intestinal barrier defects. As diet is one of the most important factors that shapes the community in the gut, we hope to clarify the involvement of specific food components in the complex regulation of gut barrier function. Besides contributing to improved dietary recommendations for the Western society, we hope to identify important bacteria that can be used as future probiotic supplements to improve barrier function in the gut. Moreover, we hope to find nutritional compounds that can enrich these positive bacteria to provide long-term health benefits for the Western gut.