Herrenhausen Conference: "Beyond the Intestinal Microbiome – From Signatures to Therapy"
Experts from fields as diverse as Inflammation, Microbial Communication, Evolutionary Game Theory, and Diabetes gathered in Hanover to address open questions as well as to discuss the multiple new insights and opportunities for research trying to unriddle the mysteries of the gut microbiome.
Our Conference Topics at a Glance
- Molecules of Communication
- Intestinal Ecology and Environmental Influences
- Development and Primary Colonization
- Function of the Meta-organism
- Microbiome and the Brain – Role of the Gut-Brain Axis
- Inflammation and Autoimmunity
- Diabetes and other Metabolic Diseases
- Therapeutical Approaches
Karsten Kristiansen, University of Copenhagen and BGI-Shenzhen
The importance of the gut microbiota for regulation of metabolism and immune functions is well established, and evidence has been presented that the gut microbiota may also affect behavior. However, the exact molecular mechanisms by which bacteria in the gut exert their actions still remain elusive. Our laboratory is involved in large-scale metagenomics projects in collaboration with BGI-Shenzhen, using high throughput Illumina-based sequencing of total fecal DNA. These studies have primarily been focused on humans and mice, but have now been extended to encompass several other species including pigs and fish. In this lecture I will first summarize our data on the mouse, the pig, and the human gut microbiota, pointing to differences and similarities. In large scale studies of human cohorts we have recently described changes in the gut microbiota that characterize obese individuals, individuals with type 2 diabetes, and patients suffering from colorectal cancer revealing characteristic changes in the diversity and functional competences of the gut microbiota. I will conclude the lecture by discussing possible functional consequences and perspectives of these findings.
Arne Traulsen, Max Planck Institute for Evolutionary Biology
Evolutionary game theory provides a powerful way to think about interactions between different phenotypes. This mathematical approach allows us to make very general statements about the stability of communities, and is particularly powerful for analyzing the interplay of competition and cooperation and the emergence of polymorphisms. Can this theory be applied to microbial communities in the gut? A combination of simple models and experimental data shows that some general statements about the dynamics in such communities can be made, but a bottom up approach based on transparent mathematical models requires a different view on the data, and in some cases laborious experiments.
Charles R. Mackay, Monash University
Human disease is affected by diet, as well as by the composition of the gut microbiota, through poorly understood mechanisms. One of the major activities of commensal microbes is digestion of dietary fibre to yield short chain fatty acids (SCFAs). Deficiency of dietary fibre, in particular, has been associated with increased mortality due to various diseases. Decreasing amounts of fibre intake in western countries is one hypothesis for the increased incidences of certain inflammatory diseases. SCFAs affect numerous biological systems, either through stimulation of ‘metabolite-sensing’ G-protein coupled receptors or through inhibition of histone deacetylases (HDACs). We found that diets deficient in fibre produced marked alterations in the composition of the gut microbiota in mice, and led to exacerbated disease in models of intestinal injury and inflammation, colon cancer, type 1 diabetes, asthma, and wound healing. In contrast, very high intake of dietary fibre protected against these conditions. The burring questions in the field of dietary metabolites to be addressed in future studies are: What is the relative importance of metabolite-sensing GPCRs versus HDACs for gut health and human disease? How important are metabolites such as SCFAs for a ‘developmental origin’ of disease, i.e. diseases that are put in train in utero or during breast feeding, and which may have an epigenetic basis? What are all the metabolites of beneficial bacteria, and are non-bacterially produced metabolites important as well?
Harald Renz, University of Marburg
Overwhelming evidence indicates a strong impact of environmental microbes on the programming and the development of (early) immune responses. Based on clinical and epidemiological data, a certain exposure of environmental microbes – particularly of bacteria – seems to be an important pre-requisite for programming immune responses towards the tolerance default program. Such programming on the level of the adaptive immune responses is necessary, and required in order to prevent unwanted (chronic) inflammatory diseases and many autoimmune diseases. The grand challenge is to define the appropriate microbial environment on the cellular and molecular level in order to delineate the underlying mechanism of microbe-host interaction. Microbial diversity is one important finding the scientific community largely agrees upon. Conversely, reduced diversity is closely linked to several clinical phenotypes that precede the clinical onset of the disease, suggesting a cause-effect relationship. This concept implies the loss of evolutionary co-evolved microbial strains and is the result of changes in lifestyle condition. The great challenge is to delineate the molecular pathomechanism of gene-environment interactions and the impact of microbial communities on this complex and intimate relationship. Therefore, it is urgently needed to move this research field towards translational activities.