Understanding the functional relevance of microbiome signatures

Dirk Haller

Technische Universität München, München, Germany

Research of the past decade identified a fundamental role of the intestinal microbiome in the regulation of human health, and the disruption of microbiome-host symbiosis contributes to the initiation and progression of various acute and chronic disorders, such as infections, inflammatory bowel diseases, graft-versus-host diseases, cancer and metabolic diseases. All of these pathologies correlate with changes in the intestinal microbiome, and first clinical trials support the hypothesis that patients benefit from microbiome therapy. Nevertheless, and despite enormous efforts in cataloguing aberrant microbiome alterations, the functional specificity and the clinical relevance of dysbiosis is not well understood. One reason for this knowledge gap is an insufficient understanding to the cause-and-effect relationship of microbiome-host interactions in disease. Microbiome signatures are suggested to be unique configurations of microbial communities and their function capable of stratifying disease risk and progression. Here, I will illustrate the effect size of microbiome interventions at early life stages and diseased conditions applying randomized controlled trials. In addition, the challenging question how to identify a cause-and-effect relationship between microbiome changes and host functions will be addressed using ex vivo chemostat cultures and gnotobiotic studies in disease-relevant animal models.

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