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Deciphering the molecular language orchestrating host-microbiome interactions and their effects on health and disease

Final Report Summary - META-BIOME (Deciphering the molecular language orchestrating host-microbiome interactions and their effects on health and disease)

The mammalian intestine contains trillions of microbes, a community that is dominated by members of the domain Bacteria but also includes members of Archaea, Eukarya, and viruses. The vast repertoire of this microbiome functions in ways that benefit the host. The mucosal immune system co-evolves with the microbiota beginning at birth, acquiring the capacity to tolerate components of the community while maintaining the capacity to respond to invading pathogens. The gut microbiota is shaped and regulated by multiple factors including our genomic composition, the local intestinal niche and multiple environmental factors including our nutritional repertoire and bio-geographical location. Moreover, it has been recently highlighted that dysregulation of these genetic or environmental factors leads to aberrant host-microbiome interactions, ultimately predisposing to pathologies ranging from chronic inflammation, obesity, the metabolic syndrome and even cancer. In this ERC-funded project, we have identified various possible mechanisms participating in the reciprocal regulation between the host and the intestinal microbial ecosystem, and demonstrate that disruption of these factors, in mice and humans, lead to dysbiosis and susceptibility to common multi-factorial disease. Understanding the molecular basis of host-microbiome interactions may lead to development of new microbiome-targeting treatments. In short, we have discovered host and microbial factors cross-regulating the cross talk between these two parts of the human body, and identified components of the molecular language dictating host-microbiome interactions that dictate metabolic and immune health or the propensity to develop common 'multi-factorial' diseases such as obesity, diabetes, fatty liver, and inflammatory bowel disease. Most importantly, we've uncovered new principles of probiotic, prebiotic, and postbiotic interventions aimed at correcting aberrant host-microbiome interactions in these disorders.