Gut feelings: Can we optimize lifestyle, diet and medication according to our respective microbiota?

Despite our best efforts of finding the perfect regimen of diet, exercise and medication to keep any person fit and healthy, outcomes for different people vary widely for all of these measures, even when we comply with them fully. Some of this traces to our individual genetics, which remains difficult to change, but another source of variation in responses may come from differences between our gut microbiomes. Human bodies are not sterile, and our skin, our mucosal surfaces and, in particular, our intestines are home to many more bacteria than there are human cells in our bodies, representing hundreds of different species in each person. These microbial ecosystems, or microbiomes, are found in all animals and have coevolved with their hosts. Therefore we rely on commensal ("friendly") bacteria for many functions, including breaking down nutrients, converting some medications into their active forms, producing certain crucial compounds for us from our diet, and helping our immune systems mature and remain tuned. The microbiota also contains temporary visitors and both transient and resident opportunistic pathogens, often kept in check by the immune system and by the commensals, but sometimes escaping such control to multiply and cause disease. Human gut microbiomes begin establishing at birth and evolve over a lifetime, but remain quite stable within each person throughout adulthood unless something serious like repeated antibiotic cures disrupt them. However, they can differ quite substantially between individuals as well as between populations, reflecting factors such as nutrition and environmental exposures. It has been proposed, and to a degree already demonstrated, that differences between individuals in which gut bacteria they harbour may underlie differences in their susceptibility to disease, their resilience to stressors, and their responses to environmental stimuli. Thus the variation in responses to the same lifestyle between different people may reflect their gut microbiomes. This would open up several venues of personalized medicine, lifestyle advice and nutrition. Choice of medications, diets or interventions could be selected according to a person's specific microbiome to be most effective. It might also be possible to potentiate such interventions by altering the gut microbiome in different ways, such as through antibiotics, probiotics, nutrition or through microbiome transplantation from another person. Alternately put, by adapting the microbiome to a lifestyle intervention, and/or adapting a lifestyle intervention to the microbiome, we may be able to optimize how a given person can seek and achieve fitness and health. In this talk, I will outline what we know on these topics so far, especially from studies using large-scale microbial (meta-)genome DNA sequencing. In this talk I will draw on work by my own lab at the Charité in Berlin, as well as that of our colleagues, rivals and collaborators elsewhere in the world. I will give examples of known gut microbial modulation of human responses to the external environment and introduce the most common strategies both for researching such effects and for their leverage as health-promoting tools. Where there are limits to our knowledge or obstacles to its practical application, I will identify those obstacles and suggest ways to overcome them.