Another rich source of information with the potential to contain pertinent disease risk factor data is the human microbiome – the collective genome of trillions of microbes, including bacteria, viruses, fungi, and parasites that reside in the human gastrointestinal tract. The microbiome contains 100-fold more genes than the human genome, and is considered a bona-fide ‘second genome’ with fundamental roles in multiple aspects of human physiology and health, including obesity, non-alcoholic fatty liver disease, inflammatory diseases, cancer, metabolic diseases, cardiovascular disease, aging, and neurodegenerative disorders. As such, it should capture different aspects of disease than existing risk factors, and their combination can lead to earlier and more robust disease detection. However, very few microbiome-based markers predictive of disease onset and progression were found to date and none are currently used by healthcare systems. Thus, discovery of microbiome-based risk factors is a promising yet mostly unexplored research area.