The human gut microbiome, diet, and health: “Post hoc non ergo propter hoc”

•Documented causative links between alterations of the microbiome and health range from very strong to very weak.•Elucidating the mechanisms behind host-diet-microbiota interactions is a prerequisite for targeting the microbiome therapeutically.•Machine learning algorithms allow us to leverage structured biological knowledge in high-dimensional metagenomic data analysis.

The gastro-intestinal microbiome has become the subject of intensive research, which is beginning to elucidate its roles in human health. It is becoming increasingly recognised that gut microbiota plays a part in regulating human immune homeostasis and metabolism, which gives rise to novel opportunities for preventative and treatment strategies. The key challenge in this field is the ability to define causality in the relationship between nutrition, microbiota and host health. In this commentary we argue for an increased focus on cause-and-effect relationships within studies that relate to the human microbiome in health and predispositions to disease. With the right experimental models, data accessibility infrastructure and advanced machine learning tools, causal relationships among components of complex host-microbiome systems can be elucidated.