The microbiome is part of a complex ecosystem of the human body. The skin is not only influenced by commensal microbes that colonize the skin, but it is also affected by the gastrointestinal microbiome. An interactive relationship and communication between the gastrointestinal tract, skin and immune system is called the gut-skin axis. This interplay is mediated through inflammatory mediators, metabolites and the intestinal or skin barrier. The human microbiome functions also as a regulator of the innate and adaptive immune system with a profound impact on the host homeostasis. The gut and skin microbiome composition and diversity is influenced by the host exposome throughout life, including but not limited to the route of delivery, diet, climate and many other factors. A dysbiosis of the microbiome can therefore have significant consequences for the development of diseases affecting the skin and or the intestines. The skin–gut axis is an area of emerging research. Gaining a deeper understanding of the bidirectional relationship between the gut and skin microbiome will reveal the role of an altered microbiome in gastrointestinal and/or skin pathologies. We may unlock novel therapeutic approaches for managing diseases by restoring a healthy microbiome and improve well-being and quality of life.