The gut microbiome is the totality of microorganisms, bacteria, viruses, protozoa, and fungi within the gastrointestinal tract. The gut microbiome plays key roles in various physiological and pathological processes through regulating varieties of metabolic factors such as short-chain fatty acids, bile acids and amino acids. Nuclear receptors, as metabolic mediators, act as a series of intermediates between the microbiome and the host and help the microbiome regulate diverse processes in the host. Recently, nuclear receptors such as farnesoid X receptor, peroxisome proliferator-activated receptors, aryl hydrocarbon receptor and vitamin D receptor have been identified as key regulators of the microbiome-host crosstalk. These nuclear receptors regulate metabolic processes, immune activity, autophagy, non-alcoholic and alcoholic fatty liver disease, inflammatory bowel disease, cancer, obesity, and type-2 diabetes.

In this review, we have summarized the functions of the nuclear receptors in the gut microbiome-host axis in different physiological and pathological conditions, indicating that the nuclear receptors may be the good targets for treatment of different diseases through the crosstalk with the gut microbiome.