Far infrared radiation (FIR) has been widely used to treat chronic diseases and symptoms; however, the underlying mechanism remains unclear. As gut microbiota (GM) markedly impact the host’s physiology, making GM a potential target for the therapeutic evaluation of FIR. C57BL/6J mice were exposed to five times of 2 min-FIR exposure on the abdomen, with a two-hour interval of each exposure within one day. Fecal samples were collected on day one and day 25 after the FIR/control treatment, and the extracted fecal DNAs were evaluated using ERIC-PCR and 16S amplicon sequencing. Host’s G-protein coupled receptors (GPCR) were analyzed using qRT-PCR. FIR induced immediate changes in the GM composition. A prompt and significant (p | Far infrared radiation induces changes in gut microbiota and activates GPCRs in mice