Time-restricted feeding prevents depressive-like behaviors by suppressing changes in the gut microbiota

Long-term high-fat diet (HFD) intake changes the gut microbiota to an inflammatory state, which induces inflammation in the brain and is related to the onset of metabolic abnormalities and depression. Time-restricted feeding (TRF) has been shown to inhibit HFD-induced weight gain and gut inflammation. However, the effects of TRF on HFD-induced depression are not fully understood. In this study, we investigated the effects of TRF on depression induced by a HFD. The mice were divided into three groups as follows, and subjected to an 8-week intervention; normal diet (NC), a HFD ad libitum (FA), and TRF with a HFD (FT). The results revealed significant weight gain and depressive-like behaviors in the FA group compared with the NC group, but not in the FT group. Immunohistological analysis in the brain revealed a significant increase in the number of activated microglia and neural cells in the FA group compared with the NC group, whereas these were lower in the FT group. Serum leptin levels were significantly greater in the FA group than in the NC group, whereas these were lower in the FT group. Furthermore, fecal analysis revealed a significant decrease in gut microbiota diversity and increase in bacteria associated with depression in the FA group compared with those in the NC group, whereas these were lower in the FT group. Our study suggests that HFD intake induces inflammatory changes in the gut microbiota and inflammation of the brain, leading to obesity and depression, and that these changes may be prevented by TRF.