ABSTRACT: It is well known that host-microbes and immunity interactions are influenced by dietary patterns, as well as daily environmental light-dark (LD) cycles that entrain circadian rhythms in the host. Emerging data has highlighted the importance of diet patterns and timing on the interaction among circadian rhythms, gut microbiome, and immunity, however, their impacts on LD cycles are less reported. Therefore, we aim to study how LD cycles regulate the homeostatic crosstalk between gut microbiome, hypothalamic and hepatic circadian clock oscillations and immunity. We hypothesized that different environmental LD cycles: (1) constant darkness, LD0/24; (2) short light, LD8/16; (3) normal LD cycle, LD12/12; (4) long light, LD16/8; and (5) constant light, LD24/0, may affect immunity and metabolism to varying degrees. Therefore, 240 mice were managed with chow diets (CD) and antibiotics treatments (ABX) under five different LD cycles for 42 days. The liver (LIV), hypothalamus (HYP), inguinal white adipose tissue (iWAT), ileum epithelium (ILE), colon epithelium (COL), jejunum epithelium (JEJ), cecum epithelium (CEC), spleen (SPL), mammary gland (MAG), and thymus gland (THY) tissues were obtained for studying their impacts immunity using RNA-Seq data.