Small Intestinal Microbiota Oscillations, Host Effects and Regulation—A Zoom into Three Key Effector Molecules

SIMPLE SUMMARY: The gut microbiota and its secreted molecules feature a daily rhythm that interacts with the host and influences its function in health and disease. Immune-related molecules are involved in the daily interaction between the microbiota and the host and can be influenced by diet, including fasting and feeding cycles. In this review, we delve into the specific impacts of Reg3γ, IgA, and MHCII to showcase the varied effects of the gut microbiota's daily activity on the host. We also discuss current challenges, remaining questions, and perspectives in understanding the relationship between the microbiome and circadian rhythms. ABSTRACT: The gut microbiota features a unique diurnal rhythmicity which contributes to modulation of host physiology and homeostasis. The composition and activity of the microbiota and its secreted molecules influence the intestinal milieu and neighboring organs, such as the liver. Multiple immune-related molecules have been linked to the diurnal microbiota-host interaction, including Reg3γ, IgA, and MHCII, which are secreted or expressed on the gut surface and directly interact with intestinal bacteria. These molecules are also strongly influenced by dietary patterns, such as high-fat diet and time-restricted feeding, which are already known to modulate microbial rhythms and peripheral clocks. Herein, we use Reg3γ, IgA, and MHCII as test cases to highlight the divergent effects mediated by the diurnal activity of the gut microbiota and their downstream host effects. We further highlight current challenges and conflicts, remaining questions, and perspectives toward a holistic understanding of the microbiome’s impacts on circadian human behavior.