Abstract
Circadian disruption, e.g. through shift work, causes microbial dysbiosis and increases the risk of
metabolic diseases. Microbial rhythmicity in mice depends on a functional intestinal clock and
frequent jetlag as well as high-caloric energy intake induces loss of these oscillations. Similarly,
arrhythmic microbiota was found in obese and T2D populations. However, the interplay between
the intestinal circadian clock, the microbiome, diet and host metabolism is poorly understood.
In intestinal-specific Bmal1 knockout mice (Bmal1IEC-/-
) we demonstrate the relevance of the
intestinal clock in microbiome oscillations and host and microbial nutrient metabolism. Microbiota
transfer from Bmal1IEC-/- mice into germ-free recipients led to obesity, reflected by increased
bodyweight and fat mass. Western diet-fed Bmal1IEC-/- mice increased bodyweight likely through
mechanisms involving the intestinal clock-control of lipid and hexose transporters. Additionally, we
identified dietary fiber as novel link between circadian microbial rhythmicity, intestinal clock
functioning and host physiology. Thus, revealing the potential of fiber-rich diet intervention as a
non-invasive strategy targeting microbial oscillations in metabolic disease prevention.