NEW FINDINGS have revealed a specialised sub-set of cells residing in the gut as being important regulators of intestinal inflammation through a body clock mechanism, serving as important evidence towards the long-observed link between irregular sleep patterns and gut health. The work came from a group of researchers from the Champalimaud Centre for the Unknown, Lisbon, Portugal.
Regular sleep-wake patterns have been associated with lower risks of obesity and high blood pressure, and accordingly those who work for long periods of time at night are at higher risk of different pathologies, including various gastrointestinal conditions. “To understand why this happens, we started by asking whether immune cells in the gut are influenced by the circadian clock,” commented group leader Dr Henrique Veiga-Fernandes.
Using a mouse model subject to 24-hour clock disruption, the researchers found that group 3 innate lymphoid cells (ILC3) were particularly susceptible to changes in clock gene function. “Surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome, and altered lipid metabolism,” explained Veiga-Fernandes.
Through clock gene disruption, ILC3 number was dramatically reduced in the gut, accompanied by severe inflammation, gut barrier breaching, and fat accumulation. Further investigation showed that this reduction in cell number was due to disruption to the mice brains’ circadian circuit, preventing a vital signal from reaching the ILC3 clock genes. Signal absence prevents a further important protein from directing transient ICL3 to migrate to the gut to carry out important immune functions.
The group hypothesised that, during daylight feeding times, our bodies have evolved in a way so as to direct ICL3 away from the gut through circadian influence, a means to boost lipid metabolism; however, ICL3 absence can predispose the gut to damage. The neuro-immune axis shifts to direct ICL3 to return to the gut in night-time conditions, repairing damage sustained during the day. This repair is thus inhibited when circadian cycles are irregular.
These exciting findings go some way to explaining how people who lead nocturnal lives are predisposed to poorer gut health compared with the general populace.
