The diurnal rhythm of the cytoprotective human trefoil protein TFF2 is reduced by factors associated with gastric mucosal damage: ageing, Helicobacter pylori infection, and sleep deprivation

OBJECTIVES: To determine if the normal TFF2 diurnal rhythm is disrupted in those with increased risk of gastric morbidity. Trefoil proteins protect the gastrointestinal mucosa from damage and aid its repair. TFF2 is considered the major cytoprotective gastric trefoil protein. There is a marked circadian variation in gastric luminal TFF2 in young healthy volunteers with peak levels present during the night. METHODS: Gastric juice was aspirated at two hourly intervals over a 24-h period via a nasogastric tube. TFF2 was measured by quantitative western transfer analysis. Helicobacter pylori (H. pylori) status was measured by C13 urea breath test and by serology. The effects of H. pylori infection, sleep deprivation, and ageing, which cause increased gastric morbidity, on the TFF2 circadian rhythm were tested. RESULTS: H. pylori infection attenuated the increase in TFF2 that occurs during the night. The TFF2 diurnal rhythm was reduced in older people and both the TFF2 level reached and the time at which the maximum TFF2 concentration occurs were associated inversely with age (p < 0.005). Sleep deprivation delayed the normal night time increase in gastric TFF2 and resulted in an overall reduction in TFF2 secretion. CONCLUSIONS: H. pylori infection, ageing, and sleep deprivation cause a reduction in the TFF2 diurnal rhythm. The demonstration that the TFF2 rhythm is impaired in cohorts of individuals known to suffer gastric symptoms suggests that interventions to restore the normal TFF2 rhythm in those with poor mucosal protection could reduce morbidity.