Probiotics reverse gut dysbiosis and memory impairment associated with esomeprazole use in chronically stressed rats: A significant neuroprotective role for cholecystokinin.

Recent studies propose an association between the prolonged usage of gastric acid suppressants (GAS) and the incidence of dementia in stressed patients. This association was confirmed in our investigation recently published with a significant role for gut dysbiosis using different GAS, especially PPI esomeprazole (Esom). Hence, this work explored the influence of different probiotics on gut dysbiosis associated with Esom use in unpredictable chronic mild stress (UCMS)-induced cognitive impairment. Rats were given Esom (3.7 mg/kg/day orally) with exposure to UCMS for 7 weeks and treated with Lactobacillus delbrukii and Lactobacillus fermentum (LB) (1 × 10 CFU/day orally) or Bacillus clausii (BC) (1 × 10 CFU/day orally) in the last 3 weeks of the experiment. LB and BC attenuated the cognitive impairment associated with Esom use in the presence of UCMS, where BC showed more remarkable results. These results were correlated with improvement of dysbiosis and gut membrane integrity by reducing colonic inflammation via hampering the NLRP3 inflammasome pathway. The improvement of gut dysbiosis was further interrelated with decrease in systemic inflammation and improvement of cholecystokinin (CCK) level. The neuroprotective effects in LB and BC groups were achieved via enhancement of brain-derived neurotrophic factor (BDNF) by 2.7 and 3.4-folds, respectively, through CCK activation with decline of hippocampal amyloid β accumulation by 67.29 % and 97.9 %, respectively, compared to UCMS with Esom group. Our study supports the neuroprotective effect of probiotics on cognitive impairment attributed to long-term use of GAS in the presence of stress, with a significant role for gut microbiota modulation.