Oligosaccharide and Flavanoid Mediated Prebiotic Interventions to Treat Gut Dysbiosis Associated Cognitive Decline

Abstract

Oligosaccharides are potential prebiotic which maintains gut microbiota and improves gut health. The association of gut and brain is named as gut-brain-axis. Gut dysbiosis disrupts gut-brain-axis and effectively contributes to psychiatric disorders. In the present study, Xylo-oligosaccharide (XOS) and Quercetin were used as therapeutic interventions against gut dysbiosis mediated cognitive decline. Gut dysbiosis was established in mice through administration of Ampicillin Sodium, orally for 14 days. XOS and quercetin were administered separately or in combination along with antibiotic. Gene expression studies using mice faecal samples showed both XOS and quercetin could revive Lactobacillus, Bifidobacterium, Firmicutes and Clostridium which were reduced due to antibiotic treatment. FITC-dextran concentration in serum revealed XOS and quercetin protected intestinal barrier integrity against antibiotic associated damage. This was verified by histopathological studies showing restored intestinal architecture. Moreover, intestinal inflammation which increased after antibiotic treated animals was reduced upon XOS and quercetin treatment. Behavioural studies demonstrated that gut dysbiosis reduced fear conditioning, spatial and recognition memory which were reversed upon XOS and quercetin treatment. XOS and quercetin also reduced inflammation and acetylcholine esterase which were heightened in antibiotic treated animal brain. They also reduced oxidative stress, pro-inflammatory cytokines and chemokines and protected hippocampal neurons. In conclusion, XOS and quercetin effectively reduced antibiotic associated gut dysbiosis and prevented gut dysbiosis associated cognitive decline in mice.

Keywords: Antibiotic; Cognition; Gut dysbiosis; Gut-brain axis; Prebiotics; Quercetin.