Parappilly_2025_Sci.Rep__

Gut microbiota plays a pivotal role in maintaining human health and well-being. Antibiotic-induced dysbiosis disrupts microbial balance and diversity leading to compromised physiological functions and adverse health outcomes. The present study investigates the functional potential of a dietary fiber-based hybrid-hydrogel microparticles formulation of the naturally occurring dietary flavonoid, quercetin (FQ-35), as a prebiotic intervention to restore gut and brain health through modulation of microbiome-gut-brain axis. An antibiotic cocktail was administered to induce gut microbial imbalance, and subsequently assessed the effects of supplementation of FQ-35 (100 mg/kg b.wt, for 14 days) on cognitive performance, gut microbiota, markers of gut and brain integrity, along with histopathological changes. FQ-35 effectively restored gut microbial diversity, demonstrated by a significant enrichment of beneficial taxa such as Lactobacillus and Bacteroides, alongside the normalization of key gut integrity markers, including ZO-1 and Occludin. Behavioural studies further demonstrated the improvement in memory and restoration of acetylcholinesterase activity, which were impaired by antibiotic cocktail. The intervention also led to the downregulation of pro-inflammatory mediators such as TLR4, TNF-alpha, and IL-1beta. These findings highlight the therapeutic/functional potential of FQ-35 in restoring homeostasis via. the gut-brain axis, indicating its plausible role in the mitigation of dysbiosis.