Fructo-Oligosaccharides Restore High-Fat Diet-Disrupted Diurnal Fluctuations in Cognitive Function in Mice via the Gut-Brain Axis

Diurnal fluctuations in cognitive function serve as a crucial regulatory foundation for maintaining neuroprotective mechanisms and metabolic homeostasis in the brain. High-fat diet (HFD) disrupts these fluctuations, yet nutritional strategies to mitigate this effect remain poorly explored. Here, the current research demonstrated that prebiotic fructo-oligosaccharides (FOS) ameliorated diurnal cognitive deficits (assessed by Barnes maze and novel object recognition tests) and restored hippocampal diurnal oscillations of neuroplasticity genes (<i>Bdnf</i>, <i>Psd95</i>, <i>Ngf</i>) and neuroinflammatory markers (TNFα, IL-6, IL-1β) in HFD-induced obese mice. Furthermore, FOS reshaped gut microbiota diurnal dynamics, enhanced intestinal barrier integrity (reflected in diurnal <i>Occludin</i> expression), and normalized the shifted diurnal patterns of microbial metabolites, particularly short-chain fatty acids (SCFAs). Consequently, FOS reinstated diurnal cognitive plasticity accompanied by normalization of SCFAs and gut-brain axis activity, highlighting a microbiota-targeted dietary approach for diurnal disruption in metabolic disorders.