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

Nov 7, 2025Journal of agricultural and food chemistry

Fructo-oligosaccharides may help fix daily changes in thinking disrupted by a high-fat diet in mice through the gut-brain connection

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Abstract

Prebiotic fructo-oligosaccharides (FOS) restored cognitive function and neuroplasticity gene activity in high-fat diet-induced obese mice.

Cognitive deficits were assessed using the Barnes maze and novel object recognition tests.
FOS improved diurnal oscillations of neuroplasticity genes and reduced levels of neuroinflammatory markers (TNFα, IL-6, IL-1β).
FOS altered gut microbiota dynamics and enhanced intestinal barrier integrity.
The treatment normalized diurnal patterns of microbial metabolites, particularly short-chain fatty acids (SCFAs).
This suggests a potential dietary strategy targeting gut microbiota to address cognitive and metabolic disruptions.

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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 (,,) 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 diurnalexpression), 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. Bdnf Psd95Ngf Occludin

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

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