MEAL TIMING MODULATES COGNITIVE FUNCTION AND CIRCADIAN NEUROBIOLOGY VIA THE GUT MICROBIOTA: HUMAN EVIDENCE AND TRANSLATIONAL FINDINGS IN MURINE MODELS

Scientific evidence suggests that the timing of food intake, beyond caloric content, can influence brain function through interactions with circadian physiology and the gut microbiota. To explore this neurobiological implication of time-restricted eating (TRE), we examined whether early (eTRE; 08:00–16:00) versus late (lTRE; 14:00–22:00) eating patterns produce distinct cognitive and emotional outcomes, and whether microbiota-dependent mechanisms mediate these effects. Thirty-four adults with obesity followed eTRE or lTRE within a structured hypocaloric intervention. Although both regimens yielded similar anthropometric and metabolic improvements, lTRE was consistently associated with a more efficient response in controlling cognitive interference.
To determine whether microbial communities causally contribute to these neurobehavioral differences, fecal samples from each condition were transplanted into microbiota-depleted mice. Remarkably, mice receiving lTRE-derived microbiota exhibited better long-term memory performance, reduced anxiety-like behavior, and increased hypothalamic expression of the circadian genes Bmal1 and Clock, analyzed by RT-qPCR, suggesting more robust central circadian alignment. Microbiota profiling using QIIME2, DADA2, and ANCOM-BC, revealed that lTRE donors had higher abundances of bacterial genera associated with neuromodulatory metabolites (e.g., Lactobacillus, Oscillibacter, Phascolarctobacterium), potentially linking meal timing, microbial activity, and brain function.
Together, these findings indicate that the temporal structure of feeding can modulate cognition and circadian neurobiology via microbiota-dependent pathways, highlighting meal timing as a modifiable factor of the gut–brain axis.