Peripheral sex differences in serum serotonin modulation in habitual short sleepers: an exploratory randomized trial of encapsulated Lacticaseibacillus rhamnosus GG.

Sleep restriction, serotonin biology, and gut-brain signaling are interconnected, but whether habitual short sleep is associated with altered peripheral serotonin in healthy adults remains unclear. Probiotic modulation of circulating serotonin has also been insufficiently characterized. In this exploratory randomized, double-blind, placebo-controlled study, 21 healthy adults received microencapsulated Lacticaseibacillus rhamnosus GG or placebo for 28 days and were classified by habitual sleep duration as short sleepers (≤5 h/night) or adequate sleepers (≥6 h/night). Fasting serum serotonin was measured at baseline and day 28. Habitual short sleep was not associated with elevated serum serotonin. Female sex was associated with higher adjusted day-28 serum 5-HT in the primary winsorized log-transformed ANCOVA model (Type II ANOVA: F = 6.04, p = .03, partial η2 = 0.29), whereas treatment and sleep group did not show evidence of association. Although no statistically detectable independent probiotic effect was identified in this small exploratory sample. Directional decreases were observed in some participants with higher baseline serotonin values. These findings suggest that sex may be an important source of variation in peripheral serotonin and support further adequately powered studies using objective sleep phenotyping and prespecified sex-stratified analyses.