Heat-Treated Limosilactobacillus fermentum PS150 Improves Sleep Quality with Severity-Dependent Benefits: A Randomized, Placebo-Controlled Trial.

No significant group × time interactions were detected for the primary outcomes PSQI and ISI in the full cohort.

• Both the HT-PS150 and placebo groups showed improvements in PSQI and ISI over time.
• The trial enrolled 84 adults aged 20–60 years with PSQI ≥ 5 and ISI < 22.
• The intervention duration was eight weeks in a randomized, double-blind, placebo-controlled design.
• Per-protocol analyses required ≥80% compliance.

A higher proportion of participants in the HT-PS150 group exhibited up-regulated nocturnal melatonin secretion compared with placebo.

• This finding came from an exploratory proportional regulation analysis that classified individual biomarker changes as up- or down-regulated.
• Proportions of participants with up-regulated nocturnal melatonin were compared between study arms.
• Melatonin was measured from urine, saliva, and/or blood samples.
• This was an exploratory, not a pre-specified primary, analysis.

A higher proportion of HT-PS150 participants showed improved daytime plasma orexin levels compared with placebo.

• Orexin was among the sleep-relevant biomarkers measured from urine, saliva, and/or blood samples.
• The finding was detected in exploratory proportional regulation analyses.
• This was interpreted as evidence of stabilizing wakefulness signaling.

HT-PS150 was associated with a tendency toward greater reductions in nocturnal salivary cortisol compared with placebo.

• This finding was observed in exploratory proportional analyses.
• Nocturnal salivary cortisol was used as a marker of HPA-axis activity.
• The reduction was described as a 'tendency,' indicating it did not reach formal statistical significance.
• Cortisol was among the biomarkers measured alongside melatonin, orexin, serotonin, GABA, and norepinephrine.

In subgroup analyses restricted to participants with higher baseline insomnia severity (ISI ≥ 8), HT-PS150 was associated with greater improvements in PSQI, notably sleep duration and efficiency, and greater reductions in anxiety (GAD-7).

• These findings were from post hoc subgroup analyses and were not pre-specified primary analyses.
• The subgroup was defined by a baseline ISI score of ≥ 8.
• Improvements were specifically noted in the PSQI subcomponents of sleep duration and sleep efficiency.
• Anxiety reduction was measured by the GAD-7 scale.
• The authors suggest potential utility of HT-PS150 in more symptomatic populations based on these results.

The trial assessed a broad set of outcomes including patient-reported sleep quality, anxiety, depression, quality of life, gastrointestinal symptoms, wrist actigraphy, and multiple endocrine/circadian biomarkers.

• Patient-reported outcomes included PSQI, ISI, GAD-7, PHQ-9, QLESQ-SF, and VAS-GI.
• Objective sleep was measured via wrist actigraphy using Fitbit Inspire 3 devices.
• Biomarkers included melatonin, cortisol, orexin, serotonin, GABA, and norepinephrine measured from urine, saliva, and/or blood.
• Repeated measures were analyzed using generalized estimating equations.

The study was motivated by preclinical evidence for Limosilactobacillus fermentum PS150 and the proposed role of the microbiota-gut-brain axis in melatonin and HPA regulation.

• The intervention used a heat-treated formulation of L. fermentum PS150 (HT-PS150), distinguishing it from live probiotic preparations.
• Insomnia was characterized as prevalent and difficult to treat safely over the long term.
• The gut-brain axis mechanism was proposed to involve modulation of melatonin and hypothalamic-pituitary-adrenal (HPA) pathways.