Benefits
Mood and depressive symptom scores in healthy adults
In two placebo-controlled trials of 4 billion live cells a day for 6 weeks, in 33 students and in 70 healthy adults, depression inventory scores did not differ from placebo at any time point, although they fell within the probiotic groups. In the larger trial a separate analysis by sex found lower scores in men only. Probiotical supported both trials.
Anxiety scores in healthy adults
In 70 healthy adults, state anxiety was lower than on placebo after 6 weeks (p = 0.04) but not at the other four time points. Trait anxiety and a depression sensitivity score were already lower in the probiotic group at the start, and the sensitivity score showed no difference once baseline was taken into account. A 6 week trial in 33 students found no difference from placebo.
Mood, anxiety and stress scores in adults with mild low mood
In 39 adults with mild depressive symptoms confirmed by a psychologist, one capsule a day for 12 weeks gave no difference from placebo on any depression, anxiety, stress or quality of life score; depressive symptom severity was the main end point. Scores fell in both groups. The Australian licensee of the blend and a university funded it, with a Probiotical author.
Self-rated sleep quality
In 33 students, sleep quality ratings improved within the probiotic group over 6 weeks but did not differ from placebo. In 70 healthy adults, time to fall asleep, sleep disturbance and the overall sleep quality score improved with the probiotic, though the abstract gives no comparison with placebo, and a wrist tracker found no change in sleep time or awakenings.
Inflammation, cortisol and blood sugar markers
These are blood and saliva markers, not felt outcomes. In 39 adults with mild low mood, C-reactive protein and the morning cortisol rise were lower than on placebo at 12 weeks and, in an exploratory analysis, fasting glucose fell more. In 70 healthy adults, cortisol and C-reactive protein did not differ from placebo over 6 weeks.
Mechanism of action
Gut microbiota changes
In the student trial, gut bacteria profiles shifted on both the probiotic and the maltodextrin placebo. L. rhamnosus and L. fermentum were detected in the probiotic group, and the placebo itself raised bifidobacteria. How people responded depended on their starting gut bacteria type.
Serotonin and GABA in the blood
In 70 healthy adults, plasma serotonin rose within the probiotic group, but the change over time did not differ from placebo and did not track changes in mood or anxiety scores. In 39 adults with mild low mood, serotonin rose in both groups at 6 weeks and GABA did not change. Blood levels do not show what happens in the brain.
Gut barrier and endotoxin markers
In the 12 week trial in adults with mild low mood, blood markers linked to bacterial endotoxin exposure (LPS-binding protein and soluble CD14) fell more than on placebo, while short-chain fatty acids in the blood were largely unchanged. These are marker results from one small trial.
Urine and blood metabolite profiles
In 21 healthy adults given 4 or 40 billion live cells a day for 8 weeks, urine and serum metabolite profiles changed during supplementation, with some differences by dose. The study had no placebo group and measured no health outcome.
Clinical trials
Randomized, double-blind, placebo-controlled parallel trial; one 2.5 g sachet a day with 4 billion CFU of LF16, LR06, LP01 and B. longum 04 or a maltodextrin placebo for 6 weeks, then a 3 week washout; registered NCT03539263 in 2018, after the trial ended in 2017, with Probiotical S.p.A. as sponsor and the product listed as Bifihappy; Probiotical supported the study and supplied the product and placebo; three authors were employed by BIOLAB s.r.l. of Novara, listed as Probiotical Research in later papers; a companion paper by Calgaro and colleagues analyzed gut bacteria; main report (Marotta et al. 2019, Front Psychiatry)
38 healthy university volunteers aged 19 to 33 were randomized; 33 completed (18 probiotic, 15 placebo) after 5 dropped out because they needed antibiotics.
The primary outcome, the Leiden Index of Depression Sensitivity, showed no difference in total score; only the acceptance subscale differed at week 6 (p = 0.031). Beck Depression Inventory scores did not change in either group and did not differ between groups. Mood state depression, anger and fatigue scores and sleep quality improved within the probiotic group, but the paper reports no between-group differences.
Randomized, double-blind, placebo-controlled parallel trial; one capsule a day with 1 billion live cells of each strain (4 billion total) or maltodextrin for 6 weeks, then a 3 week washout; registered NCT05343533 in March 2022, after the trial ended in January 2022, with seven primary questionnaires; co-sponsored by Probiotical S.p.A. and Ashland; one author works for Probiotical and one is a scientific advisor to Ashland; a corrigendum restated the dose as live cells; sleep results appear in a second paper by Kerksick and colleagues, which Europe PMC lists as funded by Probiotical; main report (Walden et al. 2023, Front Nutr)
70 healthy men and women aged 18 to 50 (35 men, 35 women) who completed the study.
Beck Depression Inventory scores did not differ from placebo at any of five time points; a sex analysis found lower scores in men only. State anxiety was lower than placebo at week 6 (p = 0.04). Trait anxiety and depression sensitivity were lower in the probiotic group from baseline, and baseline-adjusted sensitivity changes did not differ. Cortisol, C-reactive protein, dopamine and serotonin showed no group by time interaction. Sleep quality scores improved with the probiotic, with no placebo comparison in the abstract, and wrist tracker sleep did not change.
Randomized, double-blind, placebo-controlled trial; one capsule a day with 1 billion live cells of each strain or a matching placebo for 12 weeks; primary end point depressive symptom severity, sized on the Beck Depression Inventory; registered ACTRN12621000675820; funded by Biome Australia Trading Pty Ltd, which supplied the capsules and whose product name for the blend is Biome Lift, and La Trobe University; one author is employed by Probiotical Research; two later papers from the same trial report blood markers, one funded by Probiotical SpA with two Probiotical Research authors; main report (Moschonis et al. 2026, Br J Nutr)
39 adults in Melbourne with subthreshold depression confirmed by a psychologist interview (19 probiotic, 20 placebo); 30 completed 12 weeks; intention-to-treat analysis.
No between-group difference or treatment by time effect on any depression, anxiety, stress or quality of life score; Beck Depression Inventory scores fell in both groups. Compared with placebo, C-reactive protein and the cortisol awakening response were lower at 12 weeks and glutathione higher at 6 weeks. Later analyses found serotonin rose in both groups at 6 weeks, GABA did not change, and fasting glucose fell more than on placebo (-1.8 versus 0.1 mmol/L, p = 0.036) in an exploratory analysis in which glucose values varied widely between people. One probiotic participant withdrew with reflux and nausea.
Two-dose study without a placebo group; after a baseline phase, volunteers were randomly assigned to 4 billion or 40 billion CFU a day of the four strains for 8 weeks; registered NCT04506385 with Probiotical S.p.A. as sponsor; four authors are at Probiotical Research, and the authors declared no competing financial interest (Di Cesare et al. 2023, J Proteome Res)
21 healthy adults aged 24 to 64 (15 women, 6 men); 11 on the lower dose and 10 on the higher dose.
Urine and serum metabolite profiles measured by NMR changed during supplementation, with some differences by dose. No mood, stress, sleep or other health outcome was measured, and without a placebo group the changes cannot be separated from the passage of time.