Education > Article > Probiotics in Human Clinical Trials | Research

Probiotics in Human Clinical Trials | Research

In 2001, the World Health Organisation published a report indicating the health benefits of probiotic supplements. In 2005, the first paper was published that proposed the use of probiotics as an adjunctive treatment for major depressive disorder. Since then, the research field has steadily grown and indicates that the gut microbiota probably plays a crucial part in the pathophysiology of depression, as well as conditions related to mucosal barrier impairment and inflammation. Our probiotic partners, Winclove, have collaborated with research partners to increase the research in the gut-brain-barrier field. Ecologic® Barrier (Bio.Me™ Barrier) has been published in several human clinical trials, which are summarised below.

Vulnerability to Depression (1)

A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood

Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. This study aimed to test if a multi-species probiotic (Ecologic® Barrier / Bio.Me™ Barrier) may reduce cognitive reactivity in non-depressed individuals.

Twenty healthy participants without a current mood disorder received a 4-week probiotic, while 20 control participants received an inert placebo in this triple-blind, placebo-controlled, randomised, pre and post-intervention assessment.

In the pre- and post-intervention assessment, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale. Compared to participants who received the placebo intervention, participants who received the 4-week multi-species probiotics showed a significantly reduced overall cognitive reactivity to sad mood (p<0.001), which was largely accounted for by reduced rumination (p<0.001) and aggressive thoughts (p<0.01).

These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood.

Working Memory Under Stress (2)

Randomized controlled trial on the effect of probiotics on neurocognition

In a double blind, randomised, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested once before and once after a 28-day intervention with 2g/d Ecologic® Barrier (Bio.Me™ Barrier).

Without stress induction, probiotics did not affect brain, behavioural, or related self-report measures. However, relative to placebo, the probiotics group did show a significant stress-related increase in working memory performance after supplementation (p=0.039). This change was associated with intervention-related neural changes in the frontal cortex during cognitive control exclusively in the probiotics group.

These results show neurocognitive effects of a multi-species probiotic in healthy women only under challenging situations, buffering against the detrimental effects of stress on cognition.

Liver Cirrhosis (3)

Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis

In a randomised, double blind, placebo-controlled study, stable cirrhotic out-patients either received a daily dose of a probiotic powder (Ecologic® Barrier / Bio.Me™ Barrier) (n = 44) or a placebo (n = 36) for 6 months and were followed up for another 6 months.

A significant but subclinical increase in neutrophil resting burst (2.6–3.2%, p=0.0134) and neopterin levels (7.7–8.4 nmol/L, p=0.001) was found in the probiotic group, but not with placebo. Probiotic supplementation did not have a significant influence on neutrophil phagocytosis, endotoxin load, gut permeability or inflammatory markers.

Probiotic supplementation significantly increased serum neopterin levels and the production of reactive oxygen species by neutrophils. These findings might explain the beneficial effects of probiotics on immune function. Furthermore, probiotic supplementation may be a well-tolerated method to maintain or even improve liver function in stable cirrhosis. However, its influence on gut barrier function and bacterial translocation in cirrhotic patients is minimal.

Migraine (4)

Migraine prophylaxis with a probiotic

In an uncontrolled observational study of patients whose headache had been classified as migraine (n=1,020; 11.8% male, 88.2% female), 3g probiotics (Ecologic® Barrier / Bio.Me™ Barrier) were given twice daily for 8 weeks.

After 8 weeks of probiotic use, the mean number of days of migraine attacks was reduced by 33% to 1.38 days (p≤0.001). The intensity of the migraines reduced (p≤0.001), and furthermore, the intensity of accompanying symptoms (e.g. nausea, vomiting, photosensitivity, etc.) was reduced by an average of >70% in all symptoms (p<0.001).

Probiotic supplementation had an overall positive effect, and reduced the need for intake of analgesics (p≤0.001); however, further randomised, placebo-controlled studies are required.


  1. Steenbergen, L., et al. (2015). A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain, Behaviour, and Immunity. Aug;48:258-64. doi: 10.1016/j.bbi.2015.04.003
  2. Papalini, S., et al. (2019). Stress matters: Randomized controlled trial on the effect of probiotics on neurocognition. Neurobiology of stress doi:
  3. Horvath, A., et al. (2016). Randomised clinical trial: the effects of a multispecies probiotic vs. placebo on innate immune function, bacterial translocation and gut permeability in patients with cirrhosis. Alimentary Pharmacology and Therapeutics. Nov;44(9):926-935. doi: 10.1111/apt.13788
  4. Straube, V, A., et al. (2018). Migraine prophylaxis with a probiotic. MMW-Fortschritte der Medizin. 160 (S5):16-21

Related Articles

Bio.Clear, Bio.Me, GI Microbiome, Immunology & Inflammation
Optimising Your Immune System

To help optimise immunity, it is imperative that we nourish the immune system from the outside-in and inside-out with an emphasis on nurturing our relationship with the microbial colonies with ...

Bio.Me, Immunology & Inflammation
Medicinal Mushroom Formula

Bio.Revive™ Mycommune is a synergistic blend of medicinal mushrooms containing over 100 biologically active compounds providing well-rounded support for immunity and biologic function.

HMOs as Prebiotics to Reinforce Innate Immune System

Galactooligosaccharides (GOS) is one of our key supplements to promote a healthy microbiome for immune health and host-microbiome homeostasis.