Probiotics, Brain Structure and Psychological Variables
Condition: Depressive Symptoms; Anxiety; Stress
MeSH terms: Depression
Study type: Interventional

Summary: 
      Theory and research on the gut-brain-axis emphasize complex interactions between the gut
      microbiota, immunological and hormonal responses, brain function, brain structure, as well as
      resulting behavioral manifestations, such as cognitive functions and mental illness.
      Probiotics are living micro-organisms that change the composition of the gut microbiota and
      hypothetically have a positive effect on the host's general health and well-being. Probiotic
      bacteria naturally occur in foods such as Sauerkraut, olives, and dark chocolate, and are
      currently also added to industrial products such as yogurt.

      Regarding the effect of probiotics on brain structure and function, animal studies have shown
      that the administration of probiotics in mice and rats was linked to neurogenesis in the
      hippocampus and an improvement of associated cognitive functions. The majority of these
      studies applied probiotics for 4 weeks. The substances used in these studies were often
      composed of several bacterial strains, suggesting that the neurogenic effect may not be
      reducible to a specific type of probiotic bacteria.

      Probiotics seem to be effective in improving memory abilities, including spatial and
      non-spatial memory, both in rodents and humans. Moreover, specifically regarding the
      beneficial effect of probiotics on anxiety, depression and stress, preliminary evidence in
      humans is compelling. However methodologically sound (randomized-controlled trial [RCT],
      'blind') studies are still lacking.

      To sum up, the present study is going to be the first RCT with human participants that
      investigates structural and functional changes of the hippocampus through probiotic bacteria,
      using Magnet Resonance Imaging (MRI). In addition, the study aims at advancing research in
      the field by investigating the effects of probiotics on a broad spectrum of cognitive
      functions, particularly those associated with hippocampal activity (e.g. spatial memory,
      verbal memory). Furthermore, effects on several types of mental illness (e.g. anxiety,
      depression, stress) will be studied. Potential translatory mechanisms that may promote the
      aforementioned effects will be examined, i.e. changes in immunological parameters, 'brain
      derived neurotrophic factor' (BDNF), and oxytocin.
    

Detailed description: 
      A double-blind RCT intervention study will be conducted to investigate the effect of a
      probiotic dietary supplement vs. a placebo, taken by healthy human participants (N = 60) for
      28 consecutive days. Both substances are administered in doses of 4.4g (powder) per day.

      The probiotic dietary supplement used in the present study is a freely available product (in
      powder form) sold under the name of Vivomixx®. Per 4.4g the powder contains 450 billion
      bacteria, composed of eight bacterial strains: Lactobacilli (L. paracasei, L. plantarum, L.
      acidophilus and L.delbrueckii subsp. bulgaricus), Bifidobacteria (B. longum, B. infantis, B.
      breve), and Streptococcus thermophiles.

      This product was chosen, because a similar supplement with an identical composition of
      bacteria as Vivomixx® was found to be linked to hippocampal neurogenesis in mice. The placebo
      powder has a similar taste and consistency as the verum (Vivomixx®) powder, but contains no
      probiotic bacteria.

      First, participants will be screened online for eligibility (T0). Before and after the 28-day
      intake period, participants are asked to perform several cognitive tests and fill out
      questionnaires (T1, T2) at our laboratory (ca. 2 - 2.5 hours). Afterwards, blood samples will
      be drawn (ca. 5 minutes) and a magnet resonance tomography (MRT) session (ca. 1 - 1.5 hours)
      will be conducted, where participants will perform an object pattern separation task in the
      scanner (T1, T2). Furthermore, a follow-up after 2 months (T3), including the same
      assessments as at T1 and T2, will be conducted.

      During the intake period participants will fill out a brief questionnaire on a weekly basis,
      which includes an assessment of state depression and anxiety, defecation (control item to
      rule out adverse effects), recent (start of) intake of medication, recent (onset of) intake
      of antibiotics, and recent inter-current illness (e.g. influenza). In addition, participants
      will record their food intake (protocol) for one week (7 consecutive days) during the intake
      period.
    

Intervention name(s): Vivomixx® powder; Placebo powder
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Participants will take in a daily dose of 4.4g for 28 consecutive days; Participants will take in a daily dose of 4.4g for 28 consecutive days
Other intervention name(s): probiotic dietary supplement
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 1 Verum group, receiving the probiotic Vivomixx® powder
1 Placebo group, receiving a placebo powder (similar taste and consistency as Vivomixx® powder)
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Probiotics; Psychiatric Symptoms; Cognitive Function; Hippocampus; Oxytocin; Immunological Parameters