Fermented Milk Product With Probiotic and Its Impact on Mood of Patients With Treatment Resistant Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional

Summary: 
      This study aims to assess the impact of a chronic dietary intervention (8 weeks) with
      probiotics, specifically Fermented Milk Product with Probiotic (FMPP), on the mood of
      individuals with Major Depressive Disorder (MDD) refractory to standard antidepressant
      therapy, and its association with changes in intestinal microbiota and markers of
      inflammation.
    

Detailed description: 
      Theories about the association of imbalances in the gastro-intestinal (GI) microbiota and its
      impact on mood states have long existed in medicine. These theories were considered "dead"
      for most of the 20th century, but converging lines of evidence are now rekindling interest in
      a link between the GI microbiota and the central nervous system. Newer lines of investigation
      have made these dormant theories relating commensal microbiota and mood states not only
      plausible, but the focus of well-designed basic research studies (Yano et al, 2015; Hsiao et
      al, 2013). The microbial world influence on brain development and behavior was defined by Dr
      Tom Insel, the former director of the National Institutes of Mental Health as one the "great
      frontiers" of neuroscience in the next decade (Insel, 2012). Dr. Francis Collins, Director of
      the National Institutes of Health, further underscored the need for research on the impact of
      intestinal microbiota on brain function (Collins, 2014).

      This renewed interest in understanding the role of the microbiota beyond the digestive tract
      was spurred in 2007 when the Human Microbiome Project was launched. (Turnbaugh et al, 2007).
      With over one million different genes and a mass equal to that of the human brain, the
      genetic diversity of our bacterial commensals outnumbers the human genome by a factor of over
      100 to one, and suggests the potential for the genetic variability in the GI environment to
      impact other body systems, including the central nervous system (CNS). A range of
      neurotransmitters relevant to mood and anxiety disorders including serotonin, GABA,
      acetylcholine and endocannabinoids are produced by intestinal microbiota (Dinan et al, 2013).
      This accruing data along with previous findings showing that pathological gut bacterium are
      capable of inducing changes in behavior (Lyte et al, 1998) and that early life stress, an
      established risk factor for major depression, induces changes in the microbiota (O'Mahony et
      al, 2007) underscore the potential importance of further examining the relationship between
      the microbiota and brain function with particular attention to the potential therapeutic
      implications for treatment of psychiatric conditions, such as depression

      Preclinical studies demonstrated that noninvasive methods that alter gut microbiota are
      capable of inducing antidepressant like effects in rat models of depression (Desbonnet et al,
      2010). Findings in human populations showed differences in gut flora of depressed individuals
      when compared to healthy controls, including higher levels of Bacteroidetes, Proteobacteria
      and Actinobacteria, and a negative correlation between Faecalibacterium and the severity of
      their depression (Jiang et al, et al 2015). Other studies point to a beneficial effect of
      probiotics on mood and anxiety in normal volunteers (Messaoudi et al, 2011; Benton et al,
      2007), as well as in individuals with Irritable Bowel Syndrome (O' Mahoney et al, 2005) and
      Chronic Fatigue Syndrome (Rao et al, 2009). However, there have been no systematic studies to
      date reporting on the impact of probiotics on mood in individuals with major depression.

      The majority of depressed patients remain symptomatic despite treatment with currently
      available antidepressants, and a significant proportion do not respond at all. Thus, the
      development of new effective antidepressant interventions remains a significant unmet public
      health need. Given the accumulating evidence for a relationship between the gastrointestinal
      microbiota and the central nervous system functioning and pathophysiology, including that of
      affective disorders, it is cogent to measure the impact of probiotic interventions in
      individuals with refractory depression. The present study proposes to examine the gut
      microbiota, inflammatory milieu and impact of probiotics on mood in a population of
      individuals who have been refractory to treatment with standard antidepressant agents.

      This study aims to assess the impact of a chronic dietary intervention (8 weeks) with
      probiotics, specifically Fermented Milk Product with Probiotic (FMPP), on the mood of
      individuals with Major Depressive Disorder (MDD) refractory to standard antidepressant
      therapy, and its association with changes in intestinal microbiota and markers of
      inflammation.

      Specific Aim 1. Examine the effect of 8 weeks of probiotic administration on depressive
      symptoms in depressed patients.

      Specific Aim 2. Examine the intestinal microbiota at initiation and end of probiotic
      administration in order to assess the relationship of baseline and changes in gut flora with
      treatment response.

      Specific Aim 3. Examine baseline and endpoint inflammatory biomarkers including C-reactive
      protein (CRP) and cytokines to assess the relationship of inflammation with intestinal
      microbiota and treatment response.
    

Intervention name(s): BioKefir; Non-fermented milk
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): BKP BioKefir (Lifeway Foods) is a lactose-free fermented milk product containing 12 different bacteria provided in a drink.; A non-fermented milk drink.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment