Major depressive disorder: probiotics may be an adjuvant therapy.

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Major depressive disorder: probiotics may be an adjuvant therapy. 10.1016/j.mehy.2004.08.019
Title Major depressive disorder: probiotics may be an adjuvant therapy.
Authors AC Logan,M Katzman,
Journal Medical hypotheses
Issue 3
Issn 0306-9877
Doi 10.1016/j.mehy.2004.08.019
PMID 15617861
Volume 64
Pages 533-8
Publication Year 2005


  • Major depressive disorder (MDD) , , life illness.
  • Research influences MDD [1].
  • Some beneficial bacteria, states stress and illness, influence depression by a number of mechanisms.
  • research suggests that alterations

  • intestinal microflora may non-immune manifestations gastrointestinal (GI) tract.
  • Probiotic therapy beneficial bacteria improve balance host.
  • goal report branches research order hypothesis, probiotic bacteria may potential therapy MDD treatment.

Normal microflora

  • human GI tract complex ecosystem 500

  • species 200 genera.
  • number factors variety location bacteria in the intestines, stomach acid secretion bowel motility.
  • Two genera bacteria, lactobacilli and bif-idobacterium, beneficial effects human body.
  • bacteria vitamin synthesis, stimulation system, prevention colonization, protection barrier defense system, production chain fatty acids enterocyte energy, metabolism substances lowering levels components [2].
  • strains of probiotics cytokine secretion and antioxidants beyond the GI tract [3,4].
  • Emerging research suggests fats, x-3 fatty acids , relationship potential probiotics [5].

Intestinal flora in MDD related conditions

  • no reports state intestinal microflora human depression, there is some evidence conditions where depressive symptoms are part picture.
  • 30% MDD have irritable bowel syndrome (IBS).
  • IBS patients shown decreased lactoba-cilli, bifidobacterium, coliforms increased aerobes reduction anaerobe aerobe ratio.
  • use shown risk factor onset IBS.

  • Research has disease increased risk MDD (2.7-fold higher vs. controls) and attention deficit hyperactivity disorder (2.7-fold higher).
  • x-3 fatty acids thread , suggest intestinal microflora may .
  • intestinal microflora dermatitis shown significantly lower levels of bifidobacterium and higher levels staphylococcus.
  • Percentages bifidobacteria significantly lower patients with atopy vs. symptoms [6].

  • Pediatric recurrent abdominal pain colic found associated behavi-oral problems life.
  • recurrent abdominal pain childhood anxiety depressive disorders adulthood.
  • investigators reported levels lactoba-cilli lower cases colic vs. controls [7].

  • Chronic Fatigue Syndrome (CFS) fibromyalgia (FM) conditions where depressive symptoms reported.
  • Researchers lower levels of bifidobacterium and higher levels enterococcus spp these patients.
  • Interestingly, shown higher count CFS/FM patients, more defi-cits; nervousness, memory loss, forgetfulness confusion [8].
  • All symptoms MDD.

  • Endometriosis (EM) is a condition where depressive symptoms , lactobacilli levels low.
  • four conditions -- EM, IBS, CFS FM -- migration of bacteria colon into the small intestine .
  • result small intestinal bacterial overgrowth (SIBO) conditions by lactulose hydrogen breath test.
  • Migration of bacteria into the small intestine associated higher levels pain [9].
  • SIBO has not investigated MDD, these patients result intestinal stasis low stomach acid secretion.
  • Patients with depression are known to have low levels stomach acid production intestinal stasis.
  • Cytokines depressive symptoms, interleukin 1-beta (Il-1b) tumor necrosis factor alpha (TNFa), acid secretion.
  • addition, inactivity, to depression, associated SIBO.
  • Various strains of probiotics have been shown treatment of SIBO [10].

  • significance SIBO to depression not only complaints MDD, malabsorption fat, carbohydrate, protein, B vitamins other micronutrients.
  • nutrient levels may turn host defense SIBO.
  • Patients with depression are known to have low levels acid, vitamins B 12 ,B 6 zinc [11--14].
  • Low levels vitamin B 6 associated conversion alpha acid mood eicosapentaenoic acid (EPA).
  • Non-digestible oligosaccharides increase availability nutrients zinc, effects increased bifidobacterium.
  • treatment of SIBO led improvements depression, memory concentration CFS patients [15].

  • note Crohn's disease is a condition where depression diagnosis more than by chance.
  • deficits patients with Crohn's disease, depression

  • relapses.
  • microflora Crohn's disease reported low numbers of lactobacilli [16].

Stress, MDD and microflora

  • life events associated first onset depression episodes MDD.
  • research relationship , least part, one.
  • influence stress intestinal microflora subject some research animals humans.
  • animal studies indicate that stressors increase bacteria and decrease lactobacilli [17,18].
  • Restraint conditions, stress and food deprivation all shown microflora animal studies [19--21].

  • Lower lactobacilli levels display stress-indicative behaviors animals.
  • GI flora result changes gut motility, GI acidity and/or effect neurochemicals such as norepinephrine [22].
  • stress pregnancy result in reduction lactobacilli and bifido-bacterium offspring, controls [23].
  • Measures infant independence infant anaerobes, lactobacilli and bifidobacte-rium concentrations [23].
  • research connection between str-essors depression offspring.

  • evidence from human studies indicating that stress can microflora [24,25].
  • Emotional stress lead term reductions lactobacilli and bifidobacterium [26].
  • Bifidobacterium extre-mely emotional stress.
  • Restraint stress and demands lead decreases lactobacilli and bifidobacterium humans [27].

Depression and cytokines

  • Elevations pro-inflammatory cytokines such as interferon gamma (INFc), TNFa, 1L-6 1L-1b all MDD.
  • fact, elevations 1L-1b TNFa associated severity depression.
  • Pro-inflammatory cytokines mood by a number of mechanisms, lowering neurotransmitter precursor availability, activation hypothalamic-pituitary axis, alteration metabolism neurotransmitters neurotransmitter transporter mRNA [28].

  • Nerve growth factors, brain derived neurotrophic factor (BDNF), role plasticity survival nervous system depression-associated atrophy hippocampus cortex.
  • BDNF lower MDD, severity depressive symptoms [29].
  • Inhibition inflammatory cytokines by antidepressants lead increased BDNF.

  • Research suggests that cytokine elevation periphery not symptoms, alterations sleepwake behavior some orders magnitude levels found inflammation, infection immunopathology.
  • evidence suggests cytokines influence brain functions, levels low [30].

Depression and oxidative stress

  • human study found depressive symptoms lipid peroxidation females.
  • Patients with obsessive compulsive disorder (OCD) co-morbid MDD have higher levels lipid peroxidation than OCD .
  • interventions influence antioxidant defense system, bioavailability antioxidant phytochemicals composition intestinal microflora [31].
  • x-3 Fatty acids have shown decrease lipid peroxidation antioxidant supplementation influence fat BDNF levels function rats.

Omega-3, lipids and microflora

  • Research has shown fish consumption reduce risk MDD, seasonal affective disorder, disorder post-partum depression.
  • evidence by wealth animal research.
  • studies have beneficial effects x-3 fatty acids disorders.
  • EPA candidate treatment MDD [1].

  • contrast increased incidence depression, intake x-3 fatty acids has declined countries last 100 years.
  • result supply omega-6 oils (corn, safflower, sunflower, cottonseed)

  • food supply animal rearing.
  • There is some evidence scale changes fat intake significantly influence intestinal microflora, , turn, intestinal microflora influence x-3 levels.

  • studies suggest fat types intestinal flora.
  • study involving mice three different groups; 10% corn oil, or 1% corn oil and 9% fish oil, or 1% corn oil and 9% beef fat.
  • fish oil diet led three increase bifidobacteria levels and lowest levels bacteroides other groups [32].
  • studies have shown omega-6 corn oil and acid growth bifido-bacteria.
  • contrast, EPA human bacteroides [33].
  • Arctic charr, found either 4% fish oil 7% flax oil diet increase lactic acid bacteria, lactobacilli .
  • Coconut oil not raise lactic acid bacteria microflora [34].

  • fats effect on adhesion probiotics to intestinal cells.
  • acid less adhesion, flax-seed oil increase adhesion to intestinal cells.
  • Seal oil, high EPA, shown increase adhesion lactobacillus paracasei by 12% intestines [35].
  • Fatty acids bacteria and potential structure, probiotic adhesion.

  • relationship between x-3 fatty acids probiotics may bi-directional, research shows bifidbacterium (Bb-12), infants 7 months, increases amount alpha-linolenic acid plasma phospholipids [36].
  • study involving hens, shown egg EPA levels significantly increased lactoba-cillus probiotic flaxseed feed vs. flaxseed [37].

  • prevalence MDD and seasonal affective disorder lower Japan compared to Canada.
  • numbers of lactobacilli bifido-bacterium higher adults vs. Canada.
  • effect intestinal flora probiotics on x-3 status, influence fish oil bacteria investigation.

Probiotics to augment treatment of depression?

  • gut 100 million neurons; GI tract meeting place nerves,

  • microorganisms cells.
  • Microorganisms host neuroendocrine environment , , bacteria influence neuroendocrine environment by production neurochemicals such as gamma amino butyric acid (GABA), serotonin, peptides.

  • Animal studies indicate that GI microorganisms pathways, absence immune response.
  • Campylobacter jejuni, doses low activation, result in anxiety effects mice [38].
  • addition, confirmed C. jejuni nuclei brainstem, counts low immune response.
  • areas brainstem activation, nucleus tract nucleus, are part set nuclei information processing lead , responses bacteria [39].

  • Probiotic bacteria may influence mood by effect on cytokine production.
  • most research probiotics and cytokine release GI effects, evidence systemic effect.
  • various strains of probiotics have been shown 1L-1b, TNFa, IL-6 INFc beyond the GI mucosa periphery [40].
  • potential role low levels cytokines MDD, studies effect of probiotics on cytokines behavior.
  • systemic effect probiot-ics , leading reductions inflammation rats [41].
  • effects of probiotics on inflammatory cytokines influence MDD and BDNF levels.

  • Probiotic therapy shown improve lactose maldigestion, finding lactose malabsorption associated signs MDD [42].
  • lactose malabsorption, high lactose concentrations LL-tryptophan metabolism serotonin availability.
  • Probiotics have studies involving IBS patients [43] rises enterococci levels, bacteria associated dysfunction CFS.
  • Probiotics have been shown improve well-being patients with arthritis [44] reported reduce effects medications [45].
  • combination probiotic cultures multivitamin/minerals shown improve depressive symptoms group adults stress [46].

  • considerations MDD and probiotics influence beneficial bacteria B vitamin status [47], , , x-3 status mineral absorption.
  • ability of probiotics antioxidants, prevention lipid peroxidation [48], effects MDD.
  • ability of probiotics SIBO [10] influence MDD.

  • research suggests that probiotics have potential MDD treatment.
  • potential of probiotics x-3 fatty acids together area potential research MDD.
  • microbes GI tract functions human body nervous systems.
  • contention role intestinal microflora, potential of probiotics MDD, exploration.