Major depressive disorder: probiotics may be an adjuvant therapy
Introduction
Major depressive disorder (MDD) is a recurrent, debilitating, and potentially life threatening illness. Research indicates that nutritional influences on MDD are currently underestimated [1]. Some potentially beneficial bacteria, which are lowered in states of stress and chronic illness, may potentially influence depression by a number of mechanisms. Emerging research suggests that alterations in the intestinal microflora may have immune and non-immune manifestations beyond the gastrointestinal (GI) tract. Probiotic therapy is generally defined as using beneficial bacteria to improve the intestinal microbial balance of the host. The goal of this report is to integrate various branches of research in order to support our hypothesis, that probiotic bacteria may have potential as an adjuvant therapy in MDD treatment.
Section snippets
Normal microflora
The human GI tract contains a complex and delicately balanced ecosystem of 500 bacterial species belonging to about 200 genera. A number of factors will determine the variety and location of bacteria in the intestines, including stomach acid secretion and small bowel motility. Two particular genera of bacteria, lactobacilli and bifidobacterium, are well documented to have beneficial effects in the human body. These bacteria are involved in vitamin synthesis, stimulation of the immune system,
Intestinal flora in MDD related conditions
While there have been no published reports on the state of intestinal microflora in human depression, there is some evidence from associated conditions where depressive symptoms are part of the picture. Approximately 30% of those with MDD have diagnosable irritable bowel syndrome (IBS). IBS patients have been shown to have decreased lactobacilli, bifidobacterium, coliforms as well as increased aerobes and a reduction of the normal anaerobe to aerobe ratio. Prior antibiotic use has been shown to
Stress, MDD and microflora
Stressful life events are strongly associated with first onset of major depression and with subsequent episodes of MDD. The research also indicates that the relationship is, at least in part, a causal one. The influence of stress on the intestinal microflora has been the subject of some research in animals and humans. The animal studies indicate that environmental stressors can increase aerobic bacteria and decrease lactobacilli [17], [18]. Restraint conditions, acoustic stress and food
Depression and cytokines
Elevations in pro-inflammatory cytokines such as interferon gamma (INFγ), TNFα, 1L-6 and 1L-1β have all been observed in MDD. In fact, elevations in 1L-1β and TNFα are associated with the severity of depression. Pro-inflammatory cytokines can affect mood by a number of mechanisms, including lowering of neurotransmitter precursor availability, activation of the hypothalamic-pituitary adrenal axis, and alteration of metabolism of neurotransmitters and neurotransmitter transporter mRNA [28].
Nerve
Depression and oxidative stress
A recent human study found that depressive symptoms are independently correlated with lipid peroxidation in Japanese females. Patients with obsessive compulsive disorder (OCD) and co-morbid MDD have higher levels of lipid peroxidation than those with OCD alone. Dietary interventions are known to influence the antioxidant defense system, and the bioavailability of dietary antioxidant phytochemicals may be dependent upon the composition of the intestinal microflora [31]. ω-3 Fatty acids have been
Omega-3, lipids and microflora
Research has shown that dietary fish consumption may reduce the risk of MDD, seasonal affective disorder, bipolar disorder and post-partum depression. The epidemiological evidence is supported by a wealth of experimental and animal research. Clinical studies have demonstrated beneficial effects of ω-3 fatty acids in various psychiatric disorders. EPA has emerged as a strong candidate for the treatment of MDD [1].
In contrast to the increased incidence of depression, the dietary intake of ω-3
Probiotics to augment treatment of depression?
The gut contains over 100 million neurons; the GI tract is ultimately a meeting place of nerves, microorganisms and immune cells. Microorganisms are responsive to the host’s neuroendocrine environment and, conversely, bacteria can influence the neuroendocrine environment by the production of neurochemicals such as gamma amino butyric acid (GABA), serotonin, and various biologically active peptides.
Animal studies indicate that GI microorganisms can directly activate neural pathways, even in the
References (48)
- et al.
Overview of gut flora an probiotics
Int J Food Microbiol
(1998) - et al.
Differences in fecal microflora between patients with atopic dermatitis and healthy control subjects
J Allergy Clin Immunol
(2003) - et al.
Eradication of small intestinal bacterial overgrowth decreases symptoms in chronic fatigue syndrome: a double blind, randomized study
Gastroenterology
(2000) Problems of microbial ecology in man space missions
Acta Astronaut
(1991)- et al.
Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants
Biol Psychiatry
(2003) - et al.
Low levels of circulating inflammatory cytokines – do they affect human brain functions?
Brain Behav Immun
(2002) - et al.
Polyphenols: food sources and bioavailability
Am J Clin Nutr
(2004) - et al.
Influence of probiotic supplemented infant formula on composition of plasma lipids in atopic infants
J Nutr Biochem
(2002) - et al.
Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation
Physiol Behav
(1998) - et al.
Brain response to cecal infection with Campylobacter jejune: analysis with Fos immunohistochemistry
Brain Behav Immun
(2004)
Lactobacillus GG bacteria ameliorate arthritis in Lewis rats
J Nutr
Bacterially synthesized folate in rat large intestine is incorporated into host tissue foly1 polyglutamates
J Nutr
Food, micronutrients, and psychiatry
Int Psychogeriatr
Is the mucosa route of administration essential for probiotic function? subcutaneous administration is associated with attenuation of murine colitis and arthritis
Gut
Antioxidative probiotic fermented goats’ milk decreases oxidative stress-mediated atherogenicity in human subjects
Br J Nutr
Improvement of the probiotic effect of micro-organisms by their combination with maltodextrins, fructo-oligosaccharides and polyunsaturated fatty acids
Br J Nutr
Intestinal microflora in breastfed colicky and non-colicky infants
Acta Paediatr
A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing
Ann Rheum Disease
Effect of Lactobacillus strains (L. casei and L. acidophilus strains cerela) on bacterial overgrowth-related chronic diarrhea
Medicina (B Aires)
Depression and folate status in the US population
Psychother Psychosom
Vitamin B12, folate, and homocysteine in depression: the Rotterdam study
Am J Psychiatry
Low B6 levels in depressed outpatients
Biol Psychiatry
Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study
Pol J Pharmacol
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