Major depressive disorder: probiotics may be an adjuvant therapy

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Summary

Major depressive disorder (MDD) is an extremely complex and heterogeneous condition. Emerging research suggests that nutritional influences on MDD are currently underestimated. MDD patients have been shown to have elevated levels of pro-inflammatory cytokines, increased oxidative stress, altered gastrointestinal (GI) function, and lowered micronutrient and ω-3 fatty acid status. Small intestinal bacterial overgrowth (SIBO) is likely contributing to the limited nutrient absorption in MDD. Stress, a significant factor in MDD, is known to alter GI microflora, lowering levels of lactobacilli and bifidobacterium. Research suggests that bacteria in the GI tract can communicate with the central nervous system, even in the absence of an immune response. Probiotics have the potential to lower systemic inflammatory cytokines, decrease oxidative stress, improve nutritional status, and correct SIBO. The effect of probiotics on systemic inflammatory cytokines and oxidative stress may ultimately lead to increased brain derived neurotrophic factor (BDNF). It is our contention that probiotics may be an adjuvant to standard care in MDD.

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

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