Applied nutritional investigationClinical and metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial
Introduction
Major depressive disorder (MDD) is a complex and multifactorial disorder that involves marked disabilities in global functioning, anorexia, and severe medical comorbidities [1]. It affects around 20% of the population at some point during their lifetime [2]. Previous studies have shown a link between metabolic profiles, biomarkers of inflammation, oxidative stress, and MDD [1], [3], [4]. Depression or depressive episodes may affect cortisol dysregulation, which might in turn result in the development of insulin resistance in patients with depression [5]. In addition, recent studies have reported that decreased antioxidant levels, especially of glutathione (GSH), are associated with increased anhedonia severity, which subsequently might lead to involvement of neuroinflammation and oxidative stress in patients with MDD [6].
Probiotics are proposed to have a range of health benefits. Their beneficial impacts on a wide range of symptoms have been examined, including relief of irritable-bowel syndrome and inflammatory bowel disease, as well as the amelioration of lactose intolerance, and the prevention of bowel cancer [7], [8]. Moreover, emerging research has reported that the microflora of the intestines may affect the immune system and functioning beyond the gut [9]. Probiotics might have favorable effects on mood and psychological problems [10]. In a study by Mohammadi et al. [11], consumption of probiotic yogurt or a multispecies probiotic capsule for 6 wk had beneficial effects on mental health parameters in petrochemical workers. Other studies have also reported the favorable effects of probiotic administration in healthy subjects [12] and patients with chronic fatigue syndrome [13]. In a study by Benton et al. [14], consumption of probiotic yogurt improved the mood of those whose mood was initially poor. In addition, improved metabolic status, biomarkers of inflammation, and oxidative stress were observed after a 2-mo supplementation with probiotics in pregnant women and patients with type 2 diabetes mellitus [15], [16]. However, probiotic supplementation containing Lactobacillus rhamnosus strain GG and Bifidobacterium had no beneficial effects in people with schizophrenia after 14 wk [17].
Probiotics may result in reduced depressive symptoms, as well as improved metabolic status, biomarkers of inflammation, and oxidative stress, through their effect on neuronal circuits and the central nervous system mediated by the microbiota-gut-brain axis [18] and through affecting gene expression [19]. In addition, experimental studies in the animal model of depression have demonstrated that the oral administration of a probiotic can increase plasma tryptophan concentrations, decrease serotonin metabolite concentrations in the frontal cortex, and dopamine metabolite concentrations in the amygdaloid cortex [20]. However, whether probiotics have direct benefits on depressive symptoms and metabolic status in patients with MDD has to date not been assessed. The present study was therefore conducted to assess the favorable effects of probiotic supplementation on symptoms of depression, parameters of glucose homeostasis, lipid concentrations, biomarkers of inflammation, and oxidative stress in patients with MDD.
Section snippets
Participants
Forty patients with MDD whose age ranged between 20 and 55 y were recruited for this randomized, double-blind, placebo-controlled trial from July 2014 to September 2014. To determine the sample size, we applied a randomized clinical trial sample size formula considering type I (α) and type II errors (β) of 0.05 and 0.20 (power = 80%), respectively. On the basis of a previous study [11], we used a standard deviation (SD) of 18.5 and a difference in mean (d) of 18, considering depression anxiety
Results
In the probiotic group, three patients withdrew because of personal reasons (n = 3). In the placebo group, two patients withdrew because of personal reasons (n = 2). Finally, 35 persons (probiotic group, n = 17; placebo group, n = 18) completed the trial (Fig. 1). However, as the analysis was done based on the intention-to-treat approach, all 40 patients with MDD were included in the final analysis. In total, the rate of compliance in the present study was high, as more than 90% of capsules
Discussion
In the present study, we examined the beneficial effects of probiotic administration on BDI score, markers of insulin metabolism, lipid profiles, hs-CRP, and biomarkers of oxidative stress in patients with MDD. The main findings were that probiotic supplementation improved the BDI score and insulin function, and decreased oxidative stress in patients with MDD. To the best of our knowledge, this study is the first that reports the effect of probiotic administration on symptoms of depression,
References (45)
- et al.
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Neuroscience
(2015) - et al.
Relationship between hypothalamic-pituitary-adrenal axis dysregulation and insulin resistance in elderly patients with depression
Psychiatry Res
(2015) - et al.
In vivo H MRS study of potential associations between glutathione, oxidative stress and anhedonia in major depressive disorder
Neurosci Lett
(2014) - et al.
Major depressive disorder: probiotics may be an adjuvant therapy
Med Hypotheses
(2005) - et al.
Gut-brain axis: how the microbiome influences anxiety and depression
Trends Neurosci
(2013) - et al.
Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion
J Biol Chem
(2013) - et al.
The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat
J Psychiatr Res
(2008) - et al.
The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay
Anal Biochem
(1996) - et al.
Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus
J Dairy Sci
(2011) - et al.
Short communication: effect of supplementation with Lactobacillus casei Shirota on insulin sensitivity, beta-cell function, and markers of endothelial function and inflammation in subjects with metabolic syndrome—a pilot study
J Dairy Sci
(2013)
Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells
J Hepatol
Effects of synbiotic food consumption on metabolic status of diabetic patients: a double-blind randomized cross-over controlled clinical trial
Clin Nutr
Hepatocyte nuclear factor 4 alpha is a key factor related to depression and physiological homeostasis in the mouse brain
PLoS One
Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey replication
Arch Gen Psychiatry
Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder
PLoS One
Prophylactic and therapeutic uses of probiotics: a review
J Am Diet Assoc
Probiotics and chronic disease
J Clin Gastroenterol
Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects
Br J Nutr
The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: a randomized, double-blind, placebo-controlled trial in petrochemical workers
Nutr Neurosci
The effect of daily consumption of probiotic and conventional yoghurt on some oxidative stress factors in plasma of young healthy women
ARYA Atheroscler J
A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome
Gut Pathog
Impact of consuming a milk drink containing a probiotic on mood and cognition
Eur J Clin Nutr
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ZA. contributed to conception, design, statistical analysis, and drafting of the manuscript. G.A., Z.K.-P., M.T.-E., P.J., H.A., M.T., M.R.M., and A.E. contributed to data collection and manuscript drafting. Z.A. supervised the study. All authors approved the final version for submission. Clinical trial registration number: IRCT2014060717993 N1 (www.irct.ir). The present study was supported by a grant (no. 9344) from the vice chancellor for research, Kashan University of Medical Sciences, Iran. The authors would like to thank the staff of Kargarneghad Hospital (Kashan, Iran) for their assistance in this project. None of the authors had any personal or financial conflict of interest.