Effects of a Psychobiotic Supplement on Serum Brain-derived Neurotrophic Factor Levels in Depressive Patients: A  Post Hoc  Analysis of a Randomized Clinical Trial

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Abstract

Background/Aims

Psychobiotics are probiotics or prebiotics that, upon ingestion in adequate amounts, yield positive influence on mental health via microbiota-gut-brain axis regulation to modulate the circulating cytokines, chemokines, neurotransmitters, or neurotrophins levels. We have recently shown that a psychobiotic combination ( Lactobacillus helveticus R0052 and Bifidobacterium longum R0175; CEREBIOME) significantly improved depression symptoms in patients with depression. Recent animal data suggest the influence of the gut microbiota on brain-derived neurotrophic factor (BDNF), which was shown to correlate with antidepressant response in depressive patients. Therefore, we conducted this exploratory post hoc analysis of BDNF levels to clarify the mechanism of action of this psychobiotic in our cohort.

Methods

Our study was a double-blind, randomized controlled trial of patients with low-to-moderate depression receiving either a probiotic combination, prebiotic or placebo. From the 110 patients randomized in the trial, 78 were included in this post hoc analysis (probiotic, n = 28; prebiotic and placebo, n = 25). We compared serum BDNF levels from participants at baseline and endpoint, and assessed the Pearson correlation between depression severity and BDNF levels for each intervention.

Results

We found that post-intervention BDNF levels were significantly different between groups ( P < 0.001). Furthermore, BDNF levels increased significantly in the probiotic group compared to both the prebiotic ( P < 0.001) and placebo groups ( P = 0.021), which inversely correlated with depression severity compared to placebo (ANOVA/ANCOVA, P = 0.012; Pearson, r = –0.79, P < 0.001). In the prebiotic group, BDNF levels reduced but not significantly compared with placebo group ( P > 0.05).

Conclusion

Eight-week supplementation with B. longum and L. helveticus in depressive patients improved depression symptoms, possibly by increasing BDNF levels.

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Most cited references 42

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Psychobiotics: a novel class of psychotropic.

Timothy Dinan, Ann-Catherine J. Stanton, John F. Cryan (2013)

Here, we define a psychobiotic as a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis. Preclinical evaluation in rodents suggests that certain psychobiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems. So far, psychobiotics have been most extensively studied in a liaison psychiatric setting in patients with irritable bowel syndrome, where positive benefits have been reported for a number of organisms including Bifidobacterium infantis. Evidence is emerging of benefits in alleviating symptoms of depression and in chronic fatigue syndrome. Such benefits may be related to the anti-inflammatory actions of certain psychobiotics and a capacity to reduce hypothalamic-pituitary-adrenal axis activity. Results from large scale placebo-controlled studies are awaited. © 2013 Society of Biological Psychiatry.

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Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects.

Michaël Messaoudi, Robert Lalonde, Nicolas Violle … (2011)

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.

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BDNF - a key transducer of antidepressant effects.

Carl Björkholm, Lisa M. Monteggia (2016)

How do antidepressants elicit an antidepressant response? Here, we review accumulating evidence that the neurotrophin brain-derived neurotrophic factor (BDNF) serves as a transducer, acting as the link between the antidepressant drug and the neuroplastic changes that result in the improvement of the depressive symptoms. Over the last decade several studies have consistently highlighted BDNF as a key player in antidepressant action. An increase in hippocampal and cortical expression of BDNF mRNA parallels the antidepressant-like response of conventional antidepressants such as SSRIs. Subsequent studies showed that a single bilateral infusion of BDNF into the ventricles or directly into the hippocampus is sufficient to induce a relatively rapid and sustained antidepressant-like effect. Importantly, the antidepressant-like response to conventional antidepressants is attenuated in mice where the BDNF signaling has been disrupted by genetic manipulations. Low dose ketamine, which has been found to induce a rapid antidepressant effect in patients with treatment-resistant depression, is also dependent on increased BDNF signaling. Ketamine transiently increases BDNF translation in hippocampus, leading to enhanced synaptic plasticity and synaptic strength. Ketamine has been shown to increase BDNF translation by blocking NMDA receptor activity at rest, thereby inhibiting calcium influx and subsequently halting eukaryotic elongation factor 2 (eEF2) kinase leading to a desuppression of protein translation, including BDNF translation. The antidepressant-like response of ketamine is abolished in BDNF and TrkB conditional knockout mice, eEF2 kinase knockout mice, in mice carrying the BDNF met/met allele, and by intra-cortical infusions of BDNF-neutralizing antibodies. In summary, current data suggests that conventional antidepressants and ketamine mediate their antidepressant-like effects by increasing BDNF in forebrain regions, in particular the hippocampus, making BDNF an essential determinant of antidepressant efficacy.

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Author and article information

Journal

Journal ID (nlm-ta): J Neurogastroenterol Motil

Journal ID (iso-abbrev): J Neurogastroenterol Motil

Title: Journal of Neurogastroenterology and Motility

Publisher: The Korean Society of Neurogastroenterology and Motility

ISSN (Print): 2093-0879

ISSN (Electronic): 2093-0887

Publication date (Print): 30 September 2020

Publication date (Electronic): 30 September 2020

Volume: 26

Issue: 4

Pages: 486-495

Affiliations

[1 ]Department of Nutrition and Dietetics, Hacettepe University Faculty of Health Sciences, Ankara, Turkey

[2 ]Nutrition Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

[3 ]Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran

Author notes

[* ]Correspondence: Asma Kazemi and Kurosh Djafarian are equally responsible for this study. Asma Kazemi, PhD, Nutrition Research Canter, Shiraz University of Medical Sciences, PO Box 71645-111, Shiraz, Iran, Tel: +98713612206, E-mail: kazemiasma66@ 123456gmail.com Kurosh Djafarian, PhD, Department of Clinical Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, No. 44, Hojjat-dost Alley, Naderi St., Keshavarz Blvd, 14166/43931, Tehran, Iran, Tel: +98 912 6654577, Fax: +98 (0) 21 88974462, E-mail: kdjafarian@ 123456tums.ac.ir

Article

Publisher ID: JNM-26-486

DOI: 10.5056/jnm20079

PMC ID: 7547201

PubMed ID: 32989186

SO-VID: e155bf26-b2a0-444a-89f7-f70a6efdd85f

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 17 April 2020

Date revision received : 15 June 2020

Date accepted : 21 July 2020

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Effects of a Psychobiotic Supplement on Serum Brain-derived Neurotrophic Factor Levels in Depressive Patients: A Post Hoc Analysis of a Randomized Clinical Trial

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Karger: Neurology and Neuroscience

Most cited references 42

Psychobiotics: a novel class of psychotropic.

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects.

BDNF - a key transducer of antidepressant effects.

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Cited by 35

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