A Randomized Controlled Trial to Examine the Impact of a Multi-strain Probiotic on Self-reported Indicators of Depression, Anxiety, Mood, and Associated Biomarkers

Overview

Journal Front Nutr

Specialty Nutritional Sciences

Date 2023 Sep 18

PMID 37720373

Authors

Kylie E Walden

Jessica M Moon

Anthony M Hagele

Leah E Allen

Connor J Gaige

Joesi M Krieger

Ralf Jager

Petey W Mumford

Marco Pane

Chad M Kerksick

Affiliations

Soon will be listed here.

Abstract

Objective: To examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels.

Method: In a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m) supplemented with a single capsule of MSP (a total daily dose of 4 × 10 colony forming units [CFU] comprised of a 1 × 10 CFU dose from each of the following strains: LF16, LR06, LP01, and 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6 weeks of supplementation and 3 weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined.

Results: BDI, STAI, and total LEIDS-R scores were reduced from baseline ( < 0.05) with MSP supplementation after 4 and 6 weeks of supplementation and 3 weeks after supplementation while no changes ( > 0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower ( < 0.05) after supplementation. Plasma serotonin concentrations in MSP were increased from baseline after 6 weeks of supplementation and 3 weeks after ceasing supplementation. No changes ( > 0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups.

Conclusion: MSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6 weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortisol.

Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT05343533, NCT05343533.

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References

Bravo J, Forsythe P, Chew M, Escaravage E, Savignac H, Dinan T . Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011; 108(38):16050-5. PMC: 3179073. DOI: 10.1073/pnas.1102999108. View

Steenbergen L, Sellaro R, van Hemert S, Bosch J, Colzato L . A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015; 48:258-64. DOI: 10.1016/j.bbi.2015.04.003. View

Nobis A, Zalewski D, Waszkiewicz N . Peripheral Markers of Depression. J Clin Med. 2020; 9(12). PMC: 7760788. DOI: 10.3390/jcm9123793. View

Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan T . The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008; 43(2):164-74. DOI: 10.1016/j.jpsychires.2008.03.009. View

Ahmed H, Leyrolle Q, Koistinen V, Karkkainen O, Laye S, Delzenne N . Microbiota-derived metabolites as drivers of gut-brain communication. Gut Microbes. 2022; 14(1):2102878. PMC: 9341364. DOI: 10.1080/19490976.2022.2102878. View

Benton D, Williams C, Brown A . Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2006; 61(3):355-61. DOI: 10.1038/sj.ejcn.1602546. View

Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan J, Dinan T . Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010; 170(4):1179-88. DOI: 10.1016/j.neuroscience.2010.08.005. View

Chen H, Nwe P, Yang Y, Rosen C, Bielecka A, Kuchroo M . A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology. Cell. 2019; 177(5):1217-1231.e18. PMC: 6536006. DOI: 10.1016/j.cell.2019.03.036. View

Marotta A, Sarno E, Del Casale A, Pane M, Mogna L, Amoruso A . Effects of Probiotics on Cognitive Reactivity, Mood, and Sleep Quality. Front Psychiatry. 2019; 10:164. PMC: 6445894. DOI: 10.3389/fpsyt.2019.00164. View

10.

Smith K, Greene M, Babu J, Fruge A . Psychobiotics as treatment for anxiety, depression, and related symptoms: a systematic review. Nutr Neurosci. 2019; 24(12):963-977. DOI: 10.1080/1028415X.2019.1701220. View

11.

Scheier M, Carver C, Bridges M . Distinguishing optimism from neuroticism (and trait anxiety, self-mastery, and self-esteem): a reevaluation of the Life Orientation Test. J Pers Soc Psychol. 1994; 67(6):1063-78. DOI: 10.1037//0022-3514.67.6.1063. View

12.

Mao J, Kim Y, Zhou Y, Hu D, Zhong C, Chang H . Genetic and metabolic links between the murine microbiome and memory. Microbiome. 2020; 8(1):53. PMC: 7164142. DOI: 10.1186/s40168-020-00817-w. View

13.

Desbonnet L, Clarke G, Traplin A, OSullivan O, Crispie F, Moloney R . Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. Brain Behav Immun. 2015; 48:165-73. DOI: 10.1016/j.bbi.2015.04.004. View

14.

Liu G, Chong H, Chung F, Li Y, Liong M . DR7 Modulated Bowel Movement and Gut Microbiota Associated with Dopamine and Serotonin Pathways in Stressed Adults. Int J Mol Sci. 2020; 21(13). PMC: 7370301. DOI: 10.3390/ijms21134608. View

15.

Dalile B, Van Oudenhove L, Vervliet B, Verbeke K . The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019; 16(8):461-478. DOI: 10.1038/s41575-019-0157-3. View

16.

Christiansen C, Gabe M, Svendsen B, Dragsted L, Rosenkilde M, Holst J . The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. Am J Physiol Gastrointest Liver Physiol. 2018; 315(1):G53-G65. DOI: 10.1152/ajpgi.00346.2017. View

17.

Asano Y, Hiramoto T, Nishino R, Aiba Y, Kimura T, Yoshihara K . Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice. Am J Physiol Gastrointest Liver Physiol. 2012; 303(11):G1288-95. DOI: 10.1152/ajpgi.00341.2012. View

18.

Cummings D, King D, Mainous A, Geesey M . Combining serum biomarkers: the association of C-reactive protein, insulin sensitivity, and homocysteine with cardiovascular disease history in the general US population. Eur J Cardiovasc Prev Rehabil. 2006; 13(2):180-5. DOI: 10.1097/01.hjr.0000185973.59512.d3. View

19.

Ford E, Ajani U, Mokdad A . The metabolic syndrome and concentrations of C-reactive protein among U.S. youth. Diabetes Care. 2005; 28(4):878-81. DOI: 10.2337/diacare.28.4.878. View

20.

Ajani U, Ford E, Mokdad A . Dietary fiber and C-reactive protein: findings from national health and nutrition examination survey data. J Nutr. 2004; 134(5):1181-5. DOI: 10.1093/jn/134.5.1181. View