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Effects of a multi-strain probiotic on hippocampal structure and function, cognition, and emotional well-being in healthy individuals: a double-blind randomised-controlled trial

Published online by Cambridge University Press:  06 May 2022

Leonie Ascone Open the ORCID record for Leonie Ascone [Opens in a new window] ,
Caroline Garcia Forlim ,
Jürgen Gallinat  and
Simone Kühn
Leonie Ascone*
Affiliation:
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
Caroline Garcia Forlim
Affiliation:
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
Jürgen Gallinat
Affiliation:
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
Simone Kühn
Affiliation:
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany Max Planck Institute for Human Development, Lise Meitner Group for Environmental Neuroscience, Lentzeallee 94, 14195 Berlin, Germany
*
Author for correspondence: Leonie Ascone, E-mail: l.ascone-michelis@uke.de
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Abstract

Background

Animal studies have shown beneficial effects of probiotic supplementation on the hippocampus (HC) and cognitive performance. Evidence in humans is scarce. It was hypothesised that probiotic supplementation is associated with enhanced hippocampal (HC) regional grey matter volume (rGMV), as well as HC functional connectivity (FC). Relatedly improvements in mnestic and navigational performance, or emotional well-being, were expected to be observed in healthy human volunteers.

Methods

A randomised-controlled, double-blind trial (RCT) was conducted in N = 59 volunteers (age Mean = 27.1, s.d. = 6.7), applying a multi-strain probiotic (Vivomixx®) v. non-probiotic milk-powder placebo, each with 4.4 g/day, for 4 weeks. Volumetric data was extracted from 3T structural magnetic resonance images of total HC and -subfields. Voxel-based morphometry (VBM) and FreeSurfer-based analyses were performed. Potential neuroplastic change beyond HC was explored using whole-brain-VBM for white- and GMV. Seed-based FC was calculated based on HC. Cognitive tests included visual, map-based, object-location, and verbal memory, and spatial navigation. Mental health status (stress, anxiety, depression, and emotion-regulation) was assessed using self-reports.

Results

There were no changes in HC-total, -subfield GMV, or FC, through probiotics. VBM revealed no changes at a whole-brain-level. There were no effects on cognitive performance or mental health. Evidence in favor of the null-hypothesis, using Bayesian statistics, was consistent.

Conclusions

The applied multi-strain probiotic did not elicit any effects concerning hippocampal structural plasticity, cognition, or mental well-being in young, healthy adults. For future studies, longer application/observation RCTs, perhaps in stressed, otherwise psychologically/ cognitively vulnerable, or ageing groups, with well-founded strain selection and investigation of mechanism, are advised.

Keywords

Cognitionhippocampusmental healthmulti-strain probiotic supplementneuroimaging
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 16 , December 2022 , pp. 4197 - 4207
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Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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References

Bagga, D., Aigner, C. S., Reichert, J. L., Cecchetto, C., Fischmeister, F. P. S., Holzer, P., … Schöpf, V. (2018a). Influence of 4-week multi-strain probiotic administration on resting-state functional connectivity in healthy volunteers. European Journal of Nutrition, 58(5), 1821–1827. doi: 10.1007/s00394-018-1732-z.CrossRefGoogle ScholarPubMed
Bagga, D., Reichert, J. L., Koschutnig, K., Aigner, C. S., Holzer, P., Koskinen, K., … Schöpf, V. (2018b). Probiotics drive gut microbiome triggering emotional brain signatures. Gut Microbes, 9(6), 486–496. doi: 10.1080/19490976.2018.1460015.Google ScholarPubMed
Beck, A. T., Steer, R. A., & Brown, G. (2011). Manual for the Beck depression inventory-II. San Antonio, TX: Psychological Corporation.Google Scholar
Chao, L., Liu, C., Sutthawongwadee, S., Li, Y., Lv, W., Chen, W., … Guo, S. (2020). Effects of probiotics on depressive or anxiety variables in healthy participants under stress conditions or with a depressive or anxiety diagnosis: A meta-analysis of randomized controlled trials. Frontiers in Neurology, 11, 421. doi: 10.3389/fneur.2020.00421.CrossRefGoogle ScholarPubMed
Cohen, S., Kamarck, T., & Mermelstein, R. (1993). A global measure of perceived stress. Journal of Health and Social Behavior, 24, 385–396. doi: 10.2307/2136404.CrossRefGoogle Scholar
Derogatis, L. R., & Melisaratos, N. (1983). The brief symptom inventory: An introductory report. Psychological Medicine, 13(3), 595–605. doi: 10.1017/S0033291700048017.CrossRefGoogle ScholarPubMed
Distrutti, E., O'Reilly, J.-A., McDonald, C., Cipriani, S., Renga, B., Lynch, M. A., & Fiorucci, S. (2014). Modulation of intestinal microbiota by the probiotic VSL#3 resets brain gene expression and ameliorates the age-related deficit in LTP. PLoS One, 9(9), e106503. doi: 10.1371/journal.pone.0106503.CrossRefGoogle Scholar
Franke, G. H. (2000). Brief symptom inventory (BSI) von L.R. Derogatis: (Kurzform der SCL-90-R), [Brief symptom inventory (BSI) of L. R. Derogatis: (Short-form of SCL-90-R)]. Göttingen: Beltz Test.Google Scholar
Government of Canada, Health Canada. (2009, April 16). Accepted claims about the nature of probiotic microorganisms in Food. Retrieved from https://www.canada.ca/en/health-canada/services/food-nutrition/food-labelling/health-claims/accepted-claims-about-nature-probiotic-microorganisms-food.html.Google Scholar
Gramann, K., Onton, J., Riccobon, D., Mueller, H. J., Bardins, S., & Makeig, S. (2010). Human brain dynamics accompanying use of egocentric and allocentric reference frames during navigation. Journal of Cognitive Neuroscience, 22(12), 2836–2849. doi: 10.1162/jocn.2009.21369.CrossRefGoogle ScholarPubMed
Han, S., Lu, Y., Xie, J., Fei, Y., Zheng, G., Wang, Z., … Li, L. (2021). Probiotic gastrointestinal transit and colonization after oral administration: A long journey. Frontiers in Cellular and Infection Microbiology, 11, 609722. doi: 10.3389/fcimb.2021.609722.CrossRefGoogle ScholarPubMed
Hautzinger, M., Keller, F., & Kühner, C. (2006). Beck depressions-inventar (BDI-II). Göttingen: Hogrefe.Google Scholar
Henry, L. P., Bruijning, M., Forsberg, S. K. G., & Ayroles, J. F. (2021). The microbiome extends host evolutionary potential. Nature Communications, 12(1), 5141. doi: 10.1038/s41467-021-25315-x.CrossRefGoogle ScholarPubMed
Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., … Sanders, M. E. (2014). The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, 11(8), 506–514. doi: 10.1038/nrgastro.2014.66.CrossRefGoogle ScholarPubMed
Jäger, A. O., Süß, H.-M., & Beauducel, A. (1997). Berliner intelligenzstruktur-test: BIS-test [Berlin Intelligence Structure Test: BIS-Test]. Göttingen: Hogrefe.Google Scholar
Kessels, R. P. C., van Zandvoort, M. J. E., Postma, A., Kappelle, L. J., & de Haan, L. J. (2000). The corsi block-tapping task: Standardization and normative data. Applied Neuropsychology, 7(4), 252–258. doi: 10.1207/S15324826AN0704_8.CrossRefGoogle ScholarPubMed
Klein, E. M., Brähler, E., Dreier, M., Reinecke, L., Müller, K. W., Schmutzer, G., … Beutel, M. E. (2016). The German version of the perceived stress scale – Psychometric characteristics in a representative German community sample. BMC Psychiatry, 16(1), 159. doi: 10.1186/s12888-016-0875-9.CrossRefGoogle Scholar
Kühner, C., Huffziger, S., & Nolen-Hoeksema, S. (2016). RSQ-D: Response style questionnaire – deutsche version [RSQ-D: Response Style Questionnaire – German version]. Göttingen: Hogrefe.Google Scholar
Lang, U. E., Hellweg, R., & Gallinat, J. (2004). BDNF Serum concentrations in healthy volunteers are associated with depression-related personality traits. Neuropsychopharmacology, 29(4), 795–798. doi: 10.1038/sj.npp.1300382.CrossRefGoogle ScholarPubMed
Lv, T., Ye, M., Luo, F., Hu, B., Wang, A., Chen, J., … Ding, Z. (2021). Probiotics treatment improves cognitive impairment in patients and animals: A systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 120, 159–172. doi: 10.1016/j.neubiorev.2020.10.027.CrossRefGoogle ScholarPubMed
Marttinen, M., Ala-Jaakkola, R., Laitila, A., & Lehtinen, M. J. (2020). Gut microbiota, probiotics and physical performance in athletes and physically active individuals. Nutrients, 12(10), 2936. doi: 10.3390/nu12102936.CrossRefGoogle ScholarPubMed
Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F., & Tillisch, K. (2014). Gut microbes and the brain: Paradigm shift in neuroscience. Journal of Neuroscience, 34(46), 15490–15496. doi: 10.1523/JNEUROSCI.3299-14.2014.CrossRefGoogle ScholarPubMed
Mohammadi, G., Dargahi, L., Naserpour, T., Mirzanejad, Y., Alizadeh, S. A., Peymani, A., & Nassiri-Asl, M. (2019). Probiotic mixture of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 attenuates hippocampal apoptosis induced by lipopolysaccharide in rats. International Microbiology, 22(3), 317–323. doi: 10.1007/s10123-018-00051-3.CrossRefGoogle ScholarPubMed
Möhle, L., Mattei, D., Heimesaat, M. M., Bereswill, S., Fischer, A., Alutis, M., … Wolf, S. A. (2016). Ly6Chi monocytes provide a link between antibiotic-induced changes in gut microbiota and adult hippocampal neurogenesis. Cell Reports, 15(9), 1945–1956. doi: 10.1016/j.celrep.2016.04.074.CrossRefGoogle ScholarPubMed
Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021). The gut microbiota–brain axis in behaviour and brain disorders. Nature Reviews Microbiology, 19(4), 241–255. doi: 10.1038/s41579-020-00460-0.CrossRefGoogle ScholarPubMed
Morey, R. A., Petty, C. M., Xu, Y., Hayes, J. P., Wagner, H. R., Lewis, D. V., … McCarthy, G. (2009). A comparison of automated segmentation and manual tracing for quantifying hippocampal and amygdala volumes. NeuroImage, 45(3), 855–866. doi: 10.1016/j.neuroimage.2008.12.033.CrossRefGoogle ScholarPubMed
Nolen-Hoeksema, S. (1991). Responses to depression and their effects on the duration of depressive episodes. Journal of Abnormal Psychology, 100(4), 569–582. doi: 10.1037//0021-843x.100.4.569.CrossRefGoogle ScholarPubMed
O'Hagan, C., Li, J. V., Marchesi, J. R., Plummer, S., Garaiova, I., & Good, M. A. (2017). Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats. Neurobiology of Learning and Memory, 144, 36–47. doi: 10.1016/j.nlm.2017.05.015.CrossRefGoogle ScholarPubMed
Papalini, S., Michels, F., Kohn, N., Wegman, J., van Hemert, S., Roelofs, K., … Aarts, E. (2019). Stress matters: Randomized controlled trial on the effect of probiotics on neurocognition. Neurobiology of Stress, 10, 100141. doi: 10.1016/j.ynstr.2018.100141.CrossRefGoogle ScholarPubMed
Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage, 59(3), 2142–2154. doi: 10.1016/j.neuroimage.2011.10.018.CrossRefGoogle ScholarPubMed
Rahmati, H., Momenabadi, S., Vafaei, A. A., Bandegi, A. R., Mazaheri, Z., & Vakili, A. (2019). Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model. Molecular Biology Reports, 46(5), 4985–4995. doi: 10.1007/s11033-019-04949-7.CrossRefGoogle Scholar
Schmiedek, F., Lövdén, M., & Lindenberger, U. (2010). Hundred days of cognitive training enhance broad cognitive abilities in adulthood: Findings from the COGITO study. Frontiers in Aging Neuroscience, 13(2), 27. doi: 10.3389/fnagi.2010.00027.Google Scholar
Sender, R., Fuchs, S., & Milo, R. (2016). Revised estimates for the number of human and bacteria cells in the body. PLoS Biology, 14(8), e1002533. doi: 10.1371/journal.pbio.1002533.CrossRefGoogle ScholarPubMed
Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. C. (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. The Journal of Clinical Psychiatry, 59(Suppl. 20), 22–33; quiz 34–57. Retrieved from https://pubmed.ncbi.nlm.nih.gov/9881538/.Google ScholarPubMed
Shori, A. B. (2017). Microencapsulation improved probiotics survival during gastric transit. HAYATI Journal of Biosciences, 24(1), 1–5. doi: 10.1016/j.hjb.2016.12.008.CrossRefGoogle Scholar
Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A. (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature, 476(7361), 458–461. doi: 10.1038/nature10287.CrossRefGoogle ScholarPubMed
Tang, W., Meng, Z., Li, N., Liu, Y., Li, L., Chen, D., & Yang, Y. (2021). Roles of gut microbiota in the regulation of hippocampal plasticity, inflammation, and hippocampus-dependent behaviors. Frontiers in Cellular and Infection Microbiology, 10, 611014. doi: 10.3389/fcimb.2020.611014.CrossRefGoogle ScholarPubMed
Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., … Mayer, E. A. (2013). Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology, 144(7), 1394–1401.e4. doi: 10.1053/j.gastro.2013.02.043.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., … Joliot, M. (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage, 15(1), 273–289. doi: 10.1006/nimg.2001.0978.CrossRefGoogle ScholarPubMed
van Doorn, J., van den Bergh, D., Böhm, U., Dablander, F., Derks, K., Draws, T., … Wagenmakers, E.-J. (2020). The JASP guidelines for conducting and reporting a Bayesian analysis. Psychonomic Bulletin & Review, 28, 813–826. doi: 10.3758/s13423-020-01798-5.CrossRefGoogle Scholar
Wang, H., Braun, C., Murphy, E. F., & Enck, P. (2019). Bifidobacterium longum 1714™ strain modulates brain activity of healthy volunteers during social stress. The American Journal of Gastroenterology, 114(7), 1152–1162. doi: 10.14309/ajg.0000000000000203.CrossRefGoogle ScholarPubMed
Wang, Y., Jiang, Y., Deng, Y., Yi, C., Wang, Y., Ding, M., … Wong, A. (2020). Probiotic supplements: Hope or hype? Frontiers in Microbiology, 11, 160. doi: 10.3389/fmicb.2020.00160.CrossRefGoogle ScholarPubMed
Wilckens, K. A., Stillman, C. M., Waiwood, A. M., Kang, C., Leckie, R. L., Peven, J. C., … Erickson, K. I. (2021). Exercise interventions preserve hippocampal volume: A meta-analysis. Hippocampus, 31(3), 335–347. doi: 10.1002/hipo.23292.CrossRefGoogle ScholarPubMed
Wilson, B., Cockburn, J., Baddeley, A., & Hiorns, R. (1989). The development and validation of a test battery for detecting and monitoring everyday memory problems. Journal of Clinical and Experimental Neuropsychology, 11(6), 855–870. doi: 10.1080/01688638908400940.CrossRefGoogle ScholarPubMed
Yushkevich, P. A., Wang, H., Pluta, J., Das, S. R., Craige, C., Avants, B. B., … Mueller, S. (2010). Nearly automatic segmentation of hippocampal subfields in in vivo focal T2-weighted MRI. NeuroImage, 53(4), 208–224. doi: 10.1016/j.neuroimage.2010.06.040.CrossRefGoogle ScholarPubMed
Yushkevich, P. A., Wolk, D., Pluta, J., & Ding, S. L. (2016). UPenn PMC Atlas – 2016 Version. Retrieved from https://www.nitrc.org/frs/shownotes.php?release_id=3453.Google Scholar
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