Skip to main content Accessibility help

Increasing reproducibility and interpretability of microbiota-gut-brain studies on human neurocognition and intermediary microbial metabolites

  • Esther Aarts (a1) and Sahar El Aidy (a2)


In this commentary, we point to guidelines for performing human neuroimaging studies and their reporting in microbiota-gut-brain (MGB) articles. Moreover, we provide a view on interpretational issues in MGB studies, with a specific focus on gut microbiota–derived metabolites. Thus, extending the target article, we provide recommendations to the field to increase reproducibility and relevance of this type of MGB study.



Hide All
Aarts, E., Ederveen, T. H. A., Naaijen, J., Zwiers, M. P., Boekhorst, J., Timmerman, H. M., Smeekens, S. P., Netea, M. G., Buitelaar, J. K., Franke, B., van Hijum, S. A. F. T. & Arias Vasquez, A. (2017) Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS ONE 12(9):e0183509. Available at:
Adair, K. L. & Douglas, A. E. (2017) Making a microbiome: The many determinants of host-associated microbial community composition. Current Opinion in Microbiology 35:2329. Available at:
Ahluwalia, V., Wade, J. B., Heuman, D. M., Hammeke, T. A., Sanyal, A. J., Sterling, R. K., Stravitz, R. T., Luketic, V., Siddiqui, M. S., Puri, P., Fuchs, M., Lennon, M. J., Kraft, K. A., Gilles, H., White, M. B., Noble, N. A. & Bajaj, J. S. (2014) Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with rifaximin in cirrhosis: Implications for the gut-liver-brain axis. Metabolic Brain Disease 29(4):1017–25. Available at:
Bagga, D., Aigner, C. S., Reichert, J. L., Cecchetto, C., Fischmeister, F. P. S., Holzer, P., Moissl-Eichinger, C. & Schöpf, V. (2018a) Influence of 4-week multi-strain probiotic administration on resting-state functional connectivity in healthy volunteers. European Journal of Nutrition. Available at:
Bagga, D., Reichert, J. L., Koschutnig, K., Aigner, C. S., Holzer, P., Koskinen, K., Moissl-Eichinger, C. & Schopf, V. (2018b) Probiotics drive gut microbiome triggering emotional brain signatures. Gut Microbes 9(6):486–96. Available at:
Chambers, C. D., Feredoes, E., Muthukumaraswamy, S. D. & Etchells, P. J. (2014) Instead of “playing the game” it is time to change the rules: Registered Reports at AIMS Neuroscience and beyond. AIMS Neuroscience 1(1):417.
Dutta, D., Heo, I. & Clevers, H. (2017) Disease modeling in stem cell-derived 3D organoid systems. Trends in Molecular Medicine 23(5):393410. Available at:
Editorial (2017) Overcoming hurdles in sharing microbiome data. Nature Microbiology 2(12):1573. Available at:
Eklund, A., Nichols, T. E. & Knutsson, H. (2016) Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences USA 113(28):7900–905. Available at:
Forstmeier, W., Wagenmakers, E. J. & Parker, T. H. (2017) Detecting and avoiding likely false-positive findings: A practical guide. Biological Reviews: Cambridge Philosophical Society 92(4):1941–68. Available at:
Lagier, J. C., Dubourg, G., Million, M., Cadoret, F., Bilen, M., Fenollar, F., Levasseur, A., Rolain, J.-M., Fournier, P.-E. & Raoult, D. (2018) Culturing the human microbiota and culturomics. Nature Reviews Microbiology 16:540–50. Available at:
Nichols, T. E., Das, S., Eickhoff, S. B., Evans, A. C., Glatard, T., Hanke, M., Kriegeskorte, N., Milham, M. P., Poldrack, R. A., Poline, J.-B., Proal, E., Thirion, B., Van Essen, D. C., White, T. & Yeo, B. T. (2017) Best practices in data analysis and sharing in neuroimaging using MRI. Nature Neuroscience 20(3):299303. Available at:
Osadchiy, V., Labus, J. S., Gupta, A., Jacobs, J., Ashe-McNalley, C., Hsiao, E. Y. & Mayer, E. A. (2018) Correlation of tryptophan metabolites with connectivity of extended central reward network in healthy subjects. PLoS ONE 13(8):e0201772. Available at:
Pinto-Sanchez, M. I., Hall, G. B., Ghajar, K., Nardelli, A., Bolino, C., Lau, J. T., Martin, F.-P., Cominetti, O., Welsh, C., Rieder, A., Traynor, J., Gregory, C., De Palma, G., Pigrau, M., Ford, A. C., Macri, J., Berger, B., Bergonzelli, G. & Bercik, P. (2017) Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: A pilot study in patients with irritable bowel syndrome. Gastroenterology 153(2):448–59.e8. Available at:
Poldrack, R. A., Fletcher, P. C., Henson, R. N., Worsley, K. J., Brett, M. & Nichols, T. E. (2008) Guidelines for reporting an fMRI study. Neuroimage 40(2):409–14.
Postler, T. S. & Ghosh, S. (2017) Understanding the holobiont: How microbial metabolites affect human health and shape the immune system. Cell Metabolism 26(1):110–30. Available at:
Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., Guyonnet, D., Legrain-Raspaud, S., Trotin, B., Naliboff, B. & Mayer, E.A. (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144(7):1394–401.
Tillisch, K., Mayer, E. A., Gupta, A., Gill, Z., Brazeilles, R., Le Nevé, B., van Hylckama Vlieg, J. E. T., Guyonnet, D., Derrien, M. & Labus, J. S. (2017) Brain structure and response to emotional stimuli as related to gut microbial profiles in healthy women. Psychosomatic Medicine 79(8):905–13. Available at:
Waclawikova, B. & El Aidy, S. (2018) Role of microbiota and tryptophan metabolites in the remote effect of intestinal inflammation on brain and depression. Pharmaceuticals (Basel) 11(3):63. Available at:

Increasing reproducibility and interpretability of microbiota-gut-brain studies on human neurocognition and intermediary microbial metabolites

  • Esther Aarts (a1) and Sahar El Aidy (a2)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed