Gut microbiome and magnetic resonance spectroscopy study of subjects at ultra-high risk for psychosis may support the membrane hypothesis
Open accessAbstract
Background: The microbiota-gut-brain axis and membrane dysfunction in the brain has attracted increasing attention in the field of psychiatric research. However, the possible interactive role of gut microbiota and brain function in the prodromal stage of schizophrenia has not been studied yet. Methods: To explore this, we collected fecal samples and performed Magnetic Resonance Spectroscopy (MRS) scans in 81 high risk (HR) subjects, 19 ultra-high risk (UHR) subjects and 69 health controls (HC). Then we analyzed the differences in gut microbiota and choline concentrations in the anterior cingulate cortex (ACC). Results: Presences of the orders Clostridiales,Lactobacillales and Bacteroidales were observed at increase levels in fecal samples of UHR subjects compared to the other two groups. The composition changes of gut microbiota indicate the increased production of Short Chain Fatty Acids (SCFAs), which could activate microglia and then disrupt membrane metabolism. Furthermore, this was confirmed by an increase of choline levels, a brain imaging marker of membrane dysfunction, which is also significantly elevated in UHR subjects compared to the HR and HC groups. Conclusion: Both gut microbiome and imaging studies of UHR subjects suggest the membrane dysfunction in the brain and hence might support the membrane hypothesis of schizophrenia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Gut microbiome composition and metabolome are altered in many brain disorders.
“Interestingly, several studies have found that the gut microbiome composition and, consequently, metabolome are altered in many brain disorders (138–142).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [141]
Cites
Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences
Langille, M. G. I., Zaneveld, J., Caporaso, J. G., McDonald, D., Knights, D., Reyes, J. A., Clemente, J. C., Burkepile, D. E., Vega Thurber, R. L., Knight, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2676 · Cited by 9,116 · see citing works
Self-citationRevised Estimates for the Number of Human and Bacteria Cells in the Body
Sender, R., Fuchs, S., & Milo, R. (2016) · PLOS Biology · doi:10.1371/journal.pbio.1002533 · Cited by 5,425 · see citing works
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244 · see citing works
The impact of the gut microbiota on human health: an integrative view
Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012) · Cell · doi:10.1016/j.cell.2012.01.035 · Cited by 3,710 · see citing works
Self-citationPrinciples and clinical implications of the brain-gut-enteric microbiota axis
Rhee, S. H., Pothoulakis, C., & Mayer, E. A. (2009) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.35 · Cited by 1,342 · cited 1× · see citing works
“The concept of the microbiota-gut-brain axis was proposed nearly a decade ago [8].”
BackgroundStrains, functions and dynamics in the expanded Human Microbiome Project
Lloyd-Price, J., Mahurkar, A., Rahnavard, G., Crabtree, J., Orvis, J., Hall, A. B., Brady, A., Creasy, H. H., McCracken, C., Giglio, M. G., et al. (2017) · Nature · doi:10.1038/nature23889 · Cited by 1,267 · see citing works
Self-citationMicroglia and neuroinflammation: a pathological perspective
Streit (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-14 · Cited by 1,039 · see citing works
The impact of microglial activation on blood-brain barrier in brain diseases
da Fonseca, A. C. C., Matias, D., Garcia, C., Amaral, R., Geraldo, L. H., Freitas, C., & Lima, F. R. S. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00362 · Cited by 572 · see citing works
Schwarz, E., Maukonen, J., Hyytiäinen, T., Kieseppä, T., Orešič, M., Sabunciyan, S., Mantere, O., Saarela, M., Yolken, R., & Suvisaari, J. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2017.04.017 · Cited by 333 · see citing works
Evidence for activation of microglia in patients with psychiatric illnesses
Bayer, T. A., Buslei, R., Havas, L., & Falkai, P. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00545-5 · Cited by 323 · see citing works
Cordes, J. S., Mathiak, K. A., Dyck, M., Alawi, E. M., Gaber, T. J., Zepf, F. D., Klasen, M., Zvyagintsev, M., Gur, R. C., & Mathiak, K. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00169 · Cited by 69 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · see citing works
“Contrarily, a microbiome study in schizophrenic patients at risk of developing psychosis reported enriched Clostridiales, Prevotella, and Lactobacillus ruminis and predicted increased SCFA production (141).”
BackgroundThe Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders
Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J., & Wlaź, P. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105840 · Cited by 857 · see citing works
Sun, J., Xu, J., Ling, Y., Wang, F., Gong, T., Yang, C., Ye, S., Ye, K., Wei, D., Song, Z., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0525-3 · Cited by 532 · see citing works
Nguyen, T. T., Kosciolek, T., Maldonado, Y., Daly, R. E., Martin, A. S., McDonald, D., Knight, R., & Jeste, D. V. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2018.09.014 · Cited by 260 · see citing works
Self-citationAltered gut microbiota associated with symptom severity in schizophrenia
Li, S., Zhuo, M., Huang, X., Huang, Y., Zhou, J., Xiong, D., Li, J., Liu, Y., Pan, Z., Li, H., et al. (2020) · PeerJ · doi:10.7717/peerj.9574 · Cited by 142 · see citing works
Okubo, R., Koga, M., Katsumata, N., Odamaki, T., Matsuyama, S., Oka, M., Narita, H., Hashimoto, N., Kusumi, I., Xiao, J., et al. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.11.011 · Cited by 149 · see citing works
Spichak, S., Bastiaanssen, T. F. S., Berding, K., Vlckova, K., Clarke, G., Dinan, T. G., & Cryan, J. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.044 · Cited by 127 · see citing works
Ma, X., Asif, H., Dai, L., He, Y., Zheng, W., Wang, D., Ren, H., Tang, J., Li, C., Jin, K., et al. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.02.005 · Cited by 114 · see citing works
Self-citationMinichino, A., Brondino, N., Solmi, M., Del Giovane, C., Fusar-Poli, P., Burnet, P., Cipriani, A., & Lennox, B. R. (2021) · Schizophrenia Research · doi:10.1016/j.schres.2020.02.012 · Cited by 50 · see citing works
- Authors
- He, Y., Kosciolek, T., Tang, J., Zhou, Y., Li, Z., Ma, X., Zhu, Q., Yuan, N., Yuan, L., Li, C., Jin, K., Knight, R., Tsuang, M. T., & Chen, X.
- Affiliations
- Central South University (CN)
- University of California San Diego (US)
- Hunan Children's Hospital (CN)
- Harvard University (US)
- Corresponding author
- Chen, Xiaogang
- ORCID
- Venue
- European Psychiatry
- Publisher
- Cambridge University Press (CUP)
- Published
- 2018-06-02
- Volume
- 53
- Pages
- 37-45
- ISSN
- 0924-9338 (ISSN-L)
- 1778-3585
- OpenAlex
- W2805843535
- Cited by
- 123
- References
- 11
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 26 · 2021: 16 · 2020: 18 · 2019: 13 · 2018: 5
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81471361, 81271484)
- China Scholarship Council (201606370199)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- gut microbiota, clinical high risk for psychosis, prodromal schizophrenia, microbiota-gut-brain axis, choline, anterior cingulate cortex, short-chain fatty acids, microglial activation, membrane dysfunction, Clostridiales, Lactobacillales, Bacteroidales, fecal microbiota
- MeSH terms
- Gastrointestinal Microbiome, Adolescent, Adult, Choline, Female, Gyrus Cinguli, Humans, Male, Magnetic Resonance Spectroscopy, Psychotic Disorders, Schizophrenia, Young Adult, Neuroimaging, Prodromal Symptoms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review