Topic: Gut, metabolism and diet
Background Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer's disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ). Methods A two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively. Results We found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79-0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92-1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00-1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83-0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00-1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02-1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition. Conclusions These data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.
Key findings
- Background Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions.
- Results We found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79-0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92-1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD.
- Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00-1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83-0.98; P = 0.011) was related to a lower risk for SCZ.
- Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00-1.15; P = 0.047).
- Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02-1.12; P = 0.010).
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuroinflammation) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33008395) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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APA 7th
Zhuang, Z., Yang, R., Wang, W., Qi, L., & Huang, T. (2020). Associations between gut microbiota and Alzheimer's disease, major depressive disorder, and schizophrenia. Journal of neuroinflammation. https://doi.org/10.1186/s12974-020-01961-8
Vancouver
Zhuang Z, Yang R, Wang W, Qi L, Huang T. Associations between gut microbiota and Alzheimer's disease, major depressive disorder, and schizophrenia. Journal of neuroinflammation. 2020. doi:10.1186/s12974-020-01961-8. PMID: 33008395.
BibTeX
@article{zhuang2020-33008395,
author = {Zhuang, Z. and Yang, R. and Wang, W. and Qi, L. and Huang, T.},
title = {{Associations between gut microbiota and Alzheimer's disease, major depressive disorder, and schizophrenia}},
journal = {Journal of neuroinflammation},
year = {2020},
doi = {10.1186/s12974-020-01961-8},
pmid = {33008395},
url = {https://doi.org/10.1186/s12974-020-01961-8}
}
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