Home › Research › Caregiving
C9orf72 suppresses systemic and neural inflammation induced by gut bacteria
Burberry A, Wells MF, Limone F, Couto A, Smith KS, Keaney J, Gillet G, van Gastel N et al.. Nature, 2020-05-13
Topic: Brain proteins, microglia and lab models
A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia 1,2 . The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration 3-9 . The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins 5 before its non-canonical translation into neural-toxic dipeptide proteins 3,4 . The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation 6-9 . Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria 10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Burberry, A., Wells, M. F., Limone, F., Couto, A., Smith, K. S., Keaney, J., et al. (2020). C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature. https://doi.org/10.1038/s41586-020-2288-7
Vancouver
Burberry A, Wells MF, Limone F, Couto A, Smith KS, Keaney J, et al. C9orf72 suppresses systemic and neural inflammation induced by gut bacteria. Nature. 2020. doi:10.1038/s41586-020-2288-7. PMID: 32483373.
BibTeX
@article{burberry2020-32483373,
author = {Burberry, A. and Wells, M. F. and Limone, F. and Couto, A. and Smith, K. S. and Keaney, J. and Gillet, G. and van Gastel, N. and others},
title = {{C9orf72 suppresses systemic and neural inflammation induced by gut bacteria}},
journal = {Nature},
year = {2020},
doi = {10.1038/s41586-020-2288-7},
pmid = {32483373},
url = {https://doi.org/10.1038/s41586-020-2288-7}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Here we report that an environment with reduced abundance of immune-stimulating bacteria 10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity.
- Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset.
Why it matters
In C9orf72-mutant mice, reducing immune-stimulating gut bacteria protected against premature mortality and ameliorated systemic inflammation and autoimmunity. This is an animal study relevant to amyotrophic lateral sclerosis and frontotemporal dementia, not a demonstrated treatment, cure, or prevention for Alzheimer's disease.
New to this subject? Start with our plain-English guide: Caregiving →
Study details
- Evidence strengthLow
How this study scored 56/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (OpenAlex, 2026-10-29) |
| 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 314 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 39.2 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 5 / 6 | Cited 20.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 3 / 4 | Cited 110 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Kevin C. Eggan: h-index 75 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32483373) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 13.
Later studies that cite this one
2 studies in the alzhub library list this one in their references.
Related studies in Caregiving
Also tagged “tdp-43”
1,150 studies in the library carry the topic tag “tdp-43”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.