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Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer's Disease
Lukiw WJ.. Frontiers in microbiology, 2016-09-26
Topic: Gut, metabolism and diet
Plain-language summary
The human microbiome consists of ~3.8 × 10 13 symbiotic microorganisms that form a highly complex and dynamic ecosystem: the gastrointestinal (GI) tract constitutes the largest repository of the human microbiome by far, and its impact on human neurological health and disease is becoming increasingly appreciated. Bacteroidetes, the largest phylum of Gram-negative bacteria in the GI tract microbiome, while generally beneficial to the host when confined to the GI tract, have potential to secrete a remarkably complex array of pro-inflammatory neurotoxins that include surface lipopolysaccharides (LPSs) and toxic proteolytic peptides. The deleterious effects of these bacterial exudates appear to become more important as GI tract and blood-brain barriers alter or increase their permeability with aging and disease. For example, presence of the unique LPSs of the abundant Bacteroidetes species Bacteroides fragilis (BF-LPS) in the serum represents a major contributing factor to systemic inflammation. BF-LPS is further recognized by TLR2, TLR4, and/or CD14 microglial cell receptors as are the pro-inflammatory 42 amino acid amyloid-beta (Aβ42) peptides that characterize Alzheimer's disease (AD) brain. Here we provide the first evidence that BF-LPS exposure to human primary brain cells is an exceptionally potent inducer of the pro-inflammatory transcription factor NF-kB (p50/p65) complex, a known trigger in the expression of pathogenic pathways involved in inflammatory neurodegeneration. This 'Perspectives communication' will in addition highlight work from recent studies that advance novel and emerging concepts on the potential contribution of microbiome-generated factors, such as BF-LPS, in driving pro-inflammatory degenerative neuropathology in the AD brain.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lukiw, W. J. (2016). Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer's Disease. Frontiers in microbiology. https://doi.org/10.3389/fmicb.2016.01544
Vancouver
Lukiw WJ. Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer's Disease. Frontiers in microbiology. 2016. doi:10.3389/fmicb.2016.01544. PMID: 27725817.
BibTeX
@article{lukiw2016-27725817,
author = {Lukiw, W. J.},
title = {{Bacteroides fragilis Lipopolysaccharide and Inflammatory Signaling in Alzheimer's Disease}},
journal = {Frontiers in microbiology},
year = {2016},
doi = {10.3389/fmicb.2016.01544},
pmid = {27725817},
url = {https://doi.org/10.3389/fmicb.2016.01544}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- The deleterious effects of these bacterial exudates appear to become more important as GI tract and blood-brain barriers alter or increase their permeability with aging and disease.
- For example, presence of the unique LPSs of the abundant Bacteroidetes species Bacteroides fragilis (BF-LPS) in the serum represents a major contributing factor to systemic inflammation.
- BF-LPS is further recognized by TLR2, TLR4, and/or CD14 microglial cell receptors as are the pro-inflammatory 42 amino acid amyloid-beta (Aβ42) peptides that characterize Alzheimer's disease (AD) brain.
- Here we provide the first evidence that BF-LPS exposure to human primary brain cells is an exceptionally potent inducer of the pro-inflammatory transcription factor NF-kB (p50/p65) complex, a known trigger in the expression of pathogenic pathways involved in inflammatory neurodegeneration.
- This 'Perspectives communication' will in addition highlight work from recent studies that advance novel and emerging concepts on the potential contribution of microbiome-generated factors, such as BF-LPS, in driving pro-inflammatory degenerative neuropathology in the AD brain.
Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 multicenter collaboration, so those were left out: it earned 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in microbiology) |
| 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 | 1 / 5 | 2016 — within 20 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 | — / 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27725817) |
| Free to read | 2 / 2 | Free to read |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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