Cerebrospinal fluid microbiome revisited: no evidence of resident bacteria in archived samples
Bibliographic record
Abstract
ABSTRACT DNA from oral bacteria has been detected in the cerebrospinal fluid (CSF) of patients with Alzheimer’s disease and related dementias (AD/ADRD). We hypothesized that examination of archived CSF samples from donors with variable cognitive status would reveal evidence of a resident microbiome. 176 CSF samples harvested from community-dwelling individuals (77% between 61 and 80 years old) were analyzed; 57% originated from donors with impaired cognitive status. DNA was extracted after adding microbial spike-in controls, and libraries were prepared and sequenced on an Illumina-MiSeq platform. 16S rRNA sequences were processed, and a taxonomic classification was performed. Spike-in bacteria were consistently detected, and Streptococcus pneumoniae was found in a positive control sample from a patient with bacterial meningitis. However, very few reads mapping to other bacterial taxa were detected across samples, suggesting a negligible bacterial content consistent with occasional contamination or sequencing errors. CSF is a privileged, sterile environment that does not harbor a resident microbiome in elderly people with various morbidities, including AD/ADRD. IMPORTANCE Recent reports have suggested that DNA from oral bacteria has been found in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease and related dementias (AD/ADRD). We hypothesized that examination of archived CSF samples from donors with variable cognitive status would reveal evidence of a resident microbiome. We thus analyzed 176 CSF samples harvested from community-dwelling individuals including donors with impaired cognitive status. While our findings suggested the presence of occasional bacterial contamination, they provided no evidence of a resident microbiome. We thus conclude that the CSF is indeed a privileged, sterile environment that does not harbor a resident microbiome in elderly people with various morbidities including AD/ADRD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.008 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".