Effects of mesalamine (5-aminosalicylic acid) on bacterial gene expression
Bibliographic record
Abstract
BACKGROUND: 5-Aminosalicylic acid (5-ASA) is a well-established treatment for inflammatory bowel disease (IBD) and may reduce the risk of colon cancer in patients with chronic colitis, but the mechanisms underlying these effects have not been fully elucidated. Although 5-ASA delivery is targeted to the distal gut, little is known about its effects on the luminal bacteria that reside there. Intestinal bacteria are believed play a role in causing or perpetuating IBD, and bioremediation has been studied as a therapeutic strategy. In an effort to better understand the bacteriological effects of 5-ASA, we examined the role of this compound at the level of bacterial gene expression. METHODS: 5-ASA was screened for its effects on a random promoter library representing the genome of Salmonella enterica serovar Typhimurium as a model enteric bacterium. Forty-five constructs representing 38 unique promoters were found to be responsive to 5-ASA, and included genes involved in bacterial invasion, cellular metabolism, and stress resistance. Several genes of unknown function were also identified. These effects occurred at 5-ASA concentrations that are relevant to those achieved in the distal intestinal tract in patients with IBD but did not inhibit bacterial growth. RESULTS: Bacterial invasiveness was decreased by 5-ASA. Some of the identified genes had homologs among commensal Gram-negative enteric bacteria. CONCLUSIONS: This study demonstrates that 5-ASA has potent effects on bacterial gene expression. These novel findings implicate intestinal bacteria as pharmacological targets of 5-ASA, perhaps contributing to the therapeutic action of this important class of IBD drugs.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".