A42 A HIGH SALT DIET INCREASES ELASTOLYTIC ACTIVITY AND WORSENS COLITIS IN GNOTOBIOTIC MICE
Bibliographic record
Abstract
Abstract Background Recent evidence has linked ultra-processed foods, which are high in salt, to increased risk of inflammatory bowel disease (IBD). A high salt diet (HSD) was also shown to be colitogenic in specific pathogen-free mice, in part, through modulation of the microbiota. We recently described high microbial proteolytic activity (PA) in feces from IBD patients, that when transferred to germ-free mice, increased acute colitis severity. However, the drivers of high microbial PA are unknown. Aims To determine whether HSD increases proteolytic activity, thereby exacerbating colitis. Methods Adult germ-free (GF) C57BL/6 mice were colonized with feces from a patient with UC in flare (n=13). Mice were fed either a control diet (CD; 7004, Teklad) or a HSD (7004 supplemented with 4% NaCl) plus 1% NaCl in drinking water. Three weeks following colonization, chronic colitis was induced in half of the mice by three cycles (five days each; 2.0%, 1.5% and 1.5%, respectively) of DSS in drinking water with a five-day wash-out period between cycles. Fecal PA and predicted microbial protease profiles were measured before colitis induction. Weight loss and disease activity (e.g., occult blood in feces and stool consistency) was evaluated for the duration of colitis and microscopic colitis was evaluated at endpoint. Results In mice colonized with UC microbiota, a HSD increased elastolytic activity (p=.03 versus CD) and induced a unique predicted protease and peptidase profile. After colitis induction, mice consuming a HSD lost more weight than mice consuming the CD (p=.0001) and had higher disease activity (p=.0004). Additionally, HSD induced more severe microscopic colitis scores compared with the CD (p=.0001). Conclusions These results raise the hypothesis that a HSD drives microbial proteolytic activity of IBD microbiota. However, whether this shift is causally associated with the worsening of colitis remains unclear. Mechanistic insight underlying this HSD-microbial proteolytic function could lead to specific dietary modifications or anti-proteolytic therapies for IBD in patients with proteolytic-driven inflammation. Funding Agencies CCC, CIHR
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".