A5 FRUCTOOLIGOSACCHARIDE EXACERBATES INFLAMMATION AND THE LOSS OF MICROBIAL DIVERSITY FOLLOWING ILEOCECAL RESECTION IN A MURINE MODEL OF POST-OPERATIVE CROHN’S DISEASE RECURRENCE
Bibliographic record
Abstract
Fructooligosaccharide (FOS) is a fermentable prebiotic that stimulates the growth of bifidobacteria which has been shown to have anti-inflammatory activity. Individuals with Crohn’s disease frequently require ileocolic resection (ICR), and disease often recurs in the neo-terminal ileum following surgery. Previously we have shown that ICR in a mouse model induces gut dysbiosis, a depletion of anaerobic microbes, including bifidobacteria, and an increase in ileal inflammation. We hypothesized supplementation of a post-ICR diet with FOS in a mouse model would be effective in stimulating the growth of bifidobacteria and thus reducing systemic and local inflammation. ICR was performed in IL10-/- mice (129S1/SvlmJ) with established colitis. Following surgery, mice were subsequently fed a chow diet ± 10% FOS for 28 days (n=11), alongside diet-matched non-ICR control groups (n=11). Serum, colon, and terminal ileum (TI) were analyzed for cytokine expression by a MesoScale discovery platform. DNA extracted from stool was analyzed using 16s rRNA sequencing and qPCR. Expression of tight junction genes occludin and ZO1 was assessed using qPCR. Short-chain fatty acids (SCFA) concentrations were assessed using high-pressure liquid chromatography. A precipitous decrease in fecal bifidobacteria and bacterial diversity was seen following ICR (p<0.05). ICR also led to increased serum inflammatory cytokines (IL-2, IL-12, IL-4) (p<0.05) and a complete depletion of fecal butyrate (p<0.01). FOS-supplementation resulted in an increase in the relative amount of bifidobacteria and fecal acetate (p<0.01). However, contrary to our hypothesis, the FOS diet exacerbated post-operative systemic inflammation (elevated serum IL-6 p<0.05), ileitis (elevated IL-1β p<0.1) and colitis (elevated IFNγ and TNFα p<0.05). FOS-supplementation was not able to reverse the obliteration of fecal butyrate following ICR. Expression of occludin and ZO1 was reduced in FOS-supplemented mice (p<0.05). FOS supplementation exacerbated the loss of bacterial diversity following ICR and there was a correlation between loss of diversity and bifidogenic effectiveness of FOS in promoting bifidobacteria growth (r= -0.61, p<0.05). FOS-supplementation of a post-ICR diet resulted in a decrease in fecal bacterial diversity, reduction in barrier function, and increased inflammation. We speculate that providing high amounts of a targeted substrate allowed for the expansion of bifidobacteria’s niche, enabling a bloom of acetate-producing organisms which consequently hindered the growth of butyrate–producing anaerobic organisms necessary for gut homeostasis. None
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".