A230 ISOMALTODEXTRIN DOSE-DEPENDENTLY REDUCES COLITIS DEVELOPMENT IN HLA-B27 RAT COLITIS MODEL WITH ASSOCIATED CHANGES TO GUT MICROBIOME COMPOSITION AND SHORT CHAIN FATTY ACID PRODUCTION
Bibliographic record
Abstract
Abstract Background Inflammatory bowel disease (IBD) is characterized by altered intestinal microbiome (i.e. dysbiosis), described by reduced strict butyrate-producing anaerobes versus increased facultative anaerobes. Data from preclinical studies and clinical trials show prebiotic inulin-type fibers can prevent and reduce colitis. However, other dietary fibers (e.g. resistant starches, RS) are understudied and it is unknown if RS-induced microbial shifts are protective in experimental colitis. Aims Assess efficacy of isomaltodextrin (IMD), a novel RS, to reduce intestinal inflammation in HLA-B27 transgenic (TG) rat colitis model and identify protective mechanisms associated with gut microbial composition and function. Methods 4 week old HLA-B27 TG rats were fed standard chow supplemented with: 7.5% IMD (low dose, LD), 15% IMD (high dose, HD), negative control (15% cellulose, NC), or positive control (15% fructooligosaccharides, PC) for 12 weeks. Body weight and food intake were measured. Cecal and colonic inflammation assessed by weight/length ratio, macroscopic scoring and mucosal IL-1β secretion. Changes in microbial energy metabolism evaluated by measuring short chain fatty acid (SCFA) production in stool and cecal contents. Endpoint fecal and cecal microbiota composition differences assessed by 16S rRNA gene sequencing (Illumina MiSeq platform). Results IMD showed dose-dependent effect on cecal inflammation, measured by macroscopic tissue scoring, weight/length ratio and IL-1β secretion. HD rats had significantly lower cecum IL-1β concentration compared to NC (q=0.01), while LD showed only a trend (q=0.09). HD had significantly higher cecal amounts of Bacteroidaceae and Allobaculum spp. and lower amounts of Peptostreptococcaceae, Eubacterium and Barnesiella spp. versus the LD and NC. HD was associated with significantly higher total SCFA compared to NC (q<0.01) and showed a trend of higher total SCFA than LD (q=0.06). Analysis of SCFAs revealed propionate, isobutyrate and valerate ratios were significantly lower in HD than LD and NC. HD showed a trend of higher ratio of butyrate + acetate compared to NC. This suggests increased carbohydrate fermentation by acetate-producing and -converting microbial groups. Correlation analysis confirmed IL-1β concentrations were positively associated with isobutyrate (r=0.52, q<0.01), valerate (r=0.54, q<0.01), and propionate (r=0.48, q<0.01), suggesting their use as chronic inflammation markers in HLA-B27 models. Conclusions IMD was dose-dependently effective in reducing chronic cecal inflammation in experimental colitis. Benefits were associated with specific shifts in gut microbiome composition and SCFA production. Results from this preclinical study warrant future microbiota-altering intervention trials using IMD in clinical IBD. Funding Agencies Hayashibara Co., Ltd.
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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 | 0.000 |
| 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".