A98 PLASMA BIOMARKER MAY DETECT DISEASE-DEPENDENT ALTERATIONS IN GUT MICROBIOTA IN IBD: A PILOT STUDY
Bibliographic record
Abstract
Ulcerative colitis (UC) is chronic, often relapsing, remitting inflammation affecting the rectum to proximal colon. UC activity is linked to reduced gut microbial diversity. Trimethylamine-N-oxide (TMAO) is a quantifiable plasma metabolite produced from dietary choline and carnitine through a microbial-mammalian pathway. A previous study by our group demonstrated decreased plasma TMAO was associated with UC. It was hypothesized that changes in the gut microbial profile accounted for differences in plasma TMAO concentrations. To evaluate the gut microbial profile of subjects with UC and healthy controls to determine if it is predictive of plasma TMAO concentrations. Thirty-three subjects (13 control (C), 20 UC) were recruited and informed consent was obtained. Demographic and disease activity data were collected. Liquid chromatography-tandem mass spectrometry was used to measure TMAO and dietary choline plasma concentrations. A combined 132 sigmoid colon pinch biopsies were taken during colonoscopy to quantify the mucosal-adherent microbial profile. The abundance of five bacterial genera (Bacteroides prevotella (Bp), Clostridium XIV (CXIV), Bifidobacterium longum (Bl), Lactobacillus (L), Enterobacteriaceae (E)), representative of the 4 main bacterial phyla present in the gastrointestinal tract, were quantified from biopsies using real-time PCR. TMAO plasma concentrations were reduced in UC compared to healthy controls (UC: 1.027 ± 0.896, C: 5.478 ± 3.655, p <0.001) and when adjusted for dietary choline plasma concentrations (UC: 0.149 ± 0.232, C:0.643 ± 0.388, p<0.0001). Relative to the total microbiome, Enterobacteriaceae, Lactobacillus and Clostridium XIV were decreased in the UC population compared to the control population (E: UC: 0.714 ± 1.67, C: 1.16 ± 2.49, p=0.28; L: UC: 0.035 ± 0.043, C: 0.042 ± 0.057, p=0.72; CXIV, UC: 1.16 ± 1.51, C: 2.82 ± 5.09, p=0.28). Conversely, in the UC population, Bacteroides prevotella and Bifidobacterium longum were increased relative to the total microbiome (Bp: UC: 6.37 ± 7.22, C: 3.59 ± 2.53, p=0.15; Bl: UC: 0.32±-0.51, C: 0.11 ± 0.15, p=0.11). Studies of the microbiome did not reach statistical significance. This pilot study shows that TMAO plasma concentrations are significantly reduced in patients with UC, even when normalized for choline plasma concentrations. Microbial profiles appear to be different in individuals with UC compared to a healthy population. TMAO-producing Enterobacteriaceae, Lactobacillus and Clostridium XIV were under-represented compared to the total microbiome in individuals with UC. This suggests that differences in the gut microbial profile in UC versus healthy individuals may be detectable by a plasma-based biomarker. Expansion of the sample size is needed to confirm these findings. CAG, 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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".