A9 BACTERIAL BILE SALT HYDROLASE GENE ABUNDANCE IS ASSOCIATED WITH RORC GENE EXPRESSION IN INTESTINAL MUCOSA OF INFLAMMATORY DISEASE PATIENTS
Bibliographic record
Abstract
Abstract Background The role of gut microbes involved in bile acid metabolism and their impact on mucosal immune regulation is beginning to be appreciated. For instance, changes in microbial bile salt hydrolase (BSH) activity which deconjugates bile acids in the gastrointestinal tract of gnotobiotic mice, significantly alters gene expression patterns of immune-related genes in ileum. Moreover, bile acid dysmetabolism may participate in the chronic inflammation loop of Inflammatory bowel disease (IBD). Aims We carried out an integrated mucosal microbiome-transcriptome analysis to elucidate associations between microbial bile-acid metabolizing function and host gene expression. Methods Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) patients were recruited prior to scheduled colonoscopy performed as part of clinical care. Only patients with non-inflamed mucosa defined as a segmental simple endoscopic score 0–2 in CD and a segmental Mayo endoscopic score of 0 in UC/IBDU were included in this analysis to minimize the effect of inflammation on gene expression. Biopsy samples were obtained from terminal ileum, ascending colon and sigmoid colon, and microbial DNA and human RNA was extracted. V4 region of 16S rRNA gene was sequenced and the relative abundance of bile acid-metabolizing genes was inferred using PICRUSt. RNA-seq was used to sequence total human RNA and a supervised transcript reduction analysis focus upon 65 genes previously associated with bile acid metabolism and IBD was utilized. Associations between microbiome clusters of orthologous groups (COGs), transcriptome, diagnosis (CD vs UC/IBDU), and biopsy site were analyzed using linear mixed-effects model with lmer4 function in R. An adjusted-p value after false discovery rate correction < 0.05 was considered significant. Results A total of 126 samples from 86 subjects were analyzed corresponding to 35 CD and 51 UC/IBDU. Mean age for the total cohort was 34.7 ± 11 years and 35 (40.6%) were females. There was a significant negative correlation between relative abundance of bacterial bsh genes (COG3049) and human RORC gene (p < 0.03). This association was independent of type of diagnosis and biopsy site. There was no association among other analyzed bacterial COGs and host genes. Conclusions Using an integrative microbiome-host transcriptome approach, our data provide new evidence linking microbial bile acid deconjugation (bsh genes) and host gene expression in the mucosal-luminal interface in quiescent IBD-affected tissue. Nuclear receptor RORC is pivotal in the differentiation and function of innate lymphoid cells and T-helper 17 cells. Modulation of this pathway by bile acids or gut bacteria involved in their metabolism could shed light on the immune role of bile acids in IBD patients. Funding Agencies CAG, CIHRNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.003 | 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".