Fecal deoxycholic acid associates with diet, intestinal microbes, and total bilirubin in primary sclerosing cholangitis
Bibliographic record
Abstract
Background & Aims Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease and variable disease progression. We aimed to gain insights into the role of fecal bile acids (BA) on disease progression by determining the relationships between fecal BA, diet, and gut microbes, with markers of disease progression, BA synthesis, and farnesoid X receptor (FXR) activity. Methods BA levels in serum and stool, dietary intake, and markers of BA synthesis, and FXR activity were measured in 26 patients with early stage, large duct PSC. Fecal microbiota were quantified by 16S rRNA gene sequencing. Results Compared with controls, fecal unconjugated deoxycholic acid (DCA) levels were lower in patients with PSC ( p adj = 0.04). Alcohol intake and the abundance of Blautia and Lachnoclostridium were associated with greater fecal DCA levels in patients with PSC after adjusting for inflammatory bowel disease and treatment with ursodeoxycholic acid. Fecal DCA levels were negatively associated with total bilirubin levels in patients with PSC ( p = 0.006) suggesting a protective role. However, fecal DCA was associated with greater serum levels of 7α-hydroxy-4-cholesten-3-one, a marker of BA synthesis, and was not associated with fibroblast growth factor 19, a marker of intestinal FXR activity. Conclusions Alcohol intake, Blautia and Lachnoclostridium abundance was associated with increased fecal DCA levels, which in turn seemed to have had a protective effect in patients with early-stage PSC. However, this effect was not mediated by BA synthesis or FXR activation. Impact and implications Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with a direct interaction between the gut and the liver. In this study of patients with early-stage PSC, levels of fecal deoxycholic acid correlated with serum total bilirubin, a marker of clinical outcomes. In addition, Blautia and Lachnoclostridium were associated with fecal deoxycholic acid suggesting an interaction between these gut bacteria, fecal bile acids, and disease progression. Future research to determine the underlying mechanisms of these associations may lead to novel targets to prevent PSC disease progression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".