Characterization of interactions of dietary cholesterol with the murine and human gut microbiome
Bibliographic record
Abstract
Consumption of dietary lipids, such as cholesterol, modulates the gut microbiome with consequences for host health through the production of microbiome-derived metabolites. Despite the implications for host metabolism, a limited number of specific interactions of the gut microbiome with diet-derived lipids have been characterized. This is partially because obtaining species-level resolution of the responsible taxa can be challenging and additional approaches are needed to identify health-relevant metabolites produced from cholesterol-microbiome interactions. Here we performed bio-orthogonal labelling sort sequence spectrometry, a click chemistry based workflow, to profile cholesterol-specific host-microbe interactions. Mice were exposed to an alkyne-functionalized variant of cholesterol and 16S ribosomal RNA gene amplicon sequencing of faecal samples identified diet-derived cholesterol-interacting microbes from the genera Bacteroides, Bifidobacterium, Enterococcus and Parabacteroides. Shotgun metagenomic analysis provided species-level resolution of diet-derived cholesterol-interacting microbes with enrichment of bile acid-like and sulfotransferase-like activities. Using untargeted metabolomics, we identify that cholesterol is converted to cholesterol sulfate in a Bacteroides-specific manner via the enzyme BT_0416. Mice monocolonized with Bacteroides thetaiotaomicron lacking Bt_0416 showed altered host cholesterol and cholesterol sulfate compared with wild-type mice, identifying a previously uncharacterized microbiome-transformation of cholesterol and a mechanism for microbiome-dependent contributions to host phenotype. Moreover, identification of a cholesterol-responsive sulfotransferase in Bacteroides suggests diet-dependent mechanisms for altering microbiome-specific cholesterol metabolism. Overall, our work identifies numerous cholesterol-interacting microbes with implications for more precise microbiome-conscious regulation of host cholesterol homeostasis.
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 | 0.000 | 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) | 0.001 | 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".