Urease in acetogenic <i>Lachnospiraceae</i> drives urea carbon salvage in SCFA pools
Bibliographic record
Abstract
The gut microbiota produces short-chain fatty acids (SCFA) and acidifies the proximal colon which inhibits enteric pathogens. However, for many microbiota constituents, how they themselves resist these stresses is unknown. The anaerobic Lachnospiraceae family, which includes the acetogenic genus Blautia, produce SCFA, are genomically diverse, and vary in their capacity to acidify culture media. Here, we investigated how Lachnospiraceae tolerate pH stress and found that subunits of urease were associated with acidification in a random forest model. Urease cleaves urea into ammonia and carbon dioxide, however the role of urease in the physiology of Lachnospiraceae is unknown. We demonstrate that urease-encoding Blautia show urea-dependent changes in SCFA production, acidification, growth, and, strikingly, urease encoding Blautia directly incorporate the carbon from urea into SCFAs. In contrast, ureolytic Klebsiella pneumoniae or Proteus mirabilis do not show the same urea-dependency or carbon salvage. In agreement, the combination of urease and acetogenesis functions is rare in gut taxa. We find that Lachnospiraceae urease and acetogenesis genes can be co-expressed in healthy individuals and colonization of mice with a ureolytic Blautia reduces urea availability in colon contents demonstrating Blautia urease activity in vivo. In human and mouse microbial communities, the acetogenic recycling of urea carbon into acetate by Blautia leads to the incorporation of urea carbon into butyrate indicating carbon salvage into broader metabolite pools. Altogether, this shows that urea plays a central role in the physiology of health-associated Lachnospiraceae which use urea in a distinct manner that is different from that of ureolytic pathogens.
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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 | 0.001 |
| 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) | 0.000 | 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".