Altered Tryptophan Metabolism and Gut Immune Crosstalk in Hypertensive Middle-Aged Women (Data Supplement)
Bibliographic record
Abstract
Data Supplement for Altered Tryptophan Metabolism and Gut Immune Crosstalk in Hypertensive Middle-Aged Women. ABSTRACT: The gut microbiome is increasingly recognized as a contributing factor in the pathogenesis of hypertension; however, there remains a significant gap regarding its role in middle-aged women, a demographic that has unique physiological and hormonal characteristics influencing both microbiome composition and blood pressure. Normotensive and hypertensive middle-aged women (n=108) from Alberta’s Tomorrow Project (AB, Canada) were matched for age (56.6 ± 0.9 years) and body mass index (24.3 ± 0.2 kg/m²). Fecal microbiota was analyzed using 16S rRNA sequencing while serum was assessed using untargeted metabolomics and lipidomics. Hypertensive women exhibited selective taxonomic shifts, evidenced by an elevated Firmicutes/Bacteroidetes ratio and enrichment of pro-inflammatory taxa, including <i>Anaerostipes</i> and <i>Collinsella</i>. Circulating levels of tryptophan and its pro-inflammatory metabolite kynurenine were significantly elevated, while microbiota-derived indoles, known for their anti-inflammatory effects were reduced. This metabolic shift was paralleled by a depletion of indole-producing species (<i>Alistipes shahii</i>, <i>Bacteroides faecichinchillae</i>, <i>Bacteroides stercoris</i>), suggesting impaired microbial tryptophan-to-indole conversion. Serum inflammatory cytokines, including interferon-γ, tumor necrosis factor-α, and an elevated IL-12/IL-10 ratio, were increased in hypertensive participants. Notably, kynurenine was positively correlated with the IL-12/IL-10 ratio. Hypertension in middle-aged women is associated with altered abundance of functionally relevant taxa characterized by shifts in tryptophan metabolism toward pro-inflammatory kynurenine pathways at the expense of protective indole derivatives. Collectively, these findings highlight gut-immune-metabolic cross-talk contributing to hypertension and suggest microbiota-regulated tryptophan metabolism as a potentially modifiable therapeutic target.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.335 | 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".