Sex differences in the intestinal microbiome: interactions with risk factors for atherosclerosis and cardiovascular disease
Bibliographic record
Abstract
BACKGROUND: There are clearly sex differences in cardiovascular disease. On average, women experience cardiovascular events at an older age, and at any age, women, on average, have less atherosclerotic plaque than men. The role of the human intestinal microbiome in health and disease has garnered significant interest in recent years, and there have been indications of sex differences in the intestinal microbiome. The purpose of this narrative review was to evaluate evidence of sex differences in the interaction between the intestinal microbiome and risk factors for cardiovascular disease. Several studies have demonstrated changes in microbiota composition and metabolic profile as a function of diet, sex hormones, and host metabolism, among other factors. This dysbiosis has consequently been associated with several disease states, including atherosclerosis and cardiovascular disease. In this respect, there is a growing appreciation for the microbiota and its secreted metabolites, including trimethylamine N-oxide (TMAO), derived from intestinal bacterial metabolic pathways involving dietary choline and L-carnitine, as novel risk factors for atherosclerosis and cardiovascular outcomes. Although traditional risk factors for vascular disease have been studied broadly over the years, there exists little research to evaluate interactions of cardiovascular risk factors with a potentially sexually dimorphic intestinal microbiome. This review evaluates the role of sex differences in the composition of the intestinal microbiome, including effects of sex hormones on the microbiome, and the effects of these sex differences on cardiovascular risk factors. Diabetes and obesity exhibit sexual dimorphism, while the data concerning hypertension and dyslipidemia remain inconclusive based on the available literature. In addition, an increased proportion of gram-negative species capable of driving metabolic endotoxemia and a low-grade inflammatory response, as well as decreased numbers of butyrate-producing species, have been observed in relation to traditional vascular risk factors. In this context, circulating SCFAs and TMAO are recognized as key metabolites of the intestinal microbiome that can be readily measured in the blood for the evaluation of metabolic profile. CONCLUSION: Novel strategies focused on resolving intestinal dysbiosis as a means to slow progression of atherosclerosis and reduce the risk of cardiovascular disease should be evaluated through a lens of sex differences.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".