Circadian Disruption Elicits Sex-Specific Gut Microbiota, Endocannabinoidome and Lipid Mediator Responses
Bibliographic record
Abstract
Abstract Circadian disruption is a pervasive environmental stressor that increases susceptibility to metabolic and inflammatory diseases, yet sex-specific adaptive strategies remain poorly understood. Here, we show that constant light (LL) exposure alters gut microbial communities and triggers sex- and tissue-specific host adaptations in the endocannabinoidome and other bioactive lipids. Using 16S rRNA sequencing, short chain fatty acid (SCFA) quantification, LC-MS/MS lipidomics, and cytokine profiling, we identified divergent coping strategies across brain, metabolic and intestinal tissues and reproductive organs. In females, LL induced microbial restructuring, with enrichment of Rikenellaceae , Butyricicoccaceae , and Alistipes , but these changes were uncoupled from short-chain fatty acids (SCFA) output. Also, they engaged N -acylethanolamine (NAE)-driven endocannabinoidome signaling in the brain (AEA, DHEA, OEA, PEA, SEA), accompanied by omega-6 prostaglandin upregulation and increased cytokines (IL-5, IFN-γ, MIP-2). The 2-monoacyl glycerols (2-MAGs) increased selectively in liver and skeletal muscle, reflecting tissue-specific lipid remodeling. In males, microbial shifts were limited (e.g., Ruminococcaceae depletion, Tuzzerella enrichment), yet LL triggered robust metabolic adaptation resulting in elevated SCFA levels (isobutyric, butyric, isovaleric, valeric acids) in faeces and elevation of several DHA-derived bioactive lipids in different intestinal tissues Few alterations in brain bioactive lipids were found, while several 2-MAGs were elevated skeletal muscles and testes. In contrast, several oxylipins were decreased within subcutaneous but not other adipose tissue depots. Together, the data shows that changes in bioactive lipid levels in response to circadian rhythm disruption are organ- and sex-specific as are alterations in microbiota populations, positioning sex as a key determinant of responses to circadian stress.
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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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".