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TRUVACE RECORD VERSION
record: TRV-2026-0998
version: 2
kind: revised
reason: Direction audit: the gain line stated no AI consequence and was removed; the problem line stated no AI consequence and was removed. Filed as context; not counted as a gain or a problem.
timestamp: 2026-10-26T06:38:48.318013Z
status: published
lens: general
sector: health
headline: The tire antioxidant derivative 6PPD-quinone exacerbates IBD by targeting NR1H4-mediated lipid metabolism and mitochondrial dysfunction in human colon epithelial cells
dek: N- (1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), a tire rubber antioxidant derivative, accumulates in air, soil, and water and has been found in urine, blood, and cerebrospinal fluid, posing significant health risks. Although 6PPD-Q exhibits intestinal toxicity, its role in inflammatory bowel disease (IBD) remains unclear. The objective of this study was to identify key molecular targets of 6PPD-Q in IBD and to validate their involvement in 6PPD-Q-induced intestinal epithelial cell injury. U…
gain_title: Multi-model machine learning screening of 6PPD-Q-IBD targets identified 60 overlapping targets and prioritized six core genes with NR1H4 as a key mediator of intestinal epithelial injury.
problem_title: Machine learning-informed toxicology analysis indicates 6PPD-quinone exposure increases IBD risk in human colon epithelial cells by downregulating NR1H4, causing lipid and cholesterol accumulation, mitochondrial dysfunction, and elevated IL-6, TNF-alpha, and IL-8.
trace_subject: (none)
gain_reading: Multi-model machine learning screening of 6PPD-Q-IBD targets identified 60 overlapping targets and prioritized six core genes with NR1H4 as a key mediator of intestinal epithelial injury.
gain_evidence: Multi-model machine learning screened six core genes (NR1H4, ANXA5, SPARC, PCK1, PDK2, and CFB), with NR1H4 as a key mediator. | Using network toxicology, machine learning, molecular docking, and in vitro experiments in human intestinal epithelial cells, we identified 60 overlapping 6PPD-Q-IBD targets, enriched in lipid metabolism, oxidative stress, and inflammation.
problem_reading: Machine learning-informed toxicology analysis indicates 6PPD-quinone exposure increases IBD risk in human colon epithelial cells by downregulating NR1H4, causing lipid and cholesterol accumulation, mitochondrial dysfunction, and elevated IL-6, TNF-alpha, and IL-8.
problem_evidence: These findings reveal that 6PPD-Q increases IBD risk by interfering with lipid metabolism, disrupting mitochondrial function, upregulating inflammatory cytokines, and downregulating NR1H4
quick_read: Researchers used network toxicology, multi-model machine learning, molecular docking, and in vitro experiments in human intestinal epithelial cells to probe the tire-derived pollutant 6PPD-quinone. The workflow identified 60 overlapping 6PPD-Q-IBD targets and prioritized six core genes, with NR1H4 as a key mediator that binds strongly to 6PPD-Q.

The work matters because it connects an emerging environmental pollutant found in human biofluids to a plausible IBD mechanism involving lipid droplet and cholesterol accumulation, mitochondrial dysfunction, and inflammatory cytokine upregulation. Uncertainty remains because evidence is computational and cell-based as of the September 2026 publication date, without animal or patient-level IBD outcomes.
limitation: Findings are limited to computational screening and in vitro human intestinal epithelial cell experiments without in vivo or clinical IBD patient validation.
tag: Context
key_points: Network toxicology and machine learning identified 60 overlapping 6PPD-Q-IBD targets enriched in lipid metabolism, oxidative stress, and inflammation. | Multi-model machine learning narrowed to six core genes NR1H4, ANXA5, SPARC, PCK1, PDK2, and CFB, with NR1H4 highlighted as key mediator. | Molecular docking showed strong binding of 6PPD-Q to NR1H4, exceeding that of its parent compound. | In vitro validation in human intestinal epithelial cells showed lipid droplet and cholesterol accumulation, mitochondrial dysfunction, and upregulation of IL-6, TNF-alpha, and IL-8 with downregulation of NR1H4.
rundown: The study combined network toxicology, machine learning, molecular docking, and cell experiments to investigate the tire antioxidant derivative 6PPD-quinone, which accumulates in air, soil, water and has been found in urine, blood, and cerebrospinal fluid.

Computational screening found 60 overlapping 6PPD-Q-IBD targets and six core genes, with docking showing strong binding of 6PPD-Q to NR1H4 exceeding its parent compound, followed by in vitro confirmation of ATP synthesis inhibition, mitochondrial ROS burst, decreased membrane potential, and mitochondrial fragmentation.
sources:
- peer_reviewed | Food and Chemical Toxicology | https://doi.org/10.1016/j.fct.2026.116379 | 2026-09-04
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