Dietary Fat and Fiber Divergently Control Intestinal Nanoplastic Bioaccumulation through Gut Motility and Barrier Pathways

The ingestion of nanoplastics (NPs) poses a growing environmental health threat, yet how intrinsic host factors modulate their intestinal fate remains poorly defined. This study tests the hypothesis that dietary patterns govern NP bioaccumulation by differentially regulating gut motility and barrier integrity. Mice were fed a control (CD), high-fat (HFD), or high-fiber diet (HFib) and exposed to 0, 5, or 25 mg/kg/day of deuterium-labeled polystyrene NPs for 8 weeks. Dietary composition profoundly altered colonic NP accumulation: compared to CD-fed mice, an HFD exacerbated the burden by 2.83-fold (328.6 ± 23.5 μg/g dry weight), whereas a HFib attenuated it to 34% (38.9 ± 7.6 μg/g). This differential accumulation was linked to barrier damage and motility suppression, most severe under HFD. Multiomics analysis revealed that HFD promoted gut dysbiosis and deficiency of short-chain fatty acids, particularly butanoic acid. This metabolic deficit was associated with disrupted enteric nervous system signaling, notably suppressed serotonergic pathways. Integrative path modeling delineated two mechanistic landscapes: a barrier-centric pathogenic cascade driven by HFD and a microbiota-led protective network sustained by HFib. Our findings establish host nutrition as a potent modifier of NP intestinal fate and accumulation, highlighting dietary fiber as a plausible nutritional strategy to enhance intestinal resilience.