Metabolites

Background: Cultivation environments impose distinct abiotic and biotic stresses that act as primary drivers reshaping the metabolic profile and microbiome assembly of medicinal plants. This study investigates the impact of simulative habitat versus arched greenhouse cultivation on the synthesis of bioactive ginsenosides and the associated root microbiome structure in Panax ginseng. Methods: A combined metabolomics and microbiomics approach was applied to compare ginsenoside accumulation and rhizosphere microbial community composition under the two cultivation modes. Results: Ginseng from simulative habitat cultivation exhibited significantly higher ginsenoside content, particularly ginsenoside Re, compared to arched greenhouse cultivation, with this advantage being more pronounced in long-term cultivation. Microbiome profiling revealed that specific taxa, including Bradyrhizobium, were strongly enriched in simulative habitats and positively correlated with enhanced ginsenoside accumulation, suggesting a microbiome-mediated mechanism for metabolic plasticity. In contrast, arched greenhouse cultivation was associated with a more complex microbial structure characterized by increased negative interactions, which may compromise metabolic quality. Conclusions: These findings, utilizing multi-omics correlations, provide a theoretical basis for optimizing Panax ginseng quality through ecological cultivation strategies that leverage stress-responsive microbe–metabolite interactions.

Background: Pulmonary neuroendocrine cells (PNECs) are rare airway sensory cells implicated in amplifying allergic inflammation, yet due to their scarcity, the contribution of PNECs to the metabolic programs and responses of the airway epithelium remains poorly defined. Using a newly developed PNEC-enriched human airway epithelial model (ePNEC), we investigated the influence of PNECs on neuroendocrine and immune-modulatory metabolite production in response to the common aeroallergen of the house dust mite (HDM). Methods: Human bronchial epithelial cells (HBECs) and ePNEC cultures were differentiated at the air–liquid interface. Global untargeted metabolomics was performed to quantify metabolite abundance at baseline and following stimulation with HDMs. Differential expression, overlap significance, metabolite class enrichment, and pathway analyses were used to define PNEC-specific metabolic programs. Results: Principal component analysis (PCA) demonstrated strong baseline separation between ePNECs and HBECs, with HDMs inducing additional within-cell-type shifts. ePNECs displayed broader and more pronounced metabolite changes than HBECs. Baseline differences were largely preserved following allergen exposure, with significant overlap in both up- and down-regulated metabolites. ePNECs exhibited enriched neurotransmitter-linked metabolites—including serotonin, L-noradrenaline, dopamine, and histamine—at baseline and after HDM exposure. Amino acid–centered metabolism dominated the dataset, with enhanced histidine and tryptophan pathway activity in ePNECs. Pathway analysis revealed significant enrichment of phenylalanine, tyrosine, tryptophan, glutathione, and arginine–proline metabolism in ePNECs, whereas HBECs showed no significant pathway-level enrichment after HDM exposure. Conclusions: Human ePNECs engage a distinct, neuroactive metabolic program that is amplified upon HDM exposure. These findings provide a metabolic framework for how PNECs shape epithelial and neuroimmune responses to inhaled allergens.

Background/Objectives: Circulating inflammatory cytokines and tissue sensitivity are both elevated following heat stress-induced intrauterine growth restriction (IUGR). Cytokines disrupt myoblast function and muscle growth, and thus we hypothesized that suppressing inflammatory tone in IUGR-born lambs by supplementing anti-inflammatory nutraceuticals would improve early postnatal growth. Methods: IUGR lambs produced by maternal heat stress were supplemented daily with 42 mg/kg oral omega-3 polyunsaturated fatty acid (ω-3 PUFA) Ca²⁺ salts or placebo from birth to 28 days of age. Results: By day 28, the 21% lighter bodyweights for IUGR lambs were fully resolved by ω-3 PUFA due to the complete recovery of average daily gain. Subcutaneous fat deposition and visceral organ growth were modestly diminished in IUGR-born lambs, but skeletal muscle mass was more markedly restricted. This coincided with 63% less muscle AdipoR2 but 27% greater circulating adiponectin. ω-3 PUFA reduced or eliminated deficits in subcutaneous fat, visceral organs, and five of the six individual muscles assessed, which corresponded with rescue of myoblast populations and AdipoR2 content. In turn, asymmetric growth restriction was resolved at one month of age. Conclusions: These findings show that targeting heightened inflammatory tone during the neonatal period in IUGR-born offspring can recover early growth in skeletal muscle and other soft tissues.