DIETARY PHYTOBIOTIC ADDITIVE UNLOCKS KEY MOLECULAR PATHWAYS DRIVING ACCELERATED WOUND REPAIR IN ZEBRAFISH

Introduction

Skin integrity is essential for fish health and is the primary biological barrier against environmental stress and pathogens. While the phytobiotic-based feed additive (APEX, Adisseo) has previously been shown to accelerate wound healing and skin regeneration in zebrafish, the underlying mechanisms are not yet fully understood. This study uses transcriptomic analysis to examine how the additive modulates the molecular pathways required for skin repair and barrier restoration.

Material and Methods

Adult zebrafish (Danio rerio) were randomly assigned to three groups: uninjured control, wounded control, and wounded with the additive supplementation. The additive was administered orally twice a week for 14 days before wound induction. Precise 2-mm circular skin wounds were created using laser ablation. At Day 10 post-injury, skin tissues were collected to study gene activity during the active repair phase. Transcriptomic profiling was performed using Illumina paired-end RNA-Seq to identify differentially expressed genes (DEGs) based on the criteria of (|Fold Change| > 2, p.adjust < 0.005) and to characterize specific biological pathways influenced by the additive during the recovery process.

Results

Supplementation with the phytobiotic-based additive significantly improved wound closure efficiency, which represents an increase of nearly 40% compared to the untreated wounded control group. Transcriptomic analysis showed that untreated fish responded to injury with a broad decrease in homeostatic functions. Specifically, blood coagulation and the angiogenic cluster, including regulators such as vegfc, etv2, and robo4, were suppressed, indicating a disruption of the vascular infrastructure needed for nutrient delivery. In contrast, additive supplementation led to a clear reactivation of these molecular processes. The additive increased the activity of pathways related to the steroid biosynthetic process for cholesterol synthesis and cell membrane repair, blood coagulation, complement activation, and the regulation of wound healing. Furthermore, the activation of the PPAR signaling pathway and the presence of the structural protein HSPG2 show that the tissue moved successfully from the inflammatory phase into organized remodeling.

Conclusion

These findings show that the functional additive accelerates skin healing by restoring blood supply and providing essential metabolites for repair. By activating steroid biosynthesis and signaling pathways for growth, the additive effectively supports recovery, leading to faster wound closure and a return to a healthy state.

Figure 1. Zebrafish transcriptomic profiling after skin wounding. Precise laser-induced wounds were used to characterize the molecular mechanisms and signaling pathways modulated by the functional additive during skin repair.

Figure 1. Zebrafish transcriptomic profiling after skin wounding. Precise laser-induced wounds were used to characterize the molecular mechanisms and signaling pathways modulated by the functional additive during skin repair.