Phytogenic Bioactive Compounds Shape Fish Mucosal Immunity

Abstract

Aquaculture growth will unavoidably involve the implementation of innovative and sustainable production strategies, being functional feeds among the most promising ones. A wide spectrum of phytogenics, particularly those containing terpenes and organosulfur compounds, are increasingly studied in aquafeeds, due to their growth promoting, antimicrobial, immunostimulant, antioxidant, anti-inflammatory and sedative properties. This trend relies on the importance of the mucosal barrier in the fish defense. Establishing the phytogenics' mode of action in mucosal tissues is of importance for further use and safe administration. Although the impact of phytogenics upon fish mucosal immunity has been extensively approached, most of the studies fail in addressing the mechanisms underlying their pharmacological effects. Unstandardized testing as an extended practice also questions the reproducibility and safety of such studies, limiting the use of phytogenics at commercial scale. The information presented herein provides insight on the fish mucosal immune responses to phytogenics, suggesting their mode of action, and ultimately encouraging the practice of reliable and reproducible research for novel feed additives for aquafeeds. For proper screening, characterization and optimization of their mode of action, we encourage the evaluation of purified compounds using in vitro systems before moving forward to in vivo trials. The formulation of additives with combinations of compounds previously characterized is recommended to avoid bacterial resistance. To improve the delivery of phytogenics and overcome limitations associated to compounds volatility and susceptibility to degradation, the use of encapsulation is advisable. Besides, newer approaches and dedicated methodologies are needed to elucidate the phytogenics pharmacokinetics and mode of action in depth.

Keywords: MALT; TRPV4; immunity; organosulfurs; phytogenic additive; sustainable aquaculture; teleost; terpenes.

Figure 1

Suggested mechanisms of cell activation by the transient receptor potential (TRP) cation channels mediated by phytogenics’ bioactive compounds in mucosal-associated lymphoid tissues (MALTs). Bioactive compounds activate TRP channels leading to intracellular Ca²⁺ increase and non-canonical activation of the TAK complex. In parallel, stimulation by pathogen-associated molecular patterns (PAMPs) may facilitate the activation of TLR and TRP signaling pathways. Modified from Galindo-Villegas, et al. (124). TLR, toll-like receptors; MyD88, myeloid differentiation primary response 88; TAK, transforming growth factor beta (TGFβ) activated kinase; TAB, TGFβ activated kinase binding protein; ROS, reactive oxygen species; NF-kB, nuclear factor kappa-B; IKK, inhibitor of NF-kB kinase; MAPK, mitogen-activated protein kinase; AP1, activator protein 1; CYP, cytochromes P450; P, phosphorylation.

Figure 2

Summary of the proposed mode of response induced by phytogenic bioactive compounds in fish mucosal tissues. The effects against representative types of common pathogens on the most studied mucosal-associated lymphoid tissues in fish so far are represented in the figure. (A) Gills. (B) Gut. (C) Skin. Gilthead seabream (S. aurata) was used in the figure as a representative aquaculture-relevant fish.