Oral Administration of a New Copper (I) Complex with Coumarin as Ligand: Modulation of the Immune Response and the Composition of the Intestinal Microbiota in Onchorhynchus Mykiss

[Cu(NN<inf>1</inf>)<inf>2</inf>]ClO<inf>4</inf> is a copper (I) complex, where NN<inf>1</inf> is an imine ligand 6-((quinolin-2-ylmethylene) amino)-2H-chromen-2-one obtained by derivatization of natural compound coumarin, developed for the treatment of infectious diseases that affect salmonids. In previous research, we showed that the Cu(I) coordination complex possesses antibacterial activity against Flavobacterium psychrophilum, providing protection against this pathogen in rainbow trout during challenge assays (with an RPS of 50%). In the present study, the effects of administering [Cu(NN<inf>1</inf>)<inf>2</inf>]ClO<inf>4</inf> to Oncorhynchus mykiss over a 60-days period were evaluated with regard to systemic immune response and its potential to alter intestinal microbiota composition. In O. mykiss, an immunostimulatory effect was evident at days 30 and 45 after administration, resulting in an increment of transcript levels of IFN-γ, IL-12, TNF-α, lysozyme and perforin. To determine whether these immunomodulatory effects correlated with changes in the intestinal microbiota, we analyzed the metagenome diversity by V4 16S rRNA sequencing. In O. mykiss, both [Cu(NN<inf>1</inf>)<inf>2</inf>]ClO<inf>4</inf> and commercial antibiotic florfenicol had comparable effects at the phylum level, resulting in a predominance of proteobacteria and firmicutes. Nonetheless, at the genus level, florfenicol and [Cu(NN<inf>1</inf>)<inf>2</inf>]ClO<inf>4</inf> complex exhibited distinct effects on the intestinal microbiota of O. mykiss. In conclusion, our findings demonstrate that [Cu(NN<inf>1</inf>)<inf>2</inf>]ClO<inf>4</inf> is capable of stimulating the immune system at a systemic level, while inducing alterations in the composition of the intestinal microbiota in O. mykiss. © © 2024 Parra, Aldabaldetrecu, Arce, Soto-Aguilera, Vargas, Guerrero, Tello and Modak.