The Impact of <i>Lactobacillus paracasei</i> subsp. <i>Paracasei</i> on Oxytetracycline‐Induced Anxiety‐Like Behavior of Zebrafish via Regulation of Gut Microbiota and Brain Fatty Acid Metabolism

ABSTRACT The use of oxytetracycline (OTC) in aquaculture is crucial for fish health and disease prevention, but it might accumulate in humans through the food chain, potentially affecting neural tissues and ultimately inducing anxiety‐like behaviors. This study assessed the effect of Lactobacillus paracasei subsp. paracasei ( LPSP ) in reversing OTC‐induced anxiety‐like behaviors through the gut–brain axis in zebrafish model. By novel tank diving test and the light/dark preference test, LPSP could inhibit exacerbated thigmotaxis and scototaxis behavior of zebrafish induced by OTC. Brain metabolomics revealed that LPSP supplement ameliorated the OTC‐induced suppression of α‐linolenic acid, linoleic acid, and glycerophospholipid metabolism and further elevated brain neurotransmitter levels. In addition, intestinal 16S rRNA analysis showed that LPSP helped to restore the richness and diversity of intestinal microbiota reduced by OTC. It could mitigate the increase in Proteobacteria abundance induced by OTC. Besides, the LPSP supplement was beneficial for increasing the relative abundance of native Firmicutes in the intestinal microbiota of zebrafish, including Lactobacillus reuteri , Lactobacillus johnsonii , and Lactococcus lactis subsp. cremoris . According to the correlation network analysis, the increased abundance of the species was largely correlated with the restoration of α‐linolenic acid, linoleic acid, and glycerophospholipid metabolism in brain tissue.