Host-derived probiotics are microorganisms sourced from the host's gut environment, aimed at enhancing growth and overall health. Given the increasing stringency in the regulation of antibiotics within animal production, the adoption of in-feed probiotics has emerged as a compelling antibiotic alternative in aquaculture. Here, we investigate the impact of Pseudomonas monteilii JK-1 on the growth performance and disease resistance of grass carp (Ctenopharyngodon idella). The results indicate that P. monteilii JK-1 leads to a significant increase in weight gain (WG), specific growth rate (SGR), and survival rate, along with a substantial reduction in pathogen load (Aeromonas) (P < 0.05). Furthermore, we observed a noteworthy improvement in the expression of key immune-related genes, including interleukin 1β (IL-1β), interleukin 10 (IL10), tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-β) in both the head kidney and gut (P < 0.05). This effect extends to the augmentation of the activities of crucial antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in both liver and gut tissues (P < 0.05). Notably, P. monteilii JK-1 exerts a positive influence on the complexity of the gut microbiome ecological network. In this context, Cetobacterium emerges as a keystone microbiota responsible for maintaining interspecies interactions and enhancing gut network stability. Moreover, our study establishes a positive connection between Cetobacterium and growth performance and between Akkemansia and immune response, respectively. In addition, the result of partial least squares path model (PLS-PM) showed that P. monteilii JK-1 does not directly enhance growth performance and pathogen resistance but does so by regulating keystone taxa and promoting gut network stability. Collectively, this study offers a nuanced comprehension of how probiotics enhance growth and boost disease resistance, focusing on the gut microbial ecological network. These findings showed that P. monteilii JK-1 has potential application as a probiotic in grass carp, which may provide a new strategy of preventing and controlling bacterial diseases in this species.
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