Host immune constraints define the window of opportunity for microbial colonization during the early life of Larimichthys crocea

Early-life microbiota succession in teleost fish is crucial for immune development and host-microbe homeostasis, yet mechanisms directing microbial assembly during critical developmental windows remain poorly understood. Here, using<i> Larimichthys crocea </i>as a model, we demonstrated that larval microbiota assembly is dynamically governed by stochastic and deterministic processes, peaking at days post-hatching (DPH)18 with maximal neutral model fit (R²=0.71) and migration rate (m=0.88). Alpha diversity followed a hump-shaped trajectory, dominated by Comamonas, inversely correlating with Vibrio at DPH18. Host-derived microbes outweighed diet and water in shaping communities. Crucially, transcriptional profiling revealed active immune modulation. Pro-inflammatory pathways (e.g., IL-17 signaling) were upregulated before DPH18, while anti-inflammatory regulators (e.g., <i>tgfb2</i> (transforming growth factor, beta 2)) declined during development, indicating transient immune constraints. Zebrafish dexamethasone-induced immune constraints caused intestinal barrier dysfunction and microbial dysbiosis when immune tolerance was disrupted. Collectively, we identified DPH3–DPH18 as a critical colonization window for L. crocea wherein host immune constraints highlight an evolutionary strategy to prioritize niche establishment. This temporal constraint optimizes microbial resilience and long-term disease resistance, offering a mechanistic basis for early-life interventions in teleost development.