Host immune constraints delineate the window of microbial colonization during early development of Larimichthys...

Microbiota assembly during early ontogeny in teleost fish plays a central role in shaping immune maturation and establishing host-microbe homeostasis, yet the regulatory mechanisms driving microbial succession across key developmental windows remain poorly understood. In this study, Larimichthys crocea was used to delineate microbiota assembly dynamics and the impact of stochastic and deterministic processes. Results indicated that community assembly peaked at day 18 post-hatching (DPH18), coinciding with the highest neutral model fit (R ²=0.71) and migration rate (m=0.88). Alpha (α)-diversity exhibited a hump-shaped pattern, with Comamonas dominance inversely correlating with Vibrio at DPH18. Microbial source tracking indicated that host-associated taxa played a more prominent role than dietary or environmental sources. Transcriptomic profiling revealed pronounced immune modulation during early development. Pro-inflammatory signaling, including IL-17 pathway activation, was elevated prior to DPH18, while anti-inflammatory regulators, such as transforming growth factor beta 2 ( tgfb2), declined over time, consistent with a transient reduction in immune restraint. Immune constraints in dexamethasone-treated zebrafish produced intestinal barrier impairment and microbial dysbiosis, demonstrating functional consequences of compromised early immune regulation. Collectively, these patterns defined DPH3-DPH18 as a critical colonization window in L. crocea, during which reduced immune constraint facilitates niche establishment by early colonizers. This temporally restricted window optimizes microbial resilience and long-term resistance to dysbiosis, providing a mechanistic basis for early-life microbiota-directed strategies in teleost development.