Integrated transcriptomic and microbiota analyses reveal growth-related intestinal responses to feeding strategies in...

Feeding strategies critically influence intestinal homeostasis in farmed fish, however, their underlying regulatory mechanisms remain poorly understood. Nibea coibor, a fish species with local characteristics in Zhanjiang (Guangdong Province, China), was chosen as the experimental model for studying feeding strategies. This study employed integrated multi-omics analyses to systematically dissect the multidimensional regulatory networks of four different feeding strategies on intestinal morphology, transcriptome, and microbiota in Nibea coibor. Feeding strategies reshaped gut microbiota composition and significantly altered gene expression. Compared with daytime feeding (DF), continuous fasting (CF) induced villus atrophy and goblet cell loss, disrupted microbial homeostasis (Vibrio, Actinomyces, Photobacterium, and Akkermansia upregulation), and triggered transcriptional reprogramming (pfkfb4, pla2g12b, rptor, and pecam1 downregulation; col1a upregulation). In contrast, intermittent fasting (IF, two-day fasting/one-day feeding) achieved optimal intestinal health with the highest goblet cell density, villus height, and microbial diversity, suggesting microbiota-mediated gut plasticity and adaptation. Nighttime feeding (NF) elicited minor downregulation of energy metabolism genes without causing significant morphological or microbial alterations, indicating limited short-term circadian effects. Finally, the PLS-PM model delineated the cascade regulatory relationships linking gut microbiota, transcriptome, and intestinal morphology. These findings highlight intermittent fasting as a promising strategy to sustain intestinal homeostasis through microbiota-host synergy, while underscoring the risks of prolonged fasting-induced metabolic and barrier dysfunction. This work provides valuable insights for refining feeding protocols in marine fish aquaculture, especially N. coibor.