Bacterial indole-3-butyric acid promotes fish PUFA synthesis

Marine fish are paradoxically rich in polyunsaturated fatty acids (PUFAs) despite limited endogenous biosynthetic capacity, suggesting a critical contribution from the gut microbiota. Here, we first characterized the gut microbiota of Seriola dumerili, a PUFA-rich marine fish, functionally enriched in the biosynthesis of unsaturated fatty acids. Further functional validation was performed using zebrafish as a model. Strain screening revealed the Bacillus thuringiensis strain Sd_h10 exhibited potent lipid utilization capacity in vitro and in zebrafish on a high-fat diet, and remodeled transcription of lipid-related pathways to promote lipid accumulation and PUFA biosynthesis. Notably, indole-3-butyric acid (IBA), a major metabolite of Sd_h10, was found in the intestinal tissue of S. dumerili and regulated peroxisome proliferator-activated receptor gamma (PPARγ), mimicking the effects of the PPARγ agonist rosiglitazone in zebrafish. Long-term IBA administration in conventional zebrafish increased body weight gain, hepatic lipid accumulation, and muscle docosahexaenoate (DHA) content, accompanied by upregulation of PPARγ downstream target genes, including dgat2, fads6, and elovl6l. Simultaneously, IBA reshaped the intestinal microbiota, depleting Burkholderiaceae while enriching Acidovorax abundance, accompanied by enrichment of functions related to fatty acid uptake, lipid utilization, and unsaturated fatty acid modification. These findings support a potential role for the microbiota-derived metabolite IBA in modulating PPARγ-associated signaling pathways linked to host DHA biosynthesis and accumulation. Our study provides additional evidence supporting microbiota-host lipid metabolic interactions and highlights the potential application of probiotic-associated microbial metabolites for improving lipid nutritional quality in marine fish.