Intestinal Bacillus sp. derived IBA activates PPARγ to promote PUFA synthesis in fish

Background: Marine fish are paradoxically rich in polyunsaturated fatty acids (PUFAs) despite their limited endogenous biosynthesis capacity, suggesting a critical role of exogenous acquisition or microbial contributions.
Results: Here, we characterized the gut microbiota of Seriola dumerili, a PUFA-rich marine fish, functionally enriched in biosynthesis of unsaturated fatty acids. Strain screening revealed the Bacillus thuringiensis strain Sd_h10 exhibited potent lipid utilization capacity in vitro and in fish under 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 also abundant in S. dumerili gut tissue, directly bound to and activated peroxisome proliferator-activated receptor gamma (PPARγ), mimicking the effects of the PPARγ agonist rosiglitazone. Long-term IBA administration in conventional zebrafish increased body weight gain, hepatic lipid accumulation, and muscle docosahexaenoate (DHA) content accompanied with 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.
Conclusions: These findings established IBA as an efficient microbial-derived PPARγ agonist contributing to host PUFA biosynthesis and accumulation, providing in depth understanding of host-microbe interactions and highlighting the conserved microbiota–PPARγ–lipid regulatory axis with potential relevance to human lipid metabolic disorders.