Gallic acid acts as an anti-inflammatory agent via PPARγ-mediated immunomodulation and antioxidation in fish gut-liver axis

Abstract

Gallic acid's therapeutic potential for addressing fish enteritis is attributed to its capacity to interact with zebrafish PPARγ. Notably, the administration of gallic acid supplementation within a soybean meal diet has been shown to manifest anti-inflammatory effects, thereby contributing to the preservation of intestinal and hepatic well-being. Histology results showed that both the villi length and CD4 signals in the intestinal mucosa were comparable to the healthy control group. The inflammatory aggregation of neutrophils, macrophages, and T lymphocytes in larvae's hindgut was also suppressed. In 3-month-old zebrafish, the typical hepatic markers associated with soybean meal-induced inflammation, such as lipid droplets and accumulating macrophages, were reduced. Examination of transcriptome data through enrichment analysis revealed a discernible modulation of pathways. Specifically, there was a notable downregulation observed in pathways associated with intestinal cytokines, apoptosis, and oxidative phosphorylation. Concurrently, pathways related to the upregulation of immunosuppressive short-chain fatty acids and arginine were evident. The prominent hepatic processes that were suppressed were connected to fatty acid metabolism. After the intestinal microbiota's 16S rRNA gene sequencing, the ratio of Firmicutes and Bacteroides was found to be comparable to that in the healthy control. The presence of more Verrucomicrobia may protect the intestinal barrier and the proportion of commensal Shewanella increased, matched by fewer pathogens in the gallic acid group. The gut metabolome then indicated an increase in anti-inflammatory and anti-oxidative compounds and pathways, such as those related to tryptophan, arginine, linoleic acid, and histidine metabolism. Through an integrative assessment associating differentially expressed genes with altered gut metabolites, a compilation of potential anti-enteritis metabolites emerged. These metabolites exhibited pertinent associations with immunoregulatory genes, such as il21, il22, tnfrsf118, and mapkapk3. This intricate interplay underscores the plausible involvement of metabolic crosstalk between the host and the microbial milieu in driving anti-inflammatory mechanisms. Notably, gallic acid, through the stimulation of PPARγ-mediated immunomodulatory pathways and antioxidative processes within the fish gut-liver axis, is posited to mitigate instances of foodborne inflammation.