Mandal, R. N.; Ke, J.; Kanika, N. H.; Hou, X.; Zhang, Z.; Zhang, P.; Chen, H.; Zeng, C.; Chen, X.; Wang, J.; Wang, C.

The gut microbiome is one of the major regulators of the gut-skin axis and partly regulated by host genetics. In the present study, using comparative high-throughput omics data on CRISPR/Cas9-mediated TYRP1 mutant and wild color common carp populations, we quantified the proportion of inter-individual variation in the skin transcriptome and blood metabolome by genetic architecture and gut microbiomes. We found 525 differential metabolites (DMs) and 45 differential gut microbial genera in TYRP1 mutant fishes relative to wild type. Through interaction analysis and causal mediation analyses, we revealed that the TYRP1-mutant derived genetic background may exert an inflammatory Acinetobacter - Leukotrience-C4 and Spermine metabolic pathway under the regulation of an anti-inflammatory cardio-vascular genetic network underlying the upregulating expression of COMT, PLG, C2, C3, F10, TDO2, MHC1, and SERPINF2 gene for evolving unusual coffee-like color phenotype. This unique network appears to underlie the \"coffee-like\" color phenotype. We propose that the COMT-mediated causal effect of unusual gut microbiome on the atypical skin gene expression patterns through gut-skin metabolic pathway.