Overexpression of <i>ASMT</i> likely enhances the resistance of transgenic sheep to brucellosis by influencing immune?related signaling pathways and gut microbiota

Melatonin is a pleiotropic molecule with variety of biological functions, which include its immunoregulatory action in mammals. Brucellosis worldwide endemic zoonotic disease caused by the Brucella, not only causes huge economic losses for livestock industry but also impacts human health. To target this problem, current study, two marker-free transgenic sheep overexpressing melatonin synthetic enzyme ASMT (acetylserotonin O-methyltransferase) gene were generated and these enrich challenged Brucella infection. The results showed that serum concentration was significantly higher than wild type (726.92 ± 70.6074 vs 263.10 34.60 pg/mL, P < .05). challenge test thirds (4/6) wild-type had brucellosis, while none infected. Whole-blood RNA-seq differential expression genes (DEGs) enriched natural killer cell-mediated cytotoxicity, phagosome, antigen processing, presentation signaling pathways overexpression sheep. DEGs toll-like receptors (TLRs) NOD-like (NLRs) families verified qPCR it TLR1, TLR2, TLR7, CD14, NAIP, CXCL8 levels NLRP1, NLRP3, TNF lower those type. rectal feces subjected to 16S rDNA amplicon sequencing, microbial functional analysis abundance related infectious diseases compared type, indicating animals are likely more resistant Furthermore, exogenous treatment relieved brucellosis inflammation upregulating anti-inflammatory cytokines IL-4 downregulating pro-inflammatory IL-2, IL-6, IFN-?. Our preliminary provide an informative reference study relationship between brucellosis.