New insights into the genetic predisposition of brucellosis and its effect on the gut and vaginal microbiota in goats.

Goats contribute significantly to the global food security and industry. They constitute a main supplier of meat and milk for large proportions of people in Egypt and worldwide. Brucellosis is a zoonotic infectious disease that causes a significant economic loss in animal production. A case-control genome-wide association analysis (GWAS) was conducted using the infectious status of the animal as a phenotype. The does that showed abortion during the last third period of pregnancy and which were positive to both rose bengal plate and serum tube agglutination tests, were considered as cases. Otherwise, they were considered as controls. All animals were genotyped using the Illumina 65KSNP BeadChip. Additionally, the diversity and composition of vaginal and fecal microbiota in cases and controls were investigated using PCR-amplicone sequencing of the V4 region of 16S rDNA. After applying quality control criteria, 35,818 markers and 66 does were available for the GWAS test. The GWAS revealed a significantly associated SNP (P = 5.01 × 10-7) located on Caprine chromosome 15 at 29 megabases. Four other markers surpassed the proposed threshold (P = 2.5 × 10-5). Additionally, fourteen genomic regions accounted for more than 0.1% of the variance explained by all genome windows. Corresponding markers were located within or in close vicinity to several candidate genes, such as ARRB1, RELT, ATG16L2, IGSF21, UBR4, ULK1, DCN, MAPB1, NAIP, CD26, IFIH1, NDFIP2, DOK4, MAF, IL2RB, USP18, ARID5A, ZAP70, CNTN5, PIK3AP1, DNTT, BLNK, and NHLRC3. These genes play important roles in the regulation of immune responses to the infections through several biological pathways. Similar vaginal bacterial community was observed in both cases and controls while the fecal bacterial composition and diversity differed between the groups (P < 0.05). Faeces from the control does showed a higher relative abundance of the phylum Bacteroidota compared to cases (P < 0.05), while the latter showed more Firmicutes, Spirochaetota, Planctomycetota, and Proteobacteria. On the genus level, the control does exhibited higher abundances of Rikenellaceae RC9 gut group and Christensenellaceae R-7 group (P < 0.05), while the infected does revealed higher Bacteroides, Alistipes, and Prevotellaceae UCG-003 (P < 0.05). This information increases our understanding of the genetics of the susceptibility to Brucella in goats and may be useful in breeding programs and selection schemes that aim at controlling the disease in livestock.