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Abstract

Biogenesis of lysosome-related organelles complex 1 subunit 1 ( BLOC1S1, also known as BLOS1 ) is a key gene involved in phagosome-lysosome maturation, transport, and autophagosome fusion, and it plays a crucial role in host resistance to Brucella infection. This study aimed to examine the effects of BLOS1 overexpression (oeBLOS1) on the stress response of goat macrophages and on intestinal microbiota composition. Peripheral blood mononuclear cells (PBMCs) were isolated from oeBLOS1 and wild-type (WT) goats and differentiated into macrophages. These macrophages were then stimulated with Brucella LPS to assess cytokine secretion and autophagy levels. Metagenomic sequencing was also performed to analyze the structural and functional profiles of the rectal fecal microbiota in these goats. After Brucella LPS stimulation, oeBLOS1 goat macrophages rapidly activated the NF-κB and TLR4 signaling pathways, promoting the synthesis and secretion of cytokines such as TNF-α ( P < 0.05). Brucella LPS challenge also significantly increased the transcription of autophagy-related genes such as LAMP2 and BECN1 , enhancing autophagic activity and bacterial clearance ( P < 0.05) . Furthermore, oeBLOS1 altered the intestinal microbiota, significantly enriching pathways linked to membrane transport and cell motility, and reducing the abundance of virulence factors and opportunistic pathogens, which may contribute to intestinal immune homeostasis. In summary, oeBLOS1 may help counteract Brucella LPS-induced infection by promoting the immune response, enhancing autophagy. In addition, it is associated with remodeling gut microbial function, suggesting a potential role in disease resistance.