Sex and regional effects of in the gut.

spp. is a key immune-programming microbe in healthy individuals - these bacteria have been shown to be reduced in abundance across a variety of disease states. Our study investigated the systemic and region-specific responses to colonization in the gut, including sex-related differences, in mice. Utilizing C57BL/6 mice, we administered to conventional, antibiotic-treated mice, then assessed this microbe's influence on the gut microbiota composition and inflammatory responses following an airway lipopolysaccharide challenge to assess effects on the gut-lung axis. We found that successfully colonizes the intestinal tract of antibiotic-treated mice, particularly the colon lumen of the large intestine as evidenced by 16S rRNA amplicon gene sequencing and culturing. Differential gene expression analysis using NanoString technology revealed significant immune response variations across the gut regions, with notable differences in adaptive immune response genes. A striking sex-dependent outcome was noted in the regulation of in the cecum, potentially enhancing autophagic function, particularly in female mice. Additionally, intestinal colonization was associated with altered expression of macrophage markers such as , , and , which may reflect shifts in the macrophage profile within the cecum. These findings pave the way for novel therapeutic approaches that leverage microbial impacts on gut and systemic health, offering a deeper understanding of ' role in human health and disease. Our study highlights the necessity for further research to elucidate the intricate relationships between gut microbiota, host immunity, biological sex and their interplay.