Valls Rebecca A, Barrack Kaitlyn E, Surve Sarvesh V, Bliska James B, O'Toole George A
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, USA.
bioRxiv. 2025 Aug 27:2025.08.27.672693. doi: 10.1101/2025.08.27.672693.
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.
某菌种是健康个体中关键的免疫编程微生物——在多种疾病状态下，这些细菌的丰度已被证明会降低。我们的研究调查了小鼠肠道定植后的全身和区域特异性反应，包括性别差异。利用C57BL/6小鼠，我们将其给予常规的、经抗生素处理的小鼠，然后在气道脂多糖攻击后评估这种微生物对肠道微生物群组成和炎症反应的影响，以评估对肠-肺轴的作用。我们发现，通过16S rRNA扩增子基因测序和培养证明，该菌种成功定殖于抗生素处理小鼠的肠道，特别是大肠的结肠腔。使用NanoString技术进行的差异基因表达分析揭示了肠道各区域显著的免疫反应差异，在适应性免疫反应基因方面存在明显差异。在盲肠中该菌种的调节方面发现了显著的性别依赖性结果，可能增强自噬功能，尤其是在雌性小鼠中。此外，该菌种的肠道定植与巨噬细胞标志物如某些蛋白的表达改变有关，这可能反映了盲肠内巨噬细胞谱的变化。这些发现为利用微生物对肠道和全身健康的影响的新型治疗方法铺平了道路，有助于更深入地了解该菌种在人类健康和疾病中的作用。我们的研究强调了进一步研究以阐明肠道微生物群、宿主免疫、生物性别及其相互作用之间复杂关系的必要性。
