Reversible genomic DNA inversions control the expression of numerous gut bacterial molecules, but how this impacts disease remains uncertain. By analyzing metagenomic samples from inflammatory bowel disease (IBD) cohorts, we identified multiple invertible regions where a particular orientation correlated with disease. These include the promoter of polysaccharide A (PSA) of , which induces regulatory T cells (Tregs) and ameliorates experimental colitis. The PSA promoter was mostly oriented “OFF” in IBD patients, which correlated with increased -associated bacteriophages. Similarly, in mice colonized with a healthy human microbiota and , induction of colitis caused a decline of PSA in the “ON” orientation that reversed as inflammation resolved. Monocolonization of mice with revealed that bacteriophage infection increased the frequency of PSA in the “OFF” orientation, causing reduced PSA expression and decreased Treg cells. Altogether, we reveal dynamic bacterial phase variations driven by bacteriophages and host inflammation, signifying bacterial functional plasticity during disease.

中文翻译：

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炎症和噬菌体影响 DNA 反转状态和肠道微生物群的功能

可逆的基因组 DNA 倒置控制着众多肠道细菌分子的表达，但这如何影响疾病仍不确定。通过分析炎症性肠病 (IBD) 队列的宏基因组样本，我们确定了多个可逆区域，其中特定方向与疾病相关。其中包括 的多糖 A (PSA) 启动子，它可诱导调节性 T 细胞 (Treg) 并改善实验性结肠炎。IBD 患者中 PSA 启动子大多呈“OFF”方向，这与相关噬菌体的增加相关。类似地，在健康人类微生物群定植的小鼠中，结肠炎的诱导导致“ON”方向的 PSA 下降，随着炎症消退，PSA 下降。对小鼠的单定植表明，噬菌体感染增加了 PSA 处于“OFF”方向的频率，导致 PSA 表达减少和 Treg 细胞减少。总而言之，我们揭示了由噬菌体和宿主炎症驱动的动态细菌相变化，这表明疾病期间细菌功能的可塑性。