Kabonick Seth G, Verma Kamalesh, Modesto Jennifer L, Pearce Victoria H, Winokur Kailyn M, Groisman Eduardo A, Townsend Guy E
Penn State College of Medicine, Hershey, PA, USA.
Penn State One Health Microbiome Center, Pennsylvania State University, State College, PA, USA.
Nat Commun. 2025 May 14;16(1):4488. doi: 10.1038/s41467-025-59704-3.
Human dietary choices control the gut microbiome. Industrialized populations consume abundant amounts of glucose and fructose, resulting in microbe-dependent intestinal disorders. Simple sugars inhibit the carbohydrate utilization regulator (Cur), a transcription factor in members of the prominent gut bacterial phylum, Bacteroidetes. Cur controls products necessary for carbohydrate utilization, host immunomodulation, and intestinal colonization. Here, we demonstrate how simple sugars decrease Cur activity in the mammalian gut. Our findings in two Bacteroides species show that ATP-dependent fructose-1,6-bisphosphate (FBP) synthesis is necessary for glucose or fructose to inhibit Cur, but dispensable for growth because of an essential pyrophosphate (PPi)-dependent enzyme. Furthermore, we show that ATP-dependent FBP synthesis is required to regulate Cur in the gut but does not contribute to fitness when cur is absent, indicating PPi is sufficient to drive glycolysis in these bacteria. Our findings reveal how sugar-rich diets inhibit Cur, thereby disrupting Bacteroides fitness and diminishing products that are beneficial to the host.
人类的饮食选择控制着肠道微生物群。工业化人群摄入大量的葡萄糖和果糖，导致依赖微生物的肠道疾病。单糖会抑制碳水化合物利用调节因子（Cur），这是肠道主要细菌门类拟杆菌属成员中的一种转录因子。Cur控制碳水化合物利用、宿主免疫调节和肠道定植所必需的产物。在此，我们展示了单糖如何降低哺乳动物肠道中Cur的活性。我们在两种拟杆菌属物种中的研究结果表明，依赖ATP的果糖-1,6-二磷酸（FBP）合成对于葡萄糖或果糖抑制Cur是必需的，但由于一种必需的焦磷酸（PPi）依赖性酶，它对生长是可有可无的。此外，我们表明依赖ATP的FBP合成是在肠道中调节Cur所必需的，但当Cur缺失时对适应性没有贡献，这表明PPi足以驱动这些细菌中的糖酵解。我们的研究结果揭示了高糖饮食如何抑制Cur，从而破坏拟杆菌属的适应性并减少对宿主有益的产物。
