Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides
Year: 2025
Type: article
Abstract: 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.
Source: Nature Communications
Institutions: Pennsylvania State University, Yale University
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Harnessing the gut microbiome to detect and quantify glycans, Elucidating the consequences of dietary sugar consumption on the gut microbiota, G3425524420, G4018405822, G4122164632, G4900767475, G5456536456, G5933690935, Control of gut colonization by the prominent gut bacterium Bacteroides thetaiotaomicron, G8008075946, G815468949, G9000019278, G9000080967, G93911698
OpenAlex ID: W4410360667