Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides
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 pr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59704-3 |
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| author | Seth G. Kabonick Kamalesh Verma Jennifer L. Modesto Victoria H. Pearce Kailyn M. Winokur Eduardo A. Groisman Guy E. Townsend |
| author_facet | Seth G. Kabonick Kamalesh Verma Jennifer L. Modesto Victoria H. Pearce Kailyn M. Winokur Eduardo A. Groisman Guy E. Townsend |
| author_sort | Seth G. Kabonick |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d8e02df1fd2a4dcf903b7ece1e4acf10 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d8e02df1fd2a4dcf903b7ece1e4acf102025-08-20T02:25:16ZengNature PortfolioNature Communications2041-17232025-05-0116111010.1038/s41467-025-59704-3Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut BacteroidesSeth G. Kabonick0Kamalesh Verma1Jennifer L. Modesto2Victoria H. Pearce3Kailyn M. Winokur4Eduardo A. Groisman5Guy E. Townsend6Penn State College of MedicinePenn State College of MedicinePenn State College of MedicinePenn State College of MedicinePenn State College of MedicineYale University School of MedicinePenn State College of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-59704-3 |
| spellingShingle | Seth G. Kabonick Kamalesh Verma Jennifer L. Modesto Victoria H. Pearce Kailyn M. Winokur Eduardo A. Groisman Guy E. Townsend Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides Nature Communications |
| title | Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides |
| title_full | Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides |
| title_fullStr | Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides |
| title_full_unstemmed | Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides |
| title_short | Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut Bacteroides |
| title_sort | hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut bacteroides |
| url | https://doi.org/10.1038/s41467-025-59704-3 |
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