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Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes
A prodigious number of microbes inhabit the human body, especially in the lumen of the gastrointestinal (GI) tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metabolism, we analyzed ATP levels an...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460890/ https://www.ncbi.nlm.nih.gov/pubmed/23029553 http://dx.doi.org/10.1371/journal.pone.0046589 |
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author | Donohoe, Dallas R. Wali, Aminah Brylawski, Bruna P. Bultman, Scott J. |
author_facet | Donohoe, Dallas R. Wali, Aminah Brylawski, Bruna P. Bultman, Scott J. |
author_sort | Donohoe, Dallas R. |
collection | PubMed |
description | A prodigious number of microbes inhabit the human body, especially in the lumen of the gastrointestinal (GI) tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metabolism, we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germfree and conventionally-raised C57BL/6 mice. These experiments demonstrated that microbiota are required for energy homeostasis in the proximal colon to a greater extent than other segments of the GI tract that also harbor high densities of bacteria. This tissue-specific effect is consistent with colonocytes utilizing bacterially-produced butyrate as their primary energy source, whereas most other cell types utilize glucose. However, it was surprising that glucose did not compensate for butyrate deficiency. We measured a 3.5-fold increase in glucose uptake in germfree colonocytes. However, (13)C-glucose metabolic-flux experiments and biochemical assays demonstrated that they shifted their glucose metabolism away from mitochondrial oxidation/CO(2) production and toward increased glycolysis/lactate production, which does not yield enough ATPs to compensate. The mechanism responsible for this metabolic shift is diminished pyruvate dehydrogenase (PDH) levels and activity. Consistent with perturbed PDH function, the addition of butyrate, but not glucose, to germfree colonocytes ex vivo stimulated oxidative metabolism. As a result of this energetic defect, germfree colonocytes exhibited a partial block in the G(1)-to-S-phase transition that was rescued by a butyrate-fortified diet. These data reveal a mechanism by which microbiota regulate glucose utilization to influence energy homeostasis and cell-cycle progression of mammalian host cells. |
format | Online Article Text |
id | pubmed-3460890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34608902012-10-01 Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes Donohoe, Dallas R. Wali, Aminah Brylawski, Bruna P. Bultman, Scott J. PLoS One Research Article A prodigious number of microbes inhabit the human body, especially in the lumen of the gastrointestinal (GI) tract, yet our knowledge of how they regulate metabolic pathways within our cells is rather limited. To investigate the role of microbiota in host energy metabolism, we analyzed ATP levels and AMPK phosphorylation in tissues isolated from germfree and conventionally-raised C57BL/6 mice. These experiments demonstrated that microbiota are required for energy homeostasis in the proximal colon to a greater extent than other segments of the GI tract that also harbor high densities of bacteria. This tissue-specific effect is consistent with colonocytes utilizing bacterially-produced butyrate as their primary energy source, whereas most other cell types utilize glucose. However, it was surprising that glucose did not compensate for butyrate deficiency. We measured a 3.5-fold increase in glucose uptake in germfree colonocytes. However, (13)C-glucose metabolic-flux experiments and biochemical assays demonstrated that they shifted their glucose metabolism away from mitochondrial oxidation/CO(2) production and toward increased glycolysis/lactate production, which does not yield enough ATPs to compensate. The mechanism responsible for this metabolic shift is diminished pyruvate dehydrogenase (PDH) levels and activity. Consistent with perturbed PDH function, the addition of butyrate, but not glucose, to germfree colonocytes ex vivo stimulated oxidative metabolism. As a result of this energetic defect, germfree colonocytes exhibited a partial block in the G(1)-to-S-phase transition that was rescued by a butyrate-fortified diet. These data reveal a mechanism by which microbiota regulate glucose utilization to influence energy homeostasis and cell-cycle progression of mammalian host cells. Public Library of Science 2012-09-28 /pmc/articles/PMC3460890/ /pubmed/23029553 http://dx.doi.org/10.1371/journal.pone.0046589 Text en © 2012 Donohoe et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Donohoe, Dallas R. Wali, Aminah Brylawski, Bruna P. Bultman, Scott J. Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes |
title | Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes |
title_full | Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes |
title_fullStr | Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes |
title_full_unstemmed | Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes |
title_short | Microbial Regulation of Glucose Metabolism and Cell-Cycle Progression in Mammalian Colonocytes |
title_sort | microbial regulation of glucose metabolism and cell-cycle progression in mammalian colonocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460890/ https://www.ncbi.nlm.nih.gov/pubmed/23029553 http://dx.doi.org/10.1371/journal.pone.0046589 |
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