Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models.
The gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In t...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145499&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850189389044383744 |
|---|---|
| author | Deepak K Rajpal Jean-Louis Klein David Mayhew Joyce Boucheron Aaron T Spivak Vinod Kumar Karen Ingraham Mark Paulik Lihong Chen Stephanie Van Horn Elizabeth Thomas Ganesh Sathe George P Livi David J Holmes James R Brown |
| author_facet | Deepak K Rajpal Jean-Louis Klein David Mayhew Joyce Boucheron Aaron T Spivak Vinod Kumar Karen Ingraham Mark Paulik Lihong Chen Stephanie Van Horn Elizabeth Thomas Ganesh Sathe George P Livi David J Holmes James R Brown |
| author_sort | Deepak K Rajpal |
| collection | DOAJ |
| description | The gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In this study, we used antibiotics with markedly different antibacterial spectra to modulate the gut microbiome in a diet-induced obesity mouse model and then measured relevant biochemical, hormonal and phenotypic biomarkers of obesity and T2DM. Mice fed a high-fat diet were treated with either ceftazidime (a primarily anti-Gram negative bacteria antibiotic) or vancomycin (mainly anti-Gram positive bacteria activity) in an escalating three-dose regimen. We also dosed animals with a well-known prebiotic weight-loss supplement, 10% oligofructose saccharide (10% OFS). Vancomycin treated mice showed little weight change and no improvement in glycemic control while ceftazidime and 10% OFS treatments induced significant weight loss. However, only ceftazidime showed significant, dose dependent improvement in key metabolic variables including glucose, insulin, protein tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Subsequently, we confirmed the positive hyperglycemic control effects of ceftazidime in the Zucker diabetic fatty (ZDF) rat model. Metagenomic DNA sequencing of bacterial 16S rRNA gene regions V1-V3 showed that the microbiomes of ceftazidime dosed mice and rats were enriched for the phylum Firmicutes while 10% OFS treated mice had a greater abundance of Bacteroidetes. We show that specific changes in microbial community composition are associated with obesity and glycemic control phenotypes. More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases. |
| format | Article |
| id | doaj-art-91ca66012e4040b69d7532a6cd1d3711 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-91ca66012e4040b69d7532a6cd1d37112025-08-20T02:15:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014549910.1371/journal.pone.0145499Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models.Deepak K RajpalJean-Louis KleinDavid MayhewJoyce BoucheronAaron T SpivakVinod KumarKaren IngrahamMark PaulikLihong ChenStephanie Van HornElizabeth ThomasGanesh SatheGeorge P LiviDavid J HolmesJames R BrownThe gastrointestinal tract microbiome has been suggested as a potential therapeutic target for metabolic diseases such as obesity and Type 2 diabetes mellitus (T2DM). However, the relationship between changes in microbial communities and metabolic disease-phenotypes are still poorly understood. In this study, we used antibiotics with markedly different antibacterial spectra to modulate the gut microbiome in a diet-induced obesity mouse model and then measured relevant biochemical, hormonal and phenotypic biomarkers of obesity and T2DM. Mice fed a high-fat diet were treated with either ceftazidime (a primarily anti-Gram negative bacteria antibiotic) or vancomycin (mainly anti-Gram positive bacteria activity) in an escalating three-dose regimen. We also dosed animals with a well-known prebiotic weight-loss supplement, 10% oligofructose saccharide (10% OFS). Vancomycin treated mice showed little weight change and no improvement in glycemic control while ceftazidime and 10% OFS treatments induced significant weight loss. However, only ceftazidime showed significant, dose dependent improvement in key metabolic variables including glucose, insulin, protein tyrosine tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Subsequently, we confirmed the positive hyperglycemic control effects of ceftazidime in the Zucker diabetic fatty (ZDF) rat model. Metagenomic DNA sequencing of bacterial 16S rRNA gene regions V1-V3 showed that the microbiomes of ceftazidime dosed mice and rats were enriched for the phylum Firmicutes while 10% OFS treated mice had a greater abundance of Bacteroidetes. We show that specific changes in microbial community composition are associated with obesity and glycemic control phenotypes. More broadly, our study suggests that in vivo modulation of the microbiome warrants further investigation as a potential therapeutic strategy for metabolic diseases.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145499&type=printable |
| spellingShingle | Deepak K Rajpal Jean-Louis Klein David Mayhew Joyce Boucheron Aaron T Spivak Vinod Kumar Karen Ingraham Mark Paulik Lihong Chen Stephanie Van Horn Elizabeth Thomas Ganesh Sathe George P Livi David J Holmes James R Brown Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models. PLoS ONE |
| title | Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models. |
| title_full | Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models. |
| title_fullStr | Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models. |
| title_full_unstemmed | Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models. |
| title_short | Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Obesity and Diabetes Rodent Models. |
| title_sort | selective spectrum antibiotic modulation of the gut microbiome in obesity and diabetes rodent models |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0145499&type=printable |
| work_keys_str_mv | AT deepakkrajpal selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT jeanlouisklein selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT davidmayhew selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT joyceboucheron selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT aarontspivak selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT vinodkumar selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT kareningraham selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT markpaulik selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT lihongchen selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT stephanievanhorn selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT elizabeththomas selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT ganeshsathe selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT georgeplivi selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT davidjholmes selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels AT jamesrbrown selectivespectrumantibioticmodulationofthegutmicrobiomeinobesityanddiabetesrodentmodels |