Abstract
The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male University of California, Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats before the onset of diabetes (prediabetic PD; n = 15), 2 wk recently diabetic (RD; n = 10), 3 mo (D3M; n = 11), and 6 mo (D6M; n = 8) postonset of diabetes. Bacterial species and functional gene counts were assessed by shotgun metagenomic sequencing of bacterial DNA in cecal contents, while metabolites were identified by gas chromatography-quadrupole time-off-flight-mass spectrometry. Metagenomic analysis showed a shift from Firmicutes species in early stages of diabetes (PD = RD) toward an enrichment of Bacteroidetes species in later stages of diabetes (D3M = D6M). In total, 45 bacterial species discriminated early and late stages of diabetes with 25 of these belonging to either Bacteroides or Prevotella genera. Furthermore, 61 bacterial gene clusters discriminated early and later stages of diabetes with elevations of enzymes related to stress response (e.g., glutathione and glutaredoxin) and amino acid, carbohydrate, and bacterial cell wall metabolism. Twenty-five cecal metabolites discriminated early vs. late stages of diabetes, with the largest differences observed in abundances of dehydroabietic acid and phosphate. Alterations in the gut microbiota and cecal metabolome track diabetes progression in UCD-T2DM rats when controlling for diet, age, and housing environment. Results suggest that diabetes-specific host signals impact the ecology and end product metabolites of the gut microbiome when diet is held constant.
| Original language | English (US) |
|---|---|
| Pages (from-to) | E961-E972 |
| Journal | American Journal of Physiology - Endocrinology and Metabolism |
| Volume | 315 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1 2018 |
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Keywords
- Diabetes
- Metabolomics
- Metagenomics
- Microbiota
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Physiology (medical)
Cite this
Diabetes-associated alterations in the cecal microbiome and metabolome are independent of diet or environment in the uc davis type 2 diabetes mellitus rat model. / Piccolo, Brian D.; Graham, James L.; Stanhope, Kimber; Nookaew, Intawat; Mercer, Kelly E.; Chintapalli, Sree V.; Wankhade, Umesh D.; Shankar, Kartik; Havel, Peter J; Adams, Sean H.
In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 315, No. 5, 01.11.2018, p. E961-E972.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Diabetes-associated alterations in the cecal microbiome and metabolome are independent of diet or environment in the uc davis type 2 diabetes mellitus rat model
AU - Piccolo, Brian D.
AU - Graham, James L.
AU - Stanhope, Kimber
AU - Nookaew, Intawat
AU - Mercer, Kelly E.
AU - Chintapalli, Sree V.
AU - Wankhade, Umesh D.
AU - Shankar, Kartik
AU - Havel, Peter J
AU - Adams, Sean H.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male University of California, Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats before the onset of diabetes (prediabetic PD; n = 15), 2 wk recently diabetic (RD; n = 10), 3 mo (D3M; n = 11), and 6 mo (D6M; n = 8) postonset of diabetes. Bacterial species and functional gene counts were assessed by shotgun metagenomic sequencing of bacterial DNA in cecal contents, while metabolites were identified by gas chromatography-quadrupole time-off-flight-mass spectrometry. Metagenomic analysis showed a shift from Firmicutes species in early stages of diabetes (PD = RD) toward an enrichment of Bacteroidetes species in later stages of diabetes (D3M = D6M). In total, 45 bacterial species discriminated early and late stages of diabetes with 25 of these belonging to either Bacteroides or Prevotella genera. Furthermore, 61 bacterial gene clusters discriminated early and later stages of diabetes with elevations of enzymes related to stress response (e.g., glutathione and glutaredoxin) and amino acid, carbohydrate, and bacterial cell wall metabolism. Twenty-five cecal metabolites discriminated early vs. late stages of diabetes, with the largest differences observed in abundances of dehydroabietic acid and phosphate. Alterations in the gut microbiota and cecal metabolome track diabetes progression in UCD-T2DM rats when controlling for diet, age, and housing environment. Results suggest that diabetes-specific host signals impact the ecology and end product metabolites of the gut microbiome when diet is held constant.
AB - The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male University of California, Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats before the onset of diabetes (prediabetic PD; n = 15), 2 wk recently diabetic (RD; n = 10), 3 mo (D3M; n = 11), and 6 mo (D6M; n = 8) postonset of diabetes. Bacterial species and functional gene counts were assessed by shotgun metagenomic sequencing of bacterial DNA in cecal contents, while metabolites were identified by gas chromatography-quadrupole time-off-flight-mass spectrometry. Metagenomic analysis showed a shift from Firmicutes species in early stages of diabetes (PD = RD) toward an enrichment of Bacteroidetes species in later stages of diabetes (D3M = D6M). In total, 45 bacterial species discriminated early and late stages of diabetes with 25 of these belonging to either Bacteroides or Prevotella genera. Furthermore, 61 bacterial gene clusters discriminated early and later stages of diabetes with elevations of enzymes related to stress response (e.g., glutathione and glutaredoxin) and amino acid, carbohydrate, and bacterial cell wall metabolism. Twenty-five cecal metabolites discriminated early vs. late stages of diabetes, with the largest differences observed in abundances of dehydroabietic acid and phosphate. Alterations in the gut microbiota and cecal metabolome track diabetes progression in UCD-T2DM rats when controlling for diet, age, and housing environment. Results suggest that diabetes-specific host signals impact the ecology and end product metabolites of the gut microbiome when diet is held constant.
KW - Diabetes
KW - Metabolomics
KW - Metagenomics
KW - Microbiota
UR - http://www.scopus.com/inward/record.url?scp=85056567624&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056567624&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00203.2018
DO - 10.1152/ajpendo.00203.2018
M3 - Article
C2 - 30016149
AN - SCOPUS:85056567624
VL - 315
SP - E961-E972
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0193-1849
IS - 5
ER -