Microbiome and Metabolic Disease – High Fat Diet (HFD)- Induced Obesity and Antibiotic Pre-treatment

Description

Differential responses to metabolic disease can be observed in animals pre-treated with antibiotic, likely due to perturbation or reduction of the constitutive microbiome. Depending on the antibiotic pre-treatment paradigm selected, evaluation of obesity and metabolism phenotype in antibiotic pre-treated animals enables assessment of phenotypes’ sensitivity toward broad microbiome depletion, species-specific depletion, or function-specific depletion. Data assessing metabolic phenotypes in normal mice, as well as from the high fat diet-induced obesity model, utilizing animals pre-treated with an antibiotic cocktail intended for maximum microbiome depletion is shown. A subset of animals were treated with a murine fecal microbial transplant (FMT).

Model Systems
  • C57Bl/6 Mice
Standard Readouts
  • Percent weight change
  • Body composition via DEXA: bone mineral density & content, bone area, lean & fat mass, body fat percentage
  • Blood glucose
Additional Readouts
  • Oral glucose tolerance test
  • Terminal histopathology and/or IHC analyses
  • Peripheral cytokine analysis
  • Serum chemistry analysis
  • Serum triglyceride and cholesterol analysis
  • Peripheral lymphoid organ immunophenotyping
  • Bacterial load (culture/qPCR)
  • Sequencing and metagenomics
  • Custom assays
Representative DataClick Image to Enlarge
Percent Weight Change in Normal Mice Following Antibiotic Pre-Treatment

Animals are weighed daily, and body weight change as compared to Day 0 is calculated. The AUC is calculated to compare treatment arms and is shown in the inset. (***p<0.005).

Pre- and Post-Prandial Blood Glucose in Normal Mice Following Antibiotic Pre-Treatment

Animals are fasted and blood glucose is measured via glucose monitor. Food is returned to animals and blood glucose is re-measured via glucose monitor the next day.

Bone Phenotypes (DEXA) in Normal Mice Following Antibiotic Pre-Treatment

Bone phenotypes are assessed via dual-energy x-ray absorptiometry (DEXA) analysis. (*p<0.05; **p<0.01; ***p<0.005; ****p<0.001).

Tissue Phenotypes (DEXA) in Normal Mice Following Antibiotic Pre-Treatment

Tissue phenotypes are assessed via dual-energy x-ray absorptiometry (DEXA) analysis. (*p<0.05).

Percent Weight Change in DIO Mice Following Antibiotic Pre-Treatment

Animals are weighed daily, and body weight change as compared to day of HFD administration (Day 22) is calculated. The AUC is calculated to compare treatment arms and is shown in the inset. (*p<0.05; **p<0.01; ***p<0.005; ****p<0.001).

Pre- and Post-Prandial Blood Glucose in DIO Mice Following Antibiotic Pre-Treatment

Animals are fasted and blood glucose is measured via glucose monitor. Food is returned to animals and blood glucose is re-measured via glucose monitor the next day.

Bone Phenotypes (DEXA) in DIO Mice Following Antibiotic Pre-Treatment

Bone phenotypes are assessed via dual-energy x-ray absorptiometry (DEXA) analysis.

Tissue Phenotypes (DEXA) in DIO Mice Following Antibiotic Pre-Treatment

Tissue phenotypes are assessed via dual-energy x-ray absorptiometry (DEXA) analysis. (**p<0.01; ***p<0.005; ****p<0.001).

Daniel Lichtman

Managing Partner