An opportunistic pathogen isolated fromthe gut of an obese human causesobesity in germfree mice                           ...
Case• weight 174.8 kg,• body mass index 58.8 kgm2• suffering from diabetes, hypertension and other serious  metabolic dete...
How does it happen?• Biomedical Indicator
Key Point----Enterobactera genus of opportunistic, endotoxin producingPathogens, made up 35% of the gut bacteria in amorbi...
HypothesisThe endotoxin producing Enterobacterpopulation may have a causative role in themetabolic deteriorations of its h...
Animal StudiesAnimal:Germfree (GF) male C57BL/6J mice*  *germfree mice are resistant to HFD-induced obesityClinical isolat...
(continued)4 groups:•   NCD+B29•   NCD+LB•   HFD+B29•   HFD+LBdata collected at the end of 16 weeks after inoculation• Bod...
Body weight after 16 weeks of experiment
Fat pad after 16 weeks of experiment
Blood Glucose level after 16 weeks of experiment
Conclusion from the data collected• The HFD+B29 gnotobiotic mice developed the  most significant insulin resistant phenoty...
Serum LPS-binding protein after 16 weeks*B29 was the only LPS producer in the gnotobiotic-mouse gut
Conclusion from the LBP level after 16 weeks experiment • The serum LPS-binding protein was significantly higher in the   ...
Serum SAA and adiponection level after the 16 weeksHFD+B29 mice had the greatest increase in systemicinflammation
Conclusion of the studyOvergrowth of an endotoxin producing gutbacterium is a contributing factor to, rather thana consequ...
Strength of the study• for the first time, established a gnotobiotic-mouse obesity  model combining HFD with a human-origi...
Several question remains uncertain• Study is conducted for 16 weeks, it’s uncertain if the  gut pathogen from the obese fu...
Thank You!We Appreciate Your Patience
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An opportunistic pathogen isolated from the gut of

  1. 1. An opportunistic pathogen isolated fromthe gut of an obese human causesobesity in germfree mice Lisa Luna Medical Primary Care
  2. 2. Case• weight 174.8 kg,• body mass index 58.8 kgm2• suffering from diabetes, hypertension and other serious metabolic deteriorations• on a diet composed of whole grains, traditional Chinese medicinal foods and prebiotics• lost 30.1 kg after 9 weeks, and 51.4 kg after 23 weeks• Amelioration of hyperinsulinemia, hyperglycemia and hypertension until most metabolic parameters improved to normal ranges
  3. 3. How does it happen?• Biomedical Indicator
  4. 4. Key Point----Enterobactera genus of opportunistic, endotoxin producingPathogens, made up 35% of the gut bacteria in amorbidly obese volunteerAfter 9 weeks on the WTP diet*, this Enterobacterpopulation in the volunteer’s gut reduced to 1.8%, andbecame undetectable by the end of the 23-week trial*WTP Diet :whole grains, traditional Chinese medicine and prebiotics
  5. 5. HypothesisThe endotoxin producing Enterobacterpopulation may have a causative role in themetabolic deteriorations of its human host
  6. 6. Animal StudiesAnimal:Germfree (GF) male C57BL/6J mice* *germfree mice are resistant to HFD-induced obesityClinical isolation:• Strain Enterobacter cloacae B29 isolated from the volunteer’s gut• and nearest neighbor as E.cloacae subsp. cloacae ATCC 13047Process:Inoculation of B29 and Luria–Bertani (LB) into GF miceFeed:• normal chow diet (NCD) or• High fat diet(HFD)
  7. 7. (continued)4 groups:• NCD+B29• NCD+LB• HFD+B29• HFD+LBdata collected at the end of 16 weeks after inoculation• Body weight• mass of epididymal, mesenteric, subcutaneous inguinal and retroperitoneal fat pad;• oral glucose tolerance test (OGTT) and areas under the curve (AUC) for the plasma glucose;• serum 2h post load insulin;• enzyme-linked immunosorbent assay (ELISA) analysis of serum LPS-binding protein (LBP);• serum amyloid A (SAA);• adiponectin corrected for bodyweight
  8. 8. Body weight after 16 weeks of experiment
  9. 9. Fat pad after 16 weeks of experiment
  10. 10. Blood Glucose level after 16 weeks of experiment
  11. 11. Conclusion from the data collected• The HFD+B29 gnotobiotic mice developed the most significant insulin resistant phenotype and body gain and other characteristics of obesity• The NCD+B29or NCD+LB both remained lean throughout the trial
  12. 12. Serum LPS-binding protein after 16 weeks*B29 was the only LPS producer in the gnotobiotic-mouse gut
  13. 13. Conclusion from the LBP level after 16 weeks experiment • The serum LPS-binding protein was significantly higher in the HFD+B29 gnotobiotic mice than in the NCD+B29 • increased serum–endotoxin load in the HFD+B29 gnotobiotic mice could only come from B29.
  14. 14. Serum SAA and adiponection level after the 16 weeksHFD+B29 mice had the greatest increase in systemicinflammation
  15. 15. Conclusion of the studyOvergrowth of an endotoxin producing gutbacterium is a contributing factor to, rather thana consequence of, the metabolic deteriorationsin its human host
  16. 16. Strength of the study• for the first time, established a gnotobiotic-mouse obesity model combining HFD with a human-originated endotoxin producer• identify more such obesity-inducing bacteria from various human populations• develop new strategies for reducing the devastating epidemic of metabolic diseases
  17. 17. Several question remains uncertain• Study is conducted for 16 weeks, it’s uncertain if the gut pathogen from the obese functions the similar way in a long term.• B29 is probably not the only contributor to human obesity in vivo.• More case study is required to replicate the experiments
  18. 18. Thank You!We Appreciate Your Patience

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