1. An opportunistic pathogen isolated from
the gut of an obese human causes
obesity in germfree mice
Lisa
Luna Medical Primary Care

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. How does it happen?
• Biomedical Indicator

4. Key Point----Enterobacter
a genus of opportunistic, endotoxin producing
Pathogens, made up 35% of the gut bacteria in a
morbidly obese volunteer
After 9 weeks on the WTP diet*, this Enterobacter
population in the volunteer’s gut reduced to 1.8%, and
became undetectable by the end of the 23-week trial
*WTP Diet :whole grains, traditional Chinese medicine and prebiotics

5. Hypothesis
The endotoxin producing Enterobacter
population may have a causative role in the
metabolic deteriorations of its human host

6. Animal Studies
Animal:
Germfree (GF) male C57BL/6J mice*
*germfree mice are resistant to HFD-induced obesity
Clinical isolation:
• Strain Enterobacter cloacae B29 isolated from the volunteer’s gut
• and nearest neighbor as E.cloacae subsp. cloacae ATCC 13047
Process:
Inoculation of B29 and Luria–Bertani (LB) into GF mice
Feed:
• normal chow diet (NCD) or
• High fat diet(HFD)

7. (continued)
4 groups:
• NCD+B29
• NCD+LB
• HFD+B29
• HFD+LB
data 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. Body weight after 16 weeks of experiment

9. Fat pad after 16 weeks of experiment

10. Blood Glucose level after 16 weeks of experiment

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. Serum LPS-binding protein after 16 weeks
*B29 was the only LPS producer in the gnotobiotic-mouse gut

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. Serum SAA and adiponection level after the 16 weeks
HFD+B29 mice had the greatest increase in systemic
inflammation

15. Conclusion of the study
Overgrowth of an endotoxin producing gut
bacterium is a contributing factor to, rather than
a consequence of, the metabolic deteriorations
in its human host

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. 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. Thank You!
We Appreciate Your Patience