BioTechniques
Bacteria May Cause Diabetes
10/02/2015 Kristie Nybo, PhD
The human microbiome has taken center stage for its roles in diseases as widely varied as malnutrition and asthma. But is it also responsible for diabetes?
Most of the time, Staphylococcus aureus lives harmlessly as a member of the human skin microbiome. But when the opportunity arises, it readily turns pathogenic, causing such life threatening infections as toxic shock syndrome, pneumonia, or sepsis. Now, a study published in the journal mBio shows that this bacterium also promotes the development of type 2 diabetes (DMII) in obese individuals.
The Last Stop for STAP
"What we are finding is that as people gain weight, they are increasingly likely to be colonized by staph bacteria—to have large numbers of these bacteria living on the surface of their skin," explained Patrick Schlievert from the University of Iowa in a press release. "People who are colonized by staph bacteria are being chronically exposed to the superantigens (SAg) the bacteria are producing.
Schlievert and his colleagues previously showed that SAgs associate with all major S. aureus infections, where they induce systemic inflammation. Since these bacteria increase significantly on the skin and nasal passages of obese individuals, and since obesity and inflammation play important roles in the development of DMII, the researchers wondered if S. aureus SAgs contributed to this process.
The team focused on the SAg toxic shock syndrome toxin-1 (TSST-1), which induces inflammatory cytokine production in adipocytes. Over the course of 6 weeks, they challenged rabbits with continuous sublethal doses of TSST-1 and monitored their ability to metabolize glucose.
After only 2 weeks, the animals began to lose the ability to respond to glucose, a condition that worsened throughout the experiment. The rabbits also showed increased insulin production, systemic inflammation, liver damage, and increased levels of circulating endotoxins.
"We basically reproduced type 2 diabetes in rabbits simply through chronic exposure to the staph SAg," Schlievert said.
After confirming increased proinflammatory cytokines and impaired glucose uptake in adipocytes removed from treated rabbits, the team recruited volunteers with DMII to see if SAg activity is reflected in human disease. They swabbed the skin of these patients, calculated the number of S. aureus present, and then extrapolated SAg exposure for each patient. By Schlievert's estimates, obese individuals are continually exposed to 1 ug of SAg, with 10-100ng SAg passing through the skin daily. Since rabbits and humans show the same susceptibility to SAgs, this quantity mirrored the exposure of the test rabbits, suggesting that SAgs may be promoting the symptoms of DMII in humans as well.
"I think we have a way to intercede here and alter the course of diabetes," Schlievert said. "We are working on a vaccine against the SAgs and we believe that this type of vaccine could prevent the development of DMII." Schlievert's group is also testing topical gels that kill S. aureas to see if reducing the number of bacteria on the skin will improve blood sugar levels in patients with pre-diabetes.
Reference
Vu BG, Stach CS, Kulhankova K, Salgado-Pabón W, Klingelhutz AJ, Schlievert PM. Chronic superantigen exposure induces systemic inflammation, elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes. MBio. 2015 Feb 24;6(2):e02554.
Bacteria May Cause Diabetes
10/02/2015 Kristie Nybo, PhD
The human microbiome has taken center stage for its roles in diseases as widely varied as malnutrition and asthma. But is it also responsible for diabetes?
Most of the time, Staphylococcus aureus lives harmlessly as a member of the human skin microbiome. But when the opportunity arises, it readily turns pathogenic, causing such life threatening infections as toxic shock syndrome, pneumonia, or sepsis. Now, a study published in the journal mBio shows that this bacterium also promotes the development of type 2 diabetes (DMII) in obese individuals.
The Last Stop for STAP
"What we are finding is that as people gain weight, they are increasingly likely to be colonized by staph bacteria—to have large numbers of these bacteria living on the surface of their skin," explained Patrick Schlievert from the University of Iowa in a press release. "People who are colonized by staph bacteria are being chronically exposed to the superantigens (SAg) the bacteria are producing.
Schlievert and his colleagues previously showed that SAgs associate with all major S. aureus infections, where they induce systemic inflammation. Since these bacteria increase significantly on the skin and nasal passages of obese individuals, and since obesity and inflammation play important roles in the development of DMII, the researchers wondered if S. aureus SAgs contributed to this process.
The team focused on the SAg toxic shock syndrome toxin-1 (TSST-1), which induces inflammatory cytokine production in adipocytes. Over the course of 6 weeks, they challenged rabbits with continuous sublethal doses of TSST-1 and monitored their ability to metabolize glucose.
After only 2 weeks, the animals began to lose the ability to respond to glucose, a condition that worsened throughout the experiment. The rabbits also showed increased insulin production, systemic inflammation, liver damage, and increased levels of circulating endotoxins.
"We basically reproduced type 2 diabetes in rabbits simply through chronic exposure to the staph SAg," Schlievert said.
After confirming increased proinflammatory cytokines and impaired glucose uptake in adipocytes removed from treated rabbits, the team recruited volunteers with DMII to see if SAg activity is reflected in human disease. They swabbed the skin of these patients, calculated the number of S. aureus present, and then extrapolated SAg exposure for each patient. By Schlievert's estimates, obese individuals are continually exposed to 1 ug of SAg, with 10-100ng SAg passing through the skin daily. Since rabbits and humans show the same susceptibility to SAgs, this quantity mirrored the exposure of the test rabbits, suggesting that SAgs may be promoting the symptoms of DMII in humans as well.
"I think we have a way to intercede here and alter the course of diabetes," Schlievert said. "We are working on a vaccine against the SAgs and we believe that this type of vaccine could prevent the development of DMII." Schlievert's group is also testing topical gels that kill S. aureas to see if reducing the number of bacteria on the skin will improve blood sugar levels in patients with pre-diabetes.
Reference
Vu BG, Stach CS, Kulhankova K, Salgado-Pabón W, Klingelhutz AJ, Schlievert PM. Chronic superantigen exposure induces systemic inflammation, elevated bloodstream endotoxin, and abnormal glucose tolerance in rabbits: possible role in diabetes. MBio. 2015 Feb 24;6(2):e02554.