Feb 25, 2013

Martin Blaser speaks about the early-life Microbiome

I like working at NYU. Interacting with very smart people has its own benefits. Even if their smarts don't directly rub off, at least I can learn something from listening to their ideas. Martin Blaser is a remarkably accomplished scientist (Past President of the Infectious Disease Society, member of the Institute of Medicine of the National Academy of Sciences, chair of the NIH Advisory Board for Clinical Research, and author of about 500 publications) with wide ranging interests in infectious disease. He has made substantial contributions to the study of Helicobacter pylori and its role in human diseases including ulcer and gastric cancer, as well as esophageal cancer, Crohn's disease and inflammatory bowel disease. Dr. Blaser has been an important contributor to the Human Microbiome Project. He has been recently profiles in the New York Times and the New Yorker magazine. Today he gave the Dean's Lecture at NYU Medical Center, where he discussed recent research in his lab on the effects of antibiotics on the microbiome of mice and the implications for human infants and children. 

Low levels of antibiotics are commonly used to supplement the feed of livestock animals, causing them to grow faster, more efficiently convert food to body mass, and to have higher levels of body fat. In a mouse system, the Blaser Lab has shown that steady low levels of antibiotics from birth to 28 weeks of age produce substantial changes in the microbe composition of the gut, as well as an increase in body fat.  The antibiotic altered microbiome, when combined with a high fat diet, has a synergistic effect on body fat (higher than either treatment alone). A similar effect is observed when several short pulses of antibiotic are administered at doses similar to what is used to treat infections in human children. The altered microbiome in antibiotic treated mice was also associated with immune suppression in the gut (lower levels of T-cells, lower levels of immune system molecules such as interleukins). 

Connecting back to human epidemiology, Americans have become much more obese in the past 50 years. In 1962, about 14% of Americans were obese, but by 2010, 42% of Americans have become obese. Blaser's point is that diet and exercise have not changed dramatically in the past generation (we ate almost as badly and were almost as lazy back in the 60's and 70's), but antibiotic use has changed dramatically.  Typical children now receive 10-20 courses of antibiotic treatments. Coincidentally, the prevalence of H. pylori in the gut has decreased  from over 50% down to just 5% of Americans.  The immune system changes that were observed in the antibiotic treated mice may correlate with the huge increases that are now observed in human asthma, celiac disease inflammatory bowel disease, type 1 diabetes, and other forms of allergy and autoimmune disorders.  Of course correlation does not prove causation, but the work of Blaser and others is beginning to identify  mechanisms that connect changes in the microbiome to these disorders. In mice, infection with H. .pylori has been shown to protect from respiratory allergic reactions.

Thanks to modern medicine, Americans now live longer, are much less likely to die of routine infections, and are taller, but we are much more obese, have more cardiac disease, and more autoimmune disease.  So, can we create a different equilibrium with our microbiome that retains the life saving anti-infection benefits of modern antibiotics, but restores the metabolic and immune balance from an earlier era?

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