Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues

111 Pages·2014·0.57 MB·English

by  Martin J. Blaser

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To my children, and to future children with a bright
future
CONTENTS
Title Page
Copyright Notice
Dedication
Epigraph
1. Modern Plagues
2. Our Microbial Planet
3. The Human Microbiome
4. The Rise of Pathogens
5. The Wonder Drugs
6. The Overuse of Antibiotics
7. The Modern Farmer
8. Mother and Child
9. A Forgotten World
10. Heartburn
11. Trouble Breathing
12. Taller
13. … and Fatter
14. Modern Plagues Revisited
15. Antibiotic Winter
16. Solutions
Epilogue
Notes
Index
Acknowledgments
About the Author
Copyright
“We live in the Age of Bacteria (as it was in the
beginning, is now, and ever shall be, until the world
ends)…”
S J G Cambridge, MA, 1993
— TEPHEN AY OULD,
13.
… AND FATTER

Why do antibiotics make animals bigger and fatter? The
goal in our study was to re-create the weight and size
increases observed in farm animals in our lab and then
tease out the principles for why they occur. It took a big
team to address these questions, but several scientists
played key roles: Ilseung Cho, a physician and a fellow in
gastroenterology; Laurie Cox, a graduate student whose
dissertation project revolved around the mouse models
and who at age fourteen had started working with
bacteria for her father’s company, which made products
for clinical bacteriology labs; and postcollege student
Yael Nobel. Without such intelligent and dedicated
trainees, I could not have tested any of my ideas. And
there were many others who joined in the quest, from
high school and college students working during the
summer to college students doing independent research
and visiting scholars from around the world.
In 2007, after a number of attempts to get the model
going, we began our first complete set of experiments on
farm practices by adding four different subtherapeutic
antibiotic treatments, which we called STAT, to the water
bottles of mice. We only looked at females because they
don’t fight as much as males, making work easier for us.
The early results were not promising; there was no
weight difference between the STAT and control mice.
When Ilseung’s research committee was told that the
mice were not gaining weight, one of our experts asked,
“What’s happening to their body composition?” He was
referring to the proportions of fat, muscle, and bone. We
didn’t know.
“Why don’t you DEXA them and find out?” he
asked.
DEXA them? The term refers to dual-energy X-ray
absorptiometry, a test given to women to determine their
bone mass and risk for osteoporosis. But DEXA also tells
us how much fat is in the body and how much muscle.
This suggestion turned out to be critical. We
discovered that all four groups of STAT mice had about
15 percent more fat than the controls, differences that
could not be explained by chance alone.
We had our first evidence that antibiotics were
changing metabolism, affecting body composition. The
STAT mice were making more fat and had about the
same amount of lean muscle as the control. We also had
an unexpected finding: at seven weeks of age, three
weeks following the start of the antibiotics, the mice were
putting on bone at an accelerated pace. More bone
formation implies that they would become bigger, longer,
and taller. But by ten weeks, all the mice had similar
bone mass. The effect on bone showed up early only in
those that were given antibiotics. In later experiments that
I describe below, we also found bone effects, some of
them lifelong. Again, this was not specific to a single
antibiotic. If it was, one might think of it as a side effect
of that one drug. But it was present across all the
antibiotics tested. This work supports the idea that, in
addition to better nutrition and clean water, antibiotics
may be part of the explanation of why people are taller
than ever.
We now had evidence that STAT changes early
development but still did not understand how it
happened. How did adding antibiotics to the water cause
these developmental effects? What made the animals
fatter and built up their bones earlier? We suspected that
the drugs changed the composition of the intestinal
resident microbes, so that is where we looked first by
examining mouse poop. Fecal pellets represent the end
product of everything that happens in the intestine and