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Vol. LXVI, No. 24
November 21, 2014
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At Kinyoun Lecture
Blaser Explores Link Between Obesity, Antibiotic Use

On the front page...

Dr. Martin Blaser gives Kinyoun Lecture at NIH.
Dr. Martin Blaser gives Kinyoun Lecture at NIH.
Evidence is mounting that the epidemic of obesity now girdling the globe might be traceable to alterations in the human microbiome introduced by widespread exposure to antibiotics, not only as medication for people but also possibly in our diet; farm animals are fattened for market with sub-therapeutic antibiotic treatment introduced in animal feed and water from an early age.

Such was the case made at this year’s NIAID Joseph J. Kinyoun Lecture by Dr. Martin Blaser, Muriel and George Singer professor of medicine at New York University Langone Medical Center. His talk, “Early Life Microbiome Influences on Metabolism, Immunity and Disease Risk,” argued that human exposure to antibiotics early in life induces permanent changes in the microbiome, with obesity being a type of changed physiology imposed by the drugs.

Continued...

Using epidemiologic data from the Centers for Disease Control and Prevention in 2010, Blaser showed the astonishing congruence in U.S. maps indicating prevalence of obesity and high use of antibiotics—they share a virtually similar geography. “There is a lot of consistency between them,” he said. “The observation is quite striking.”

Back in 1989, no state had more than a 14 percent rate of obesity among adults. By 2010, no state had a rate below 20 percent. “That’s only 21 years,” Blaser said. “Something extremely powerful must be going on to explain this.”

Data from 35 years’ worth of NHANES (National Health and Nutrition Examination Survey) studies show that obesity rates are going up progressively, beginning at ages 2-5. “The obesity epidemic is rooted at least in part in childhood,” Blaser said.

“What could be big enough to account for such a change not only in the U.S., but also all over the world?” he asked.

Blaser does not dispute that antibiotics are a major asset, “one of the miracles of modern science.” But they are being overused, he said. “Antibiotic use in the U.S. is enormous.”

In 2010, some 258 million prescriptions for antibiotics were filled, or about 833 per 1,000 people. Blaser said that, by age 20, the average American has had 17 courses of antibiotics. That doesn’t take into account fetal exposure—data show that 50 to 60 percent of pregnant women in the U.S. take antibiotics.

Blaser cited a CDC study conducted in 2014 by Dr. Lauri Hicks and her colleagues that tied the highest antibiotic prescription rates to America’s poorest counties.

“The poorest people, and the least educated people, appear to be getting the most antibiotics,” said Blaser. “That’s something that hasn’t been observed before and is perhaps part of the puzzle as to why obesity is seen so much in poor people.”

Antibiotic use in livestock is also an important part of the story, he said. “Most antibiotics used in the U.S. are used on the farm.”

During the 1940s, farmers found that adding sub-therapeutic doses of antibiotics to feed and water promoted livestock growth. It was later discovered that “it works from chickens to cows, and with any anti-bacterial agent you use,” Blaser said. “The younger in life [the animals] start the antibiotics, the more profound the effect on growth rate and feed efficiency.”

NIAID’s Dr. Steve Holland asks a question at the Kinyoun Lecture. Blaser fielded an unusually robust round of questions following his talk. NIAID director Dr. Anthony Fauci introduced Blaser, noting that Blaser’s recent book—Missing Microbes—is a good read. “I hope I’m not breaking any ethics rules by saying that,” Fauci quipped.

NIAID’s Dr. Steve Holland asks a question at the Kinyoun Lecture. Blaser fielded an unusually robust round of questions following his talk.

Photos: Bill Branson

NIAID director Dr. Anthony Fauci introduced Blaser, noting that Blaser’s recent book—Missing Microbes—is a good read. “I hope I’m not breaking any ethics rules by saying that,” Fauci quipped.

Blaser reviewed data from 8 studies in mice that were fed antibiotics in his laboratory. Research showed that antibiotics: change body composition, including microbiota; promote the metabolic syndrome (a disorder of energy use and storage that can lead to obesity, high blood pressure, diabetes and heart failure) and fatty livers; and down-regulate genes governing immunity.

“There is an early developmental window,” said Blaser, “where, with perturbation of the microbiota, even if it returns essentially to normal [by withdrawing antibiotics], the effect is lifelong.”

He said that type 1 diabetes, like obesity, is also increasing around the world, “doubling about every 20 years.” That observation is borne out in the mouse model—early life administration of antibiotics fuels type 1 diabetes in mice.

From animal studies, Blaser returned to human epidemiologic studies. One such study, of early life microbiome disruption, conducted on 10,000 children in the 1990s, showed that early antibiotic use was associated with adiposity.

Cesarean birth, which deprives newborns of full exposure to the mother’s microbiome, is associated with more adiposity later in development, Blaser said. At the instant of birth, he explained, a newborn’s passage through the birth canal bathes a child in its mother’s vaginal microbiota, some of which is swallowed. This confers an irreplaceable metabolic and possibly immunologic advantage to the baby. But 32 percent of U.S. births occur by C-section, and the number is rising, he said. At a time when the microbiome is at its most dynamic (up to age 3), modern medical practice is short-circuiting a developmental process nature has spent eons perfecting.

Blaser cited two more studies: One, published in JAMA Pediatrics just a week earlier, showed that, among 65,000 children in Atlanta ages 2-5, antibiotic exposure increased risk of obesity. The other, conducted in Denmark over 10 years, linked increased antibiotic use to higher risk of inflammatory bowel syndrome, especially Crohn’s disease.

He concluded his talk with several recommendations:

  • Use antibiotics on the farm only to treat illness.
  • Increase research about the consequences of antibiotic use in humans.
  • Educate the public and professions about risks of antibiotic exposure.
  • Use narrow (vs. broad) spectrum treatments. He said that we need to develop new narrow-spectrum agents and new diagnostics.
  • Pursue remediation by replacing acutely lost actors (“scientifically developed probiotics, not the kind marketers promote”) and enhancing depleted actors (prebiotics).
  • Pursue reversal by archiving vanishing organisms and replacing disappeared organisms and pathways.
  • Monitor whether interventions are working.

Blaser called recent FDA regulations on antibiotic use in farm animals, which are voluntary, a “baby step” in the right direction, and hopes they will be enforced in order to “diminish our assault on the microbes of our domesticated animals.”

He predicts a new algorithm for child health based on analysis of a newborn’s filled diapers: “What are the microbes they have that are globally important? If they’re lacking, we can administer them.”

Blaser’s full talk can be seen at http://videocast.nih.gov/summary.asp?Live=14598&bhcp=1.


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