THE HYPOTHESIS
Overuse of antibiotics increases the risk of obesity.
THE INVESTIGATOR
Dr. Martin Blaser, New York University Langone Medical Center.


Overuse of antibiotics has led to the creation of drug-resistant bacteria — so-called superbugs, like methicillin-resistant staphylococcus aureus. But now some researchers are exploring an equally unsettling possibility: Antibiotic abuse may also be contributing to the increasing incidence of obesity, as well as allergies, inflammatory bowel disease, asthma and gastroesophageal reflux.
Among those sounding the alarm is Dr. Martin Blaser, a professor of microbiology at New York University Langone Medical Center. In a commentary published in August in the journal Nature, he asserted that antibiotics are permanently altering microbial flora of the human body, also known as the microbiome or microbiota, with serious health consequences.
The human gut in particular is home to billions of bacteria, but little is known about this hidden ecosystem. Take Helicobacter pylori, a bacterium associated with an increased risk of ulcers and gastric cancer. Many doctors are quick to prescribe antibiotics to kill it even when the patient has no symptoms.
But in 1998, in a paper published in the British Medical Journal, Dr. Blaser was more circumspect, arguing that H. pylori might not be such a bad actor after all. “We’re talking about a bug that’s been in the human gut for at least 58,000 years,” Dr. Blaser said in an interview. “There’s probably a reason for that.”
His lab has since produced a stream of findings supporting his suspicion. Dr. Blaser and his colleagues discovered, for instance, that the stomach behaves differently after a course of antibiotics eradicates resident H. pylori.
After a meal, levels of ghrelin, a hunger hormone secreted in the stomach, are supposed to fall. But in subjects without H. pylori, the amount of ghrelin in the bloodstream held steady, in essence telling the brain to keep eating.
Moreover, mice in Dr. Blaser’s lab fed antibiotics in dosages similar to those given to children to treat ear and throat infections — which is enough to kill H. pylori in many patients — had marked increases in body fat even though their diets remained the same. (Indeed, farmers have long given antibiotics to livestock to promote weight gain without increasing caloric intake.)
These results dovetail with research by Peter Turnbaugh, a Harvard University geneticist, in collaboration with Dr. Jeffrey Gordon, a gastroenterologist at Washington University in St. Louis. They have found that the ratios of various bacteria in the guts of obese mice and obese humans were significantly different from those of lean controls, suggesting that altering the stomach’s microbial balance with antibiotics might put patients at risk for gaining weight.
Antibiotic overuse may be the root of other health problems, too. An epidemiologist at New York University, Yu Chen, has found an inverse correlation between H. pylori infection and childhood-onset asthma, hay fever and skin allergies in 7,600 participants in the National Health and Nutrition Survey.
Observation research has shown that the elimination of H. pylori actually increases the risk of gastric reflux, which is itself associated with asthma as well as esophageal diseases. Researchers in Switzerland and Germany have reported that mice given H. pylori actually are protected against asthma.
Dr. Barry Marshall, the professor of clinical biology at the University of Western Australia in Perth who was awarded the Nobel Prize in Medicine in 2005 for his part in the discovery of H. pylori and its role in gastritis and peptic ulcer disease, had a more measured reaction. “I’ve never killed anyone giving them antibiotics for H. pylori, but people have been killed who didn’t get antibiotics to get rid of it,” he said.
Patients whose internal flora are disrupt by antibiotics tend to reacquire the bugs over time, particularly if the person lives with others, Dr. Marshall said.
Nevertheless, he agreed with Dr. Blaser that antibiotics are overused and even said he foresaw a day when a detoxified strain of H. pylori might be administered as a treatment for conditions like obesity and asthma.
But wider use of antibiotics may be wreaking havoc far beyond that resulting from the loss of H. pylori. “We have so far focused on H. pylori because we have the diagnostic tests to detect it, but you could say H. pylori is an indicator organism for what is probably a vast and disappearing microbiota and increasing disease risk,” said Dr. Blaser.
The National Institutes of Health shares his concern, not only awarding him a $6.5 million grant last year to investigate the role of the disappearing microbiota in the current obesity epidemic but also allocating $115 million in 2008 to fund the Human Microbiome Project, which proposes to identify microbes that reside on and within a healthy human being.
“You can think of it as the second human genome project, where we will sequence the genes of the tremendous diversity of bacteria that populate our bodies,” said Julie Segre, senior investigator at the N.I.H.’s Human Genome Research Institute. “We will take samples from 200 healthy volunteers to get an idea of what is a normal, healthy microbiota.”
It’s an ambitious project, given that bodily bacteria outnumber human cells 10 to one. But researchers involved in the effort said advances in DNA sequencing technology make it an achievable goal. The effort is so far focusing only on microbes on the skin and in the nose, mouth, gut and genital area.
Dr. David Relman, professor of microbiology and immunology at Stanford University, said the Human Microbiome Project is important because it’s not just antibiotics that are changing the human microbiota: “Many aspects of modern life, including diet, smaller families, more hygienic practices and improved public sanitation, are affecting our bacterial communities.”
Getting a genetic snapshot of bacteria populating humans today would provide a benchmark for tracking further degradation and resulting disorders.
“We need to get an understanding of how our microbial communities operate and what to feed them so they will bloom again,” said Dr. Relman. “It’s intriguing and entirely possible that in the future we will get a cocktail of strains and species of bacteria to repair the collateral damage that antibiotics and other practices have done to our inner ecology.”
Dr. Blaser’s ideas have not always been popular, but he is gratified by the gathering interest in the human microbiome and its links to health. “I know I am now doing the most important work of my career,” he said.