Antibiotics and Obesity

“We’re finding that the microbiome is affected not just by age and antibiotics, but how many plants you eat, how much alcohol you drink, how much you exercise and how much sleep you get on average,” says microbiologist Rob Knight, the project’s co-founder.

Does fat run in your family?

Blame your gut bacteria.

Researchers at Cornell University have identified a family of microbes called Christensenellaceae that appear to help people stay lean—and having an abundance of them, or not, is strongly genetic.

Someday, it may be possible to have the Christensenellaceae clan adopt you, however. Mice that received transplants of the bacteria gained less weight than untreated mice eating the same diet. The study was published in the journal Cell this month.

There has been an explosion of research into how bacteria affect human health, and body weight is one of the most intriguing areas. There is growing speculation that rising rates of obesity may be due in part to increased use of antibiotics, which may be wiping out bacteria that help humans convert food into energy efficiently.

Babies are born without any bacteria and eventually play host to approximately 100 trillion of the tiny micro-organisms, which outnumber human cells by about tenfold. Bacteria coat every inch of skin, the mouth, the nose, the ears, the genitals and particularly the gastrointestinal track. They not only digest food and help fight off invaders, but also produce vitamins and chemicals that help regulate the immune system, metabolism—even mood.

Microbiologist Rob Knight, center, with colleagues sampling oral bacteria from a graduate student at the Knight Lab at the University of Colorado at Boulder. AMERICAN GUT PROJECT

“In the past, the main bacteria we saw were the nasty guys, the ones that kill you. We haven’t been looking at the thousands of nice guys that help us and keep us thin,” says Tim Spector, a genetic epidemiologist at King’s College London, who also contributed to the study.

This microbiome, as it is called, has evolved along with humans, and even small disruptions have been implicated in a long list of health problems, including obesity, diabetes, high blood pressure, abnormal cholesterol, belly fat, cancer and atherosclerosis, or plaque buildup in the arteries.

The field is booming in part because scientists are now able to identify and count bacteria more easily, using gene analysis, in stool, saliva, and other samples. The collections can provide a bonanza of information of how complex and different human bacteria communities are.

Introducing bacteria into mice raised to be virtually germ-free has allowed scientists to demonstrate not correlations, but actual cause and effect.

It has been known for decades that gut bacteria affects weight in animals. Farmers have been giving antibiotics to livestock and poultry since the 1950s because it makes them grow fatter, says Martin Blaser, a microbiologist at New York University. His studies have shown that giving low-dose penicillin to mice for just four weeks early in life makes them obese later in life—even when their gut bacteria appeared to be normal.

The proliferation of antibiotics, antibacterial soaps and other products isn’t just creating some resistant strains, but decimating the bacteria population that humans have evolved with, Dr. Blaser writes in his new book, “Missing Microbes.”

GETTING TO KNOW YOUR MICROBIOME

Among the most common bacteria researchers find:

  • Bifidobacteria is transferred in breast milk and may prevent tumors.
  • Christensenella guards against obesity, and runs in families.
  • Helicobacter pylori causes peptic ulcers but helps regulate appetite.
  • Escherichia coli produces vitamin K, but can cause severe illness.
  • Clostridium difficile causes colitis, diarrhea and can be deadly.
  • Staphylococcus aureus causes boils, MRSA and is drug-resistant.
  • Pseudomonas aeruginosa causes ear and eye infections, and can spread in hospitals.

He is particularly concerned that a type of bacteria that helps regulate appetite is disappearing from human GI tracts. The Helicobacter pylori is notorious for causing peptic ulcers, but studies show that it also helps regulate ghrelin, the hormone that increases appetite. Without H. pylori to keep ghrelin in check, humans may miss the natural signals that tell them to stop eating. Yet only about 6% of U.S. children harbor the bacteria in measurable amounts.

“We humans are changing,” says Dr. Blaser. He says Americans today have only about two-thirds the number of bacterial species as native tribesman in the Amazon that have been exposed to fewer antibiotics.

Other studies have shown that in mice, at least, altering gut bacteria alone can change body weight, regardless of diet and exercise levels. In a study published in Science last year, researchers at Washington University in St. Louis harvested gut bacteria from four sets of identical twins in which one was lean and one was obese, and transplanted them into mice that were raised germ-free. Within weeks, the mice matched with obese donors became obese, while those with lean donors stayed lean—despite eating the same low-fat food.

The new Cornell study is one of the first to show that genetics plays a role in the bacteria that regulate weight gain.

The researchers analyzed stool samples from nearly 1,000 people ages 23 to 86, including 416 pairs of twins. Levels of the little-known Christensenellaceae bacteria were more similar in the identical twin pairs than the fraternal pairs, indicating genetics have a strong influence. The Christensenellaceae were more abundant in the lean twins than the obese twins.

The researchers transplanted the bacteria into germ-free mice, which weighed significantly less than untreated mice after 21 days.

As of now, scientists don’t know how Christensenellaceae affects human metabolism or even how it is inherited. The speculation is that human genes affect which bacteria flourish and which dwindle—much like seeds fare better or worse in different soil.

Next, the Cornell researchers plan to give the Christensenellaceae bacteria to mice orally (rather than in a fecal transplant) and study how long the effect lasts, which could pave the way for a human probiotic version. Is that likely someday? “I’m a scientist—I’m going to say, maybe,” says microbiologist Ruth Ley, the study’s senior author.

More research into the role bacteria play in health is under way as part of the Human Microbiome Project at the National Institutes of Health. “We are just at the very beginning of this field,” says program director Lita Proctor.

One study funded by the project is looking at what changes occur in the microbiome of pregnant women as birth approaches; another is tracking how stresses such as a divorce, job loss or bout of the flu may alter the gut bacteria in people who are pre-diabetic and possibly trigger full-blown Type II diabetes.

Scientists are also hoping to learn more about human bacteria through crowdsourcing. To date, about 7,000 people have sent stool or saliva samples to the American Gut Project, based at the University of Colorado, along with information about their diet, health and lifestyle habits. For $99 and up, donors get a statistical profile of their microbiome—and researchers get a wealth of data to explore.

“We’re finding that the microbiome is affected not just by age and antibiotics, but how many plants you eat, how much alcohol you drink, how much you exercise and how much sleep you get on average,” says microbiologist Rob Knight, the project’s co-founder.

A British version began last month. Some volunteers are joining pilot studies to see how much they can alter their gut bacteria by changing their diet for three days. “I did one eating masses of unprocessed cheese,” says Dr. Spector, who founded British Gut. It didn’t change his gut bacteria significantly, he says, “but it put me off cheese for a bit.”

Most microbiologists say the legions of yogurts, smoothies, supplements and other products packed with “probiotics” on the market are probably harmless, but largely untested and unregulated with little evidence to back up the claims.

Write to Melinda Beck at HealthJournal@wsj.com

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