Overuse of Antibiotics Is Seen Behind Many Human Ills
You were not meant to be alone: The human body contains and is covered in an almost unimaginably large number of microbes. But eradicating them as we do, intentionally and unintentionally, with the prolific use of antibiotics may be harming our health, according to one scientist who studies our minuscule companions.
"Overuse of antibiotics could be fueling the dramatic increase in conditions such as obesity, type 1 diabetes, inflammatory bowel disease, allergies and asthma, which have more than doubled in many populations," writes Martin Blaser, a professor of microbiology and chairman of the department of medicine at New York University Langone Medical Center.
Humans are sometimes called meta-organisms, because of the sheer number and volume of microbes that share our bodies — living in our guts, on our skin, even in our belly buttons. Evidence is building for the benefits these healthy microbial communities offer us. They help us access nutrients, such as vitamin K, and energy from complex carbohydrates. They deter dangerous infections, and recent evidence indicates they help keep at bay multiple sclerosis and other autoimmune disorders. [5 Wacky Things That Are Good for Your Health]
Antibiotics are nothing short of miracle drugs, and they share the credit for extending the life expectancy from 63 for a U.S. citizen born in 1940 to 78 for someone born in the U.S. today, noted Blaser in his commentary, published in the Aug. 25 issue of the journal Nature
One problem with the overuse of antibiotics has received fairly widespread attention: the selection for drug-resistant bugs. But Blaser points out a lesser-known effect: These medications, along with other changes in how we live, are altering the communities of microbes that share our bodies.
For example, one study published in 2010 monitored how three people's gut bacteria responded to two courses of the antibiotic ciproflaxin. The antibiotic, the researchers found, caused rapid and profound changes in the microbe populations, which never fully returned to their initial state. Other research has shown that antibiotic-induced changes, including the arrival of antibiotic-resistant microbes, can last for at least three years.
For 26 years, Blaser has worked with the bacterium Helicobacter pylori. Discovered in 1982 by Robin Warren and Barry Marshall, who later shared a Nobel Prize for the discovery, the bacterium is linked to stomach inflammation, ulcers and gastric cancer.
Over time it became clear, however, that the bacterium has an ancient relationship with humans and that it is disappearing from our guts — by the turn of the 21st century, fewer than 6 percent of children in the U.S., Sweden and German were carrying the microbe, according to Blaser.
Not surprisingly, gastric cancers and ulcers have become less common. However, diseases of the esophagus, including esophogeal cancer and acid reflux, have increased dramatically at the same time, and it turns out there is an inverse relationship between these diseases and the presence of H. pylori, which seems to protect the esophagus. And people who lack the bacterium are more likely to develop asthma, hay fever or skin allergies as children, Blaser and colleagues found.
Signaling to our immune systems
It's clear that resident microbes play a role in our health, although scientists are still exploring the scope of their impact on our biological systems such as metabolism and immunity, according to Dennis Kasper, a professor of medicine and microbiology and immunology at Harvard Medical School, who did not contribute to Blaser's commentary.
It's well known that antibiotics can enable the bacterium Clostridium difficile, already present in some healthy people, to cause colon-inflaming infections by decimating the other, healthy microbes in humans, Kasper said.
However, most evidence so far comes from work done experimentally on mice and other animals. For example, so-called germ-free mice, which lack the normal healthy microbes, are more susceptible to infections by the food poison bacterium Salmonella than mice with the normal bacterial complement, according to Kasper.
Research is showing that resident microbes play a complex role in keeping us healthy. For instance, certain gut residents stimulate different sets of T-cells, a type of white blood cell that either promotes or reduces the inflammation associated with an immune response.
"We have very complex flora that, in a healthy situation, seems to keep pro-inflammatory and anti-inflammatory T-cells in balance with each other," Kasper said. An imbalance between these subsets of immune cells can make someone more susceptible to immune-mediated diseases like inflammatory bowel disease and multiple sclerosis or their flare-ups, he said. [Why Are Humans Always So Sick?]
In these diseases, the body's immune system attacks part of itself —the intestinal tract in instances of inflammatory bowel disease; the covering on the nerves in cases of multiple sclerosis. So certain bacteria appear to help prevent this.
In his lab, Kasper and colleagues are looking at a molecule produced by a gut microbe called Bacteriodes fragilis. This molecule stimulates the inflammation-suppressing T-cells. Working with mice, they have shown that the toll of experimental inflammatory bowel disease and a disease similar to multiple sclerosis can be substantially reduced if this molecule is fed to the animals.
"The gut may hold many molecules that have these kinds of effects on the immune system," he said.
Restoring our microbes
Blaser suggests a more-judicious use of antibiotics, as well as the development of techniques to rapidly identify the problem pathogen and drugs that target only specific pathogens while leaving other microbes unharmed.
We may also need to actively replace what we have lost. Probiotics — microbes consumed for their beneficial qualities — have promise, although the science is only in its earliest stages, he said.
These might be used one day in conjunction with antibiotic treatment to maintain healthy communities, or administered alongside vaccinations to replace communities we have lost, according to Blaser.
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