Editorial: “Antibiotics are wonder drugs no more“
THE trillions of bacteria that colonise our guts are in jeopardy. Overusing antibiotics has not only led to the development of dangerous superbugs, but has changed the bacteria that live inside us. Now evidence suggests that new gut floras may be responsible for our expanding waistlines.
Antibiotic use has been rising for the past 70 years. They are now often prescribed as a precaution for illnesses when the cause has not been confirmed as a bacterial infection. , a microbiologist at New York University, fears that over-prescribing antibiotics could be harming some communities of “good” bacteria that line your intestines.
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The effects could be long-lasting, too. For example, some antibiotics seem to permanently oust Helicobacter pylorifrom their home in our stomachs. Widespread use of antibiotics has correlated with a fall in the number of people playing host to H. pylori. That might seem like good news since the bug has been linked to stomach cancer and gastric ulcers, both of which have become less common. However, these positive outcomes coincide with a surge in cancers of the oesophagus, attributed to the more acidic environment H. pylori leaves behind when it vacates the stomach (Nature Reviews Microbiology, ).
To investigate whether overusing antibiotics could also play a part in the rise of obesity, Blaser’s team fed infant mice low doses of penicillin to mimic doses given to farm animals. After 30 weeks, penicillin-fed mice were between 10 and 15 per cent bigger and twice as fat as drug-free mice.
When the team looked at the mice’s gut bacteria, they found that the antibiotic-fed mice had a different complement of bugs to the untreated mice. Low doses of antibiotics had seemingly shifted the balance of certain gut microbes, reducing the numbers of Lactobacillus, which is a “good” bacterium linked to a .
To confirm that the mice owed their supersize to an altered gut microbiome, the group turned to germ-free mice, which are bred in a sterile environment and have no gut bacteria. Within five weeks of being given gut bacteria from the mice fed antibiotics, the once germ-free mice were 35 per cent larger than mice with a regular microbiota.
In the initial experiment, the biggest mice were those that had started antibiotic treatment from birth. Even mice that were only given drugs for four weeks ended up as large as mice on antibiotics for the full 30 weeks. This suggests that gut flora may be most vulnerable to disruption in the earliest moments of life, says Blaser.
Antibiotics used to treat children may also have a detrimental effect on their immune systems, says Blaser. In a separate study in mice, his team mimicked the short courses of higher dose antibiotics that young children tend to receive for infections. The group then investigated whether these pulsed doses were having any effect on helper T-cells – a group of immune cells that secrete chemicals to direct the immune response. They found that the levels of these chemicals were significantly lower in antibiotic-fed mice, suggesting that their immune systems may have become compromised. Blaser presented his findings at the in Paris, France, last week.
Although no one yet knows why certain groups of bacteria may affect weight, Blaser says that we might expect young children exposed to antibiotics to gain weight like the mice. Indeed, similar effects have already been spotted in humans: when and her colleagues at Copenhagen University Hospital in Denmark followed the development of 28,000 babies, they found that those given antibiotics within the first six months of life were more likely to be overweight at age 7, even if their mother had a healthy weight (International Journal of Obesity, ).
“Babies given antibiotics during the first six months of life were more likely to be overweight at age 7”
What’s more, the problem could get even worse for future generations, Blaser says. We think babies first acquire bacteria during birth, when they travel through their mother’s vaginal canal or are exposed to hospital environments. A newborn girl treated with antibiotics could grow up with an altered microbiome, and be unable to provide her own children with the missing bacteria.
Blaser is not the only one to be concerned. at the University of Washington in St Louis, Missouri, says it could well be true that antibiotics are contributing to soaring obesity rates. “The pulses of antibiotics really reflect what children are given [in real life],” she says.
A recent study of 3000-year-old human faeces suggests that the make-up of our microbiomes has changed (see “Look to ancient faeces for obesity cure”). To protect ourselves from disease, we may want to repopulate our guts with the bacteria we evolved with, says Blaser. The best places to investigate the role of bacteria are poorer countries with limited access to antibiotics, he adds. “You’d have to go to developing countries and start hoovering up faeces,” says at the University of British Columbia in Vancouver, Canada.
“Microbes are not accidental – we have co-evolved with them,” says Blaser. “They are useful, but they are changing as a result of lifestyle, and this is changing our disease risk.” The answer isn’t to stop giving antibiotics, he says. “A lot of what we have to do is research. We need to narrowly treat infections. We need better diagnostics and better therapeutics.”
Look to ancient faeces for obesity cure
If antibiotics are ruining our gut flora, and consequently promoting obesity (see main story) how can we make it right again? One idea is to repopulate our depleted intestines with ancient bacteria, says at New York University. and his colleagues at the University of Oklahoma in Norman are starting to get a pretty good idea of what these ancient bacteria might be, after studying fossilised faeces.
Curious to see what a prehistoric microbiome – the collection of bacteria lining our intestines – might have looked like, Lewis and his colleagues collected ancient faeces from soil in caves and directly from the intestines of mummies around North and South America. All of the samples were between 1400 and 3000 years old.
The team then extracted DNA before comparing its bacterial make-up to known microbiomes of modern Americans, rural African children, primates including chimps and gorillas, and the Tyrolean iceman Öٳ, who lived around 5000 years ago.
Lewis’s team was able to piece together microbiomes for each of the samples. “They do appear to be different,” he says. Surprisingly, though, the ancient faeces have more bacterial DNA in common with those of non-human primates and children living in rural Africa than they do with modern, western gut microbiomes. “My first hypothesis would be that chlorinated water and antibiotics fundamentally changed human microbiomes,” says Lewis, who presented the findings at the in Paris, France, last week.
“The association between antibiotics and obesity is important to explore,” he says. So, should we be repopulating our guts with missing bacteria? “It’s too early to tell if that’s a good idea,” says Lewis. “However, it is certainly an important idea that requires investigation.”
