Superbug risk to children given too many Antibiotics , killing bacteria that fight disease
‘Generation is important,’ he said. ‘A woman born in the 1940s might have two courses of Antibiotics in childhood. If she has a daughter, she might pass on slightly fewer normal bacteria. Her daughter will likely have several courses of Antibiotics and the granddaughter has slightly fewer bacteria again. ‘Each generation could be beginning life with a smaller endowment. ‘I am not saying not to give antibiotics to people with serious illnesses. But if what we suspect is proven, doctors need to look more closely at risk and benefit.’
The loss of the “invisible zoo inside of us” may be linked to a host of chronic illnesses on the rise, an idea that’s still widely considered to be almost heretical. How is your research being received? The very good news is that our work is getting a great reception after being in the wilderness for many years. As a scientist, what you want to do is to make a difference and for your ideas to be converted into action. That’s one of the reasons I wrote the book; there are costs to antibiotics. Do you think doctors might resent their patients questioning treatment that includes antibiotics? All the incentives are to prescribe, and the patient thinks if they’re not given an antibiotic, they’re at risk. I want to change the dialogue. The doctor will say, “According to the latest research... there is an increased risk for asthma or obesity.” The doctor will be more cautious and the patient will be more cautious. It can be done if we change our culture.
In a provocative editorial published this week in Nature, Martin Blaser of New York University’s Langone Medical Center argues that antibiotics’ impact on gut bacteria is permanent — and so serious in its long-term consequences that medicine should consider whether to restrict Antibiotic prescribing to pregnant women and young children.
Early evidence from my lab and others hints that, sometimes, our friendly flora never fully recover. These long-term changes to the beneficial bacteria within people’s bodies may even increase our susceptibility to infections and disease. Overuse of antibiotics could be fuelling 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.
Among the findings he cites in support: The population-level observation that the incidence of infection with H. pylori, the bacterial cause of gastric ulcers, has declined over decades just as the incidence of esophageal cancer has risen. In addition, he offers his own research group’s observation that children who don’t acquire H. pylori are at greater risk of developing allergy and asthma, and their findings that eradicating H. pylori affects the production of the two hormones, ghrelin and leptin, that play a role in weight gain.
Are antibiotics to blame for the decline in H.pylori? Blaser points out that the organism is vulnerable to the same antibiotics that are prescribed to children for ear infections and colds — and that children routinely receive up to 20 courses of antibiotics before they reach adulthood. In addition, he says, one-third to one-half of women in the industrialized world receive antibiotics during pregnancy. Couple that with the increasingly large percentage of children born by Caesarean section — who by skipping their trip through the birth canal miss their first exposure to friendly bacteria — and the result, he says, is that “each generation… could be beginning life with a smaller endowment of ancient microbes than the last.”
Finally, he points to evidence that Antibiotic use permanently changes the composition of the gut microbiome, altering the balance of bacterial species and maintaining resistant bacteria in the gut.
The function and influence of the microbiome — in the gut, on the skin and everywhere in the body — is a huge research issue right now, with the founding by the National Institutes of Health of the Human Microbiome Project, not to mention continuing debates over the accuracy of the “hygiene hypothesis” and speculation that altering gut flora could influence everything from obesity to depression. This proposal dovetails with those inquiries — and also (you knew I had to get there eventually) with ongoing concern about Antibiotic over-use encouraging the emergence of resistant organisms.
The human body contains 10 times more bacteria than human cells, with 50 trillion microbes living in the average digestive tract alone. The study of these internal bacteria is in its infancy: the Human Microbiome Project, launched to catalogue our bodies’ bacterial inhabitants, started last October.
All these microbes are not just along for the ride, say scientists, but have co-evolved with human beings, providing important biochemical services in exchange for their home. Imbalances in gut bacteria have already been linked to obesity, cancer, asthma and a host of autoimmune diseases.
Though marketers of what are known as probiotics have had some success in using bugs to treat allergies and irritable bowel disease, the causal links between bacteria and disease remain largely unspecified.
"If you want to use bacteria in an intelligent way, you really need to know what affect bacteria have on the biochemistry of a person," said Wikoff.
A critical first step in figuring them out is linking bacteria to cellular processes, known broadly as metabolites. The study of metabolites is also just getting off the ground. Some are cellular byproducts, while others are physiologically critical. But though the first draft of the human metabolome — the biochemical analogue of the human genome — was completed just two years ago, scientists know it’s important.
In the new mouse comparison study, published Monday in the Proceedings of the National Academy of Sciences, some metabolites were found only in germ-free mice. Others were found only in regular mice. Some were found in both, but in subtly different forms. The hodgepodge of results suggests that various bacteria break down, produce or otherwise tweak biochemicals.
The study "provides evidence of the profound effects of the microbiome on mammalian metabolism," said New York University microbiologist Martin Blaser. "Although the study was done in mice, the conclusions are largely generalizable to humans."
Wikoff’s team didn’t concentrate on specific metabolites, but a few stood out. Levels of the mood-regulating transmitter serotonin were altered, as were metabolites involved in processing drugs. The latter finding suggests that gut bacteria could be involved not just in maintaining health and disease, but processing drugs — helping to explain, perhaps, why drugs affect people in different ways.
Another tantalizing find in the bacteria-rich mice was indole-3 propionic acid, an antioxidant thought to have potential in treating Alzheimer’s.
As the microbiome and metabolome projects continue, the links are likely to become clearer.
"What we’ve done here is just a first step," said Wikoff.
Citation: "Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites." By William R. Wikoff,
Andrew T. Anfor, Jun Liu, Peter G. Schultz,1, Scott A. Lesley,
Eric C. Peters, and Gary Siuzdak. Proceedings of the National Academy of Sciences, Vol. 106 No. 6, Feb. 9, 2009.
A new study shows that the presence of Clostridia, a common class of gut bacteria, protects against food allergies in mice, suggesting that probiotic therapies could be developed to treat people with similar food sensitivities .