# 5506
We hear a lot about the dangers of overusing, or misusing antibiotics; primarily concerns over the rise of antibiotic resistant bacteria.
This year’s World Health Day focused on antimicrobial resistance (see WHO Unveils 6-Point Plan To Preserve Antibiotic Effectiveness and World Health Day 2011), and a day hardly goes by when we don’t hear about the dangers of drug resistant staph, MRSA, NDM-1, or other Carbapenemases.
Each year tens of thousands of people succumb to resistant bacteria, and many researchers fear the day may be coming when our arsenal of antibiotics will be rendered useless.
Yet despite these dire warnings most people still expect their doctors to prescribe a course of antibiotics – even for viral illnesses which they won’t cure – because, well . . . it couldn’t hurt. Right?
Wrong.
Antibiotics, like any other medicine, are double-edged swords. They save lives, and have rightfully been called miracle drugs, but they can also cause serious side effects.
Some are well known, such as anaphylaxis (a serious, often life threatening allergic reaction). Others, like antibiotic-associated (C. difficile) colitis are probably less well appreciated by the public, despite the terrible toll this condition takes each year.
While C. diff can occasionally occur in people not on antibiotics, most of the 3 million Americans who fall victim every year are taking `miracle’ drugs like ampicillin, amoxicillin, cephalosporins, penicillin, and erythromycin.
And C. diff infection is associated with nearly 30,000 deaths each year in the United States alone.
But even less well known, and frankly, just now beginning to be explored, is what happens to our beneficial intestinal bacteria (gut flora or microbiota) after we take a course of antibiotics, and how that might affect our health.
Our intestines are home to thousands of different types of flora, including bacteria, yeasts, and protozoa.
While we don’t know all of the ways these microbiota contribute to human health, they are known to aid digestion and breakdown certain nutrients, to help produce various types of vitamins, and to have some role in our immune system.
And when you take antibiotics – even short courses – you can alter the normal ratio of these beneficial flora, and the evidence is growing that doing so can adversely affect your health.
Last year, Les Dethlefsen and David A. Relman, both researchers at the Department of Microbiology and Immunology and Department of Medicine, Stanford University School of Medicine, published a report in PNAS that looked at the adverse effects of antibiotics on gut flora.
Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation
While a limited study, these researchers examined the distal gut microbiota of three individuals over 10 months during which they received two courses of the antibiotic ciprofloxacin.
Their primary findings (from the abstract):
- The effect of ciprofloxacin on the gut microbiota was profound and rapid, with a loss of diversity and a shift in community composition occurring within 3–4 d of drug initiation. By 1 wk after the end of each course, communities began to return to their initial state, but the return was often incomplete.
- Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.
In November of 2010, Jernberg C, Löfmark S, Edlund C, Jansson JK. of the Department of Bacteriology, Swedish Institute for Infectious Disease Control published in the Journal Microbiology.
Microbiology. 2010 Nov;156(Pt 11):3216-23. Epub 2010 Aug 12.
Long-term impacts of antibiotic exposure on the human intestinal microbiota
Although it is known that antibiotics have short-term impacts on the human microbiome, recent evidence demonstrates that some impacts remain for extended periods of time. In addition, antibiotic resistant strains can persist in the human host environment in the absence of selective pressure.
Both molecular-based and cultivation-based approaches have revealed ecological disturbances in the microbiota after antibiotic administration; in particular for specific members of the bacterial community that are susceptible or alternatively resistant to the antibiotic in question.
A disturbing consequence of antibiotic treatment has been the long-term persistence of antibiotic resistance genes, for example in the human gut. These data warrant use of prudence in the administration of antibiotics that could aggravate the growing battle with emerging antibiotic resistant pathogenic strains.
All of which serves as prelude to a new study, just published in the journal Antimicrobial Agents and Chemotherapy.
0066-4804/11/$12.00+0 doi:10.1128/AAC.01664-10
L. Caetano M. Antunes, Jun Han, Rosana B. R. Ferreira, Petra Loli, Christoph H. Borchers, and B. Brett Finlay
For details we turn to the press release from the American Society for Microbiology.
Humans carry several pounds of microbes in our gastro-intestinal tracts. Recent research suggests that this microbial ecosystem plays a variety of critical roles in our health. Now, working in a mouse model, researchers from Canada describe many of the interactions between the intestinal microbiota and host, and show that antibiotics profoundly disrupt intestinal homeostasis. The research is published in the April 2011 issue of the journal Antimicrobial Agents and Chemotherapy.
"Intestinal microbes help us digest our food, provide us with vitamins that we cannot make on our own, and protect us from microbes that make us sick, amongst other things," says L Caetano M. Antunes of the University of British Columbia, a researcher on the study. In this study, the investigators used powerful mass spectrometry techniques to detect, identify, and quantify more than two thousand molecules which they extracted from mouse feces. They then administered antibiotics to the mice, to kill off most of their gut microbiota, and analyzed the feces anew.
The second round of mass spectroscopy revealed a very different metabolic landscape. The levels of 87 percent of the molecules detected had been shifted up or down by factors ranging from 2-fold to 10,000-fold.
The most profoundly altered pathways involved steroid hormones, eicosanoid hormones, sugar, fatty acid, and bile acid. "These hormones have very important functions in our health," says Antunes. "They control our immune system, reproductive functions, mineral balance, sugar metabolism, and many other important aspects of human metabolism."
The findings have two important implications, says Antunes. "First, our work shows that the unnecessary use of antibiotics has deleterious effects on human health that were previously unappreciated. Also, the fact that our gut microbes control these important molecules raises the possibility that manipulating these microbes could be used to modulate diseases that have hormonal or metabolic origins (such as inmmunodeficiency, depression, diabetes and others). However, further studies will be required to understand exactly how our microbial partners function to modulate human physiology, and to devise ways of using this information to improve human health."
(L.C.M. Antunes, J. Han, R.B.R. Ferreira, P. Lolic, C.H. Borchers, and B.B. Finlay, 2011. Effect of antibiotic treatment on the intestinal metabolome. Antim. Agents Chemother. 55:1494-1503.)
While research results obtained from mice cannot always be depended upon to translate directly to human physiology, there is a growing body of evidence linking adverse (perhaps even long-term) health effects to the use of antibiotics.
Obviously, when you are faced with a serious bacterial infection, antibiotics are a prudent, even lifesaving form of treatment.
But we should not fool ourselves into believing that antibiotics are always benign, or that there are not potential consequences from taking them.
There is a risk-reward ratio for every drug we take.
Even aspirin and NSAIDs – sold over the counter – contribute to thousands of hospitalizations and deaths each year.
Which is why taking medicines – any medicine – without a good reason can come back and bite you.
We are just now beginning to appreciate the potential side effects of antibiotic usage. Five years from now, hopefully, we’ll know a lot more.
But the evidence continues to mount that taking antibiotics inappropriately is an exceedingly bad idea.
Not only for the community around us, but for the community inside us, as well.
