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article imageEssential Science: Health effects of antibiotic use

By Tim Sandle     Nov 23, 2015 in Science
A disturbing, newly issued report suggests just one single course of antibiotics can disrupt the microbial composition in the gut sufficiently to trigger a spate of unintended ill-health effects. Digital Journal gets to the bottom of the issue.
Antibiotics and antimicrobials have been in the news recently, particularly the misuse of antibiotics (such as adding the drugs to farm animal feed), to the growing threat of antimicrobial resistance by certain pathogens (so that many infections that were commonly treatable are no longer so); and with the difficulties in finding new candidate substances as the basis for active ingredients for a new generation of antimicrobials. Such searches are important given the news about the discovery of bacteria resistant to drugs like colistin, which are used when all other treatments have failed.
As an example of the extent of antibiotic prescribing, taking the case of the U.K., figures released by Public Health England show total antibiotic consumption (daily dose of antibiotics per 1000 inhabitants per day) has increased by 6.5 percent since 2011. Most of this increase has come about through prescriptions administered to people in hospital.
These issues have been extensively covered on Digital Journal's science and health pages.
Now a new problem is being discussed: the effect that even a single course of antibiotics can have on the microbiome (the totality of microorganisms and their genetic interactions) in the gut. This disruption is linked with a range of ill-health effects.
The risks to patient health are demonstrated in a study published in the journal mBio. The research described two randomized, placebo-controlled trials of healthy people. A single course of oral antibiotics, given to one of the study groups, led to a significant alteration to the composition and diversity of microorganisms found in the gut. The effects continued for several months, and, with a small number of the study group, continued for one year. As well as looking at the gut, the study extended to an examination of the typical organisms found within the mouth.
For the study, 66 people were examined (29 from Sweden and 37 from the U.K.). The patients were divided into two groups, according to the research summary. One group was given a placebo and the other a common antibiotics. The antibiotics were varied. The Swedish subjects were either given lincosamide (generic name: clindamycin) and a quinolone ((generic name: ciprofloxacin); and the U.K. participants were administered tetracycline (generic name: minocycline) and a penicillin (generic name: amoxicillin). With each antibiotic, a standard course was given.
Before the studies began the typical microorganisms, from fecal and saliva samples, were assessed using genetic sequencing (16S rRNA gene amplicon sequencing.) Throughout the course of antibiotics and afterwards, microbial assessment continued so the change in microbial composition could be accurately profiled. Such testing continued for 12 months. In all, 389 fecal and 391 saliva samples were tested.
Resistance to drugs emerges through changes in a bacterium's genetic code -- altering the targe...
Resistance to drugs emerges through changes in a bacterium's genetic code -- altering the target on its surface to which antibiotics would normally bind, making the germ impenetrable or allowing it to destroy or "spit out" the antibiotic
Jorge Dirkx, BELGA/AFP/File
Each of the antibiotics led to the same effect: the gut microbiota was altered. Troublingly, the antibiotic treatments caused a spike in genes associated with antibiotic resistance.
In terms of differences between the antibiotics, clindamycin led to a loss of microorganisms capable of producing a short-chain fatty acid (called butyrate ) that can inhibit inflammation, carcinogenesis, and oxidative stress in the gut. This was the clearest example of a link between gut microbial changes and health effects.
The risk here is that although the antibiotic may succeed in eliminating the pathogen of concern; drastic shifts in the gut flora mean that other pathogenic infections become more likely. This is because many instances of pathogenic infection are kept in check through competition with beneficial bacteria. in short, the non-harmful bacteria outgrow those that are potentially pathogenic.
So far, the effects relate to the composition of the gut. Research suggests other regions of the body towards which antibiotics are targeted, such as the mouth, are more robust and the natural microbiome is fairly rapidly restored.
The authors of the study, led by scientists based at the University of Amsterdam, said while much attention has been paid to antimicrobial resistance there has been too little study about the disruptive effects antimicrobials can impart on the bacteria that reside within the body. A raft of studies suggest the composition of the human microbiome plays an important part with health and disease.
In relation to this, lead study author Egija Zaura, PhD, an associate professor in oral microbial ecology at the Academic Centre for Dentistry in Amsterdam, the Netherlands, told the American Society for Microbiology: " My message would be that antibiotics should only be used when really, really necessary. Even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome.”
The important mBio article is titled "Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces."
In related news, a different research group found, from a mouse model, that beta lactams antibiotics caused the Staphylococcus aureus bacteria to produce cell walls that had inflammatory properties, which caused tissue damage. This meant that while the pathogen can be killed with antibiotics, the such antibiotics appear to trigger biochemical changes to the bacterial cell wall that can harm the body.
Under a very high magnification of 20 000x  this scanning electron micrograph (SEM) shows a strain o...
Under a very high magnification of 20,000x, this scanning electron micrograph (SEM) shows a strain of Staphylococcus aureus bacteria taken from a vancomycin intermediate resistant culture (VISA).
CDC / Janice Haney Carr
This article forms part of Digital Journal's Essential Science series, providing readers with analysis of the key science stories climbing high up the global news agenda.
More about antibiotic health, Antibiotics, antimicrobials, Children, Guts
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