From: logic23x@gmail.com   
      
   Repeated antibiotic use alters gut's composition of beneficial microbes, study   
   shows    
      
   SEP 13 2010    
   David Relman    
      
      
   Repeated use of an antibiotic that is considered generally benign, because   
   users seldom incur obvious side effects, induces cumulative and persistent   
   changes in the composition of the beneficial microbial species inhabiting the   
   human gut, researchers at    
   the Stanford University School of Medicine have found.    
      
   By a conservative estimate, something like 1,000 different varieties of   
   microbes coexist harmoniously within a typical healthy person’s gut, said   
   David Relman, MD, professor of medicine and of microbiology and immunology at   
   the medical school and chief    
   of the infectious diseases division at the Veterans Affairs Palo Alto Health   
   Care System. Relman is the senior author of a paper, published online Sept. 13   
   in Proceedings of the National Academy of Sciences.    
      
   The study examined the effects of ciprofloxacin (trade name Cipro), an   
   antibiotic that is widely prescribed for intestinal, urinary and a variety of   
   systemic infections. In an earlier, short-term study, Relman’s group had   
   concluded that people’s    
   intestinal microbial communities seem to bounce back reasonably well within   
   weeks after a five-day regimen of ciprofloxacin. This new study involved two   
   courses of antibiotic administration, six months apart, and it revealed   
   more-subtle, long-term    
   effects of ciprofloxacin use — such as the replacement of multiple resident   
   bacterial species by other, closely related varieties and the occasional   
   complete eradication of a species.    
      
   The infrequent occurrence of easily visible side effects such as bloating and   
   diarrhea from ciprofloxacin use has given rise to an assumption that the drug   
   spares most beneficial gut-dwelling bacteria. Overall similarities between   
   pre-regimen gut    
   bacterial strains and their post-regimen replacements explain why such side   
   effects aren’t typically seen after ciprofloxacin use. Still, the more   
   nuanced differences between the pre-existing communities and those that appear   
   in the wake of this    
   repeated disturbance present a new set of problems, said Relman, who is also   
   the Thomas C. and Joan M. Merigan Professor at the medical school. A bacterial   
   species whose presence was lost or diminished may have been performing a   
   valuable job — for    
   example, secreting a protein that’s toxic to a particular pathogen — that   
   is shirked by its replacement. The abandoned function might not be noticed   
   until, perhaps, years later when the pathogen in question invaded the   
   person’s gut.    
      
   While the study’s findings shouldn’t be interpreted to mean that   
   ciprofloxacin is dangerous and should be avoided, Relman said, they do raise   
   questions about possible long-term effects of antibiotic administration, in   
   addition to concerns about    
   spurring the evolution of drug-resistant organisms. The new findings   
   underscore the desirability of finding ways to pinpoint not just which   
   bacteria have been lost or whose numbers were diminished by an antibiotic, but   
   also which important beneficial    
   functions performed by the patient’s gut microbial community as a whole have   
   been impaired — such as signaling cells of the intestinal lining, which are   
   constantly turning over, to maintain an appropriate barrier against ingested   
   toxic compounds, or    
   secreting anti-inflammatory substances that may prevent allergic or autoimmune   
   diseases.    
      
   For this study, the Stanford scientists collected more than 50 stool samples   
   from each of three healthy adult females over a period of 10 months. Then they   
   used advanced, molecular techniques to count the number of different microbial   
   species represented    
   in each sample, as well as relative population sizes of the different species   
   in that sample.    
      
   Twice during this 10-month period, the researchers perturbed their subjects’   
   gut ecosystems by giving them five-day courses of ciprofloxacin at a standard   
   dose. During the first course, overall bacterial populations in each subject   
   — which had    
   previously waxed and waned but, on the whole, been quite stable — plummeted   
   and remained depressed for about a week. Roughly one-third to one-half of the   
   resident species’ populations declined, with some disappearing entirely. A   
   few originally less-   
   abundant species grew in number, as they filled in the ecological niche   
   abandoned by bugs adversely affected by the drug.    
      
   Within a week after the first course’s completion, two of the three   
   subjects’ internal microbial ecosystems had largely returned to a state   
   fairly similar to that before the regimen, as measured by the broad classes to   
   which the microbial    
   constituents belonged. One subject’s overall ecosystem, however, still had   
   not recovered even by that rough measure a full six months later.    
      
   The second course of antibiotic administration produced a stronger effect.   
   “Even the one subject whose gut bacterial community fully recovered after   
   the first ciprofloxacin course experienced an incomplete recovery after the   
   second one,” said Relman.    
   The communities in the other two subjects partially recovered from the second   
   course, but never returned to their original state. In essence, each   
   subject’s community of gut-dwelling microbes shifted to a new,   
   “alternative” state and remained in    
   that state for at least two months after the second antibiotic course had been   
   completed. Thus, all three subjects experienced significant and lasting   
   changes in the specific membership of their internal microbial communities at   
   the end of the 10-month    
   study period.    
      
   “Ecologists have found that an ecosystem, such as a wildlife refuge, that is   
   quite capable of rebounding from even huge occasional perturbations — forest   
   fire, volcanic eruption, pests — may yet be undone by too rapid a series of   
   such perturbations,   
   ” said Les Dethlefsen, PhD, a research scientist in Relman’s lab and the   
   study’s first author. “In the same way, recurring antibiotic use may   
   produce a cumulative effect on our internal microbial ecosystems with   
   potentially debilitating, if as    
   yet unpredictable, consequences.”    
      
   “It’s as if your beneficial bacteria ‘remember’ the bad things done to   
   them in the past,” said Relman. “Clinical signs and symptoms may be the   
   last thing to show up.”    
      
      
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