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Primary Care Corner with Geoffrey Modest MD: Longterm Microbiome Changes with Antibiotics

3 Dec, 15 | by EBM

By Dr. Geoffrey Modest

A small study was done looking at antibiotic exposure and changes in both the salivary and gut microbiomes (see http://mbio.asm.org/content/6/6/e01693-15.full.pdf+html, or  doi:10.1128/mBio.01693-15​). This study involved 2 clinical sites, one in Sweden and one in the UK, randomly assigned to placebo vs different antibiotics, and looking at changes in the microbiomes both before a single antibiotic exposure and for up to one year after.

Details:

  • 30 people in the Swedish site were randomized to placebo, ciprofloxacin, or clindamycin; 44 people in the UK were randomized to placebo, amoxicillin, or minocycline (dosage not stated).
  • For the Swedish site:
    • The fecal microbiome diversity was significantly reduced for up to 4 months in the clindamycin group, and up to 12 months in the ciprofloxacin group.
    • The salivary microbiomes in the same groups showed only a short-term reductions in diversity and only immediately after the clindamycin or ciprofloxacin exposure.
  • For the UK site:
    • ​There was a significant reduction in microbiome diversity in both the fecal and saliva samples only at the 1 week samples after the minocycline exposure, which resolved by the 1 month analysis. Amoxicillin was not associated with any change in the microbiome in saliva or the gut.
  • The changes in the microbiome were largely a reduction in the production of the short-chain fatty acid butyrate in the gut, especially by clindamycin and ciprofloxacin, and butyrate production has the positive effect of inhibiting inflammation, carcinogenesis and oxidative stress in the gut. (Butyrate production was decreased in correspondence to the decreased gut population of many different bacterial species, such as Faecalibacterium, — see the article for the details).
  • Prior to antibiotic exposure they detected antibiotic resistant genes in both the saliva and gut microbiomes, even in this healthy population.

So, it is unclear why the 2 microbiomes behaved differently, with the salivary microbiome being minimally affected and quite resilient and the gut microbiome having prolonged changes of up to a year after a single exposure to antibiotics (ciprofloxacin being the worst of those studied). However, this type of study reinforces the need to minimize antibiotic usage (also reinforced by the presence of antibiotic resistant genes evident in the gut of these healthy volunteers even prior to the antibiotics), and preferentially to use ​antibiotics which have lesser microbiome effects (in this case, penicillins). One wonders if there is a “tipping-point” of repeated broad-spectrum antibiotic administration leading to more permanent changes in the microbiome.

See http://blogs.bmj.com/ebm/category/microbiome/ for an array of prior blogs on the microbiome;  http://blogs.bmj.com/ebm/2015/08/03/primary-care-corner-with-geoffrey-modest-md-antibiotic-overprescribing-2/ about antibiotic overprescribing; and http://blogs.bmj.com/ebm/2015/02/28/primary-care-corner-with-geoffrey-modest-md-pharyngitis-and-fusobacterium/​ which argues that penicillin is the drug-of-choice for pharyngitis, over azithromycin.​

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