Antibiotics are Altering our Guts—Likely Permanently

 

Antibiotics are overused for conditions they do not treat, such as viral infections like cold or flu. Antibiotic overuse is leading to antibiotic resistance, one of the major challenges facing medicine today. But antibiotic resistance is not the only consequence of the average 10 – 20 courses of antibiotics children receive by the age of 18. An under-appreciated negative effect of too many antibiotics is the killing of beneficial bacteria, as highlighted in the recent Nature journal article, “Antibiotic Overuse: Stop the Killing of Beneficial Bacteria.”1

From the article, written by Martin M. Blaser, head of the department of medicine at New York University’s Langone Medical Center:

“Early evidence from my lab and others hints that, sometimes, our friendly flora never fully recover [after antibiotics]. 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 fueling 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.”

This gut microbiota alteration is likely a contributing factor to the increase in antibiotic resistance seen in such “superbugs” as Clostridium difficile and methicillin-resistant Staphylococcus aureus, Blaser further explained.

Studies by Les Dethlefsen, David Relman, et al, have also found permanent alterations in gut microbiota after antibiotic treatment. These researchers investigated the effects of ciprofloxacin on gut microbiota changes over a period of 8 to 10 months in two studies—one with two courses of antibiotic treatment, the other with one.2,3 Each study involved extensive stool sample analysis by 16S pyrosequencing (one rDNA, one rRNA) in three subjects over many months.

In one study, gut composition closely resembled its pretreatment state four weeks after antibiotic treatment. However, several bacterial groups did not recover even six months later. In the second study, gut composition stabilized by the end of 10 months, but it differed from its original state. The study concluded, “Antibiotic perturbation may cause a shift to an alternative stable state, the full consequences of which remain unknown.”

Blaser recommends reducing antibiotic use during pregnancy and childhood, citing that between one-third and one-half of pregnant women receive antibiotics during pregnancy in the U.S. and developing countries. “Each generation could be beginning life with a smaller endowment of ancient microbes than the last,” he stated, “Particularly the 30 percent or so of infants born via Cesarean.”

The search for effective alternatives to traditional antibiotics is on, as researchers from all over the world are testing new possibilities in the hopes of heading off the antibiotic-resistance disaster at the pass. One recent study highlighted the use of a commensal E. coli strain which was re-engineered  by adding fragments of DNA to the bacterium that allows it to sense the presence of the pathogenic bacteria known as, Psuedomonas aerugenosa. Pseudomonas is a superbug responsible for infections in the lungs, urinary tract, blood, and on wounds and burns. Upon sensing the Pseudomonas pathogen, the E coli released a potent toxin which killed up to 90% of the pathogen.4 It will be exciting to see if this technology holds up in forthcoming animal and human trials.

I believe the future will likely include widespread use of large amounts of commensal bacteria, probiotic bacteria and prebiotics, as well as genetically altered bacteria, to manage bacterial infections. We may even have a whole armamentarium of slightly altered commensal/probiotic bacteria on hand for certain infections. Antibiotics are already assuming a lesser role, and the CDC has a major program to remind physicians to be more discriminating in antibiotic use.5 So perhaps the future of pharmaceutical antibiotics will be their judicious use, in combination with various bacterial therapies, and this will become the standard of care. It will be very interesting to watch the unfolding of all the new research.

References

  1.  Blaser M, “Antibiotic overuse: Stop the killing of beneficial bacteria.” Nature. 2011 Aug 24;476(7361):393-4.
  2. Dethlefsen L, et al., “The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing.” PLoS Biol. 2008 Nov 18;6(11):e280.
  3. Dethlefsen L and Relman DA, “Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation.” PNAS. 2011 Mar 15;108 (Suppl 1):4554-4561.
  4. Saedi N, et al., “Engineering microbes to sense and eradicate Psuedomonas aeruginosa, a human pathogen.” Mol Sys Biol. 2011 Aug 16;7, no 521. Online ahead of print.
  5. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6034a1.htm
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