Editors' ChoiceMicrobiome

Just a Spoonful of Drug Makes Diversity Go Down

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Science Translational Medicine  18 Jan 2012:
Vol. 4, Issue 117, pp. 117ec10
DOI: 10.1126/scitranslmed.3003696

In their “Get Smart For Health Care” campaign, the U.S. Centers for Disease Control and Prevention targets inappropriate use of antibiotics, citing that up to 50% of uses in hospitals alone are unnecessary. In addition to lessening cost, reducing unnecessary antibiotic use decreases antimicrobial resistance and Clostridium difficile infections (CDIs). This nosocomial pathogen is linked to prior antibiotic exposure and causes a spectrum of diarrheal diseases from mild illness to fatal pseudomembranous colitis. Antibiotics—and clindamycin is especially notorious—may promote CDIs by disrupting the normal homeostasis of resident bowel flora, killing some bacteria while letting others flourish. But little is known about the mechanisms behind this shift and the subsequent emergence of C. difficile. Now, in a mouse model, Buffie and colleagues use a genetic amplification aproach to assess changes in intestinal microbial composition after a single dose of clindamycin and find that the drug reduces microbial diversity and renders mice susceptible to CDIs.

Mice that received clindamycin before an oral challenge of C. difficile were more susceptible to disease and died at a higher rate relative to control animals. In addition, among mice that survived bacterial challenge, those treated with clindamycin retained toxin-producing C. difficile in their guts at 28 days along with postinfectious histological changes consistent with damage to the cecum and ileum. Using a technique known as 16S ribosomal RNA genetic amplification to assess the microbial composition of the ileum and cecum, the authors demonstrated that mice not exposed to clindamycin had similar microbial diversity whether or not they had received a C. difficile oral challenge. In contrast, mice treated with clindamycin had significant and contracted changes in microbial diversity that lasted at least 4 weeks. The investigators also showed that mice that had been treated with clindamycin were susceptible to CDIs for at least 10 days after C. difficile exposure.

The new work reveals that a loss of microbial diversity from the cecal and ileal reservoirs after antibiotic administration has long-term consequences in terms of CDI risk, at least in mice. Using this model system, researchers have an opportunity to identify residual members of the gut microbiota that play a role in C. difficile “resistance” and how protective microbial populations may be preserved in the face of ongoing antibiotic pressure.

C. G. Buffie et al., Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile–induced colitis. Infect. Immun. 80, 62–73 (2012). [Abstract]

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