The Collateral Damage of Antibiotics

This post was written by Sean Gibbons, a Postdoctoral Associate in the Center for Microbiome Informatics and Therapeutics.

A close-up of capsules lined up in rows

Our bodies are complex ecosystems, like a rainforest or a coral reef, composed of thousands of species and trillions of cells. Human cells are just a fraction of this tangled web. A menagerie of bacteria, archaea, protists, fungi, and viruses are integral to the proper functioning of our bodies. Modern healthcare has focused on seeking out and destroying a few rogue microorganisms that are known to cause acute disease. Over the past 75 years, the means of microbial destruction – antibiotics – have saved countless lives. However, antibiotics also cause widespread collateral damage to our commensal microbiota (Dethlefsen et al 2008) and are often over-prescribed or misused. The negative consequences of systemic antibiotic usage appear to be coming back to haunt us, with increasing levels of antibiotic resistance, hospital-acquired infections, immune disorders, and other pathologies linked to a depauperate microbial community.

 

Although awareness about the importance of our indigenous microbes is growing, there are only a handful of studies concerning the impact of antibiotics on the human microbiome (Dethlefsen et al 2008, Dethlefsen and Relman 2011, Rashid et al 2015). A recent large-scale study in mBio looked at the influence of four different antibiotics on microbial communities in saliva and stool from two populations of healthy adults in the UK and in Sweden (66 patients in total) over the course of a year (Zaura et al 2015). Similar to prior work, they found that most antibiotics drove community-wide shifts in the both the gut and salivary microbiome. However, they showed that these changes persisted for up to a year in the gut, while oral microbial communities generally recovered within a month. Thus, our gut microbes appear to be much less resilient to antibiotic perturbations than our oral microbes. In particular, the study found that many anaerobic, spore-forming organisms (i.e. clostridia) tended to die off in response to clindamycin and ciproflaxin treatments. These butyrate-producing clostridia are thought to be important keystone species in maintaining intestinal health (Flint et al 2012). Recent work has shown that the loss of certain clostridia in the gut may increase susceptibility to infection by opportunistic pathogens like Clostridium difficile (Schubert et al 2015).

 

Based what we now know about the impact of antibiotics on the gut microbiome we should move towards a more ecological perspective in treating disease. We must recognize the importance of commensal microbial communities in maintaining our health. Antibiotics are essential tools for treating disease, but we should to be wary the ecological consequences of their use. By frequently weakening our commensal microbial communities, we leave open niches for opportunistic or invasive pathogens to gain a foothold. You cannot burn down a forest over and over again and expect it to bounce back. The weeds will rise! Therefore, future antibiotic treatments should be paired with pre- and pro-biotics designed to remediate our degraded guts.

 

sean_gibbons1Sean Gibbons is a Postdoctoral Associate working in the Center for Microbiome Informatics and Therapeutics. When not studying the dynamics of human gut microbial communities, Sean likes to frolic in the woods. You can learn about his science here.

 

References

Dethlefsen L, Huse S, Sogin ML, Relman DA (2008). The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS biol 6: e280.

Dethlefsen L, Relman DA (2011). Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proceedings of the National Academy of Sciences 108: 4554-4561.

Flint HJ, Scott KP, Louis P, Duncan SH (2012). The role of the gut microbiota in nutrition and health. Nature Reviews Gastroenterology and Hepatology 9: 577-589.

Rashid M-U, Zaura E, Buijs MJ, Keijser BJ, Crielaard W, Nord CE et al (2015). Determining the Long-term Effect of Antibiotic Administration on the Human Normal Intestinal Microbiota Using Culture and Pyrosequencing Methods. Clinical Infectious Diseases 60: S77-S84.

Schubert AM, Sinani H, Schloss PD (2015). Antibiotic-induced alterations of the murine gut microbiota and subsequent effects on colonization resistance against Clostridium difficile. mBio 6: e00974-00915.

Zaura E, Brandt BW, de Mattos MJT, Buijs MJ, Caspers MP, Rashid M-U et al (2015). Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces. mBio 6: e01693-01615.

 

Top