Out of the Microscope and Into the Spotlight: Reconsidering the Role of the Microbiome and Antibiotics as a Risk Factor for Chronic Disease

GABRIELA RUIZ-COLÓN

Over the past year, microorganisms have made headlines for their role in causing vicious epidemics. Last year’s Ebola outbreak and the ongoing Middle East Respiratory Syndrome (MERS) flare in South Korea have become a source of public concern. However, not all microbes cause disease.  In fact, growing evidence suggests that our endemic bacteria—the human microbiome—may play a crucial role in modulating the course of disease. So, when we alter our microbiome, we become more susceptible to various chronic diseases.

One piece of evidence for this phenomenon comes from a recent study by Ben Bourssi and his colleagues at the University of Pennsylvania’s Perelman School of Medicine. (1) In this study, published by the European Journal of Endocrinology, Boursi and his collaborators sought to understand if there was an association between antibiotic use and risk of Type 2 Diabetes Mellitus (T2DM). Infectious disease professionals have warned us about the consequences of widespread antibiotic use for some time: for example, there is growing concern over the extremely drug-resistant strain of tuberculosis, XDR-TB, that may have developed as a result of antibiotic use and misuse. (2) But a new theory suggests that antibiotics can alter the composition of the gut microbiome in a way that contributes to T2DM and other chronic diseases and other chronic diseases. (3) This hypothesis is based on the fact that over time, humans have evolved symbiotic—mutually beneficialrelationships with gut microbes that facilitate crucial physiological processes. Accordingly, a microbiome is considered healthy when it has the proper variety of microbes to permit normal digestive, immune and neurological functions, among others. (3) Growing evidence reveals that a disruption of this symbiotic state can be a marker of chronic diseases, including T2DM. (4)

Escherichia coli lives in our gut and helps with tasks like digestion. Image via Wikimedia Commons, Creative Commons Attribution.

The authors used a measurement known known as an odds ratio (OR) to quantitatively explore whether antibiotic exposure is associated with increased risk of T2DM. They examined the medical records of more than 200,000 diabetic cases and more than 800,000 controls, and adjusted their results for factors like age, sex and smoking habits. (1) They found that risk of T2DM was not associated with a single dose of antibiotic administration, but was associated with the administration of two to five antibiotic courses. These antibiotics came from commonly used classes like  penicillin and quinolones, an antibiotic type that can treat hospital-borne infections. The authors did not find similar results with the administration of anti-viral and anti-fungal drugs. This suggests that an antibiotic-modulated change in the gut microbiome contributed to an increased risk of chronic disease. This is particularly important for patients who are pre-diabetic, as these individuals are more susceptible to skin, lower respiratory and urinary tract infections, thus warranting further antibiotic doses.

…a new theory suggests that antibiotics can alter the composition of the gut microbiome in a way that contributes to T2DM and other chronic diseases and other chronic diseases.

Boursi’s work joins other studies that have documented an association between the increased risk of chronic disease  and high antibiotic use. Crohn’s disease is one example.  Like T2DM and obesity, Crohn’s disease is characterized by an altered gut microbiome. This alteration may, in many cases, be induced by antibiotics. (7)

Antibiotics have fought off infectious diseases that took countless lives throughout centuries, but it is important to consider the looming threat of antibiotic overuse: the development of new antibiotic-resistant bacterial strains and now, greater susceptibility to chronic diseases. While transmissible diseases presented great challenges for medical professionals up until the development of vaccines in the mid-twentieth century, (8) chronic diseases plague our nation now. The studies discussed in this article suggest that misuse and overuse of antibiotics can fuel the chronic disease crisis by disturbing our most precious ecosystem: our microbiome.

Works Cited:

  1. Boursi, Ben, et al. “The effect of past antibiotic exposure on diabetes risk.” European Journal of Endocrinology 172.6 (2015): 639-648.
  2. “Drug-Resistant TB.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 01 Apr. 2014. Web.
  3. Brown, Kirsty, et al. “Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease.” Nutrients 4.8 (2012): 1095-1119.
  4. Li, Min, et al. “Symbiotic gut microbes modulate human metabolic phenotypes.” Proceedings of the National Academy of Sciences 105.6 (2008): 2117-2122.
  5. Qin, Junjie, et al. “A metagenome-wide association study of gut microbiota in type 2 diabetes.” Nature 490.7418 (2012): 55-60.
  6. Szumilas, Magdalena. “Explaining Odds Ratios.” Journal of the Canadian Academy of Child and Adolescent Psychiatry 19.3 (2010): 227–229. Print.
  7. Ungaro, Ryan, et al. “Antibiotics associated with increased risk of new-onset Crohn’s disease but not ulcerative colitis: a meta-analysis.” The American Journal of Gastroenterology 109.11 (2014): 1728-1738.
  8. Wright, Emily K., et al. “Recent Advances in Characterizing the Gastrointestinal Microbiome in Crohn’s Disease: A Systematic Review.” Inflammatory bowel diseases 21.6 (2015): 1219-1228.

Gabriela Ruiz-Colón is a staff writer for Brevia. She can be reached at gruizcolon@college.harvard.edu.